Distribution by Scientific Domains
Distribution within Medical Sciences

Kinds of Karyotype

  • abnormal karyotype
  • complex karyotype
  • male karyotype
  • normal karyotype
  • xy karyotype

  • Terms modified by Karyotype

  • karyotype analysis
  • karyotype result

  • Selected Abstracts

    A novel epidermal nevus syndrome with congenital cylindromatous turban tumor

    Jacinto J. Regalado
    Background:, Epidermal nevi (in the broad sense of epithelial nevi) may give rise to benign or malignant skin tumors. They may also be associated with anomalies of other organ systems in an epidermal nevus syndrome. Results:, This article describes a preterm infant with nevus sebaceus of the scalp and face, a large turban tumor with features of malignant cylindroma and multiple non-cutaneous defects. These included skeletal, hematopoietic, hepatobiliary, and urinary anomalies. Severe secondary lesions were present (pulmonary hypoplasia due to oligohydramnios; cerebral infarcts probably related to the turban tumor). Karyotype was normal, and family history was negative. Conclusions:, This unique case is unlike any reported epidermal nevus syndrome. Similarly, there is no prior report of a congenital cylindroma, certainly not as a turban tumor, which implies very rapid growth. The presence of both overgrowth and undergrowth phenomena (e.g. hypoplastic urinary tract and biliary atresia) may reflect dysregulation of paracrine growth factors, presumably due to genetic mutation. [source]

    Electrophoretic Karyotype of the Obligate Biotrophic Parasite Plasmodiophora brassicae Wor.

    H. Graf
    Classical genetic analysis is not possible with the protist Plasmodiophora brassicae due to the intracellular life of this obligate biotrophic parasite. An electrophoretic karyotype has been obtained using contour-clamped homogeneous electric field gel electrophoresis to facilitate gene mapping of P. brassicae. Using two different separation conditions 16 chromosomal bands of P. brassicae were distinguished ranging in approximate size from 2.2 Mb to 680 kb. According to this determination of chromosome number and size, the total genome size of P. brassicae was estimated to be 20.3 Mb. The chromosomal bands were further designated by their hybridization pattern with repetitive elements of P. brassicae. The repetitive element H4 (1800 bp) hybridized with 14 chromosomal bands, but the sequence of H4 showed no homology to known centromere or telomere structures and revealed no repetitive motifs. [source]

    Karyotype and cytogeography of the genus Heracleum (Apiaceae) in the Hengduan Mountains

    Xian-Lan DENG
    Abstract In the present study, the karyotypes of 34 populations belonging to 11 species and one variety of Heracleum from the Hengduan Mountains in China were examined. Chromosome numbers and the karyotypes of three species (H. souliei, H. kingdoni, and H. wenchuanense) are reported for the first time, as are the karyotypes of H. moellendorffii and H. henryi (tetraploid). Populations of H. candicans, H. franchetii, and H. kingdoni in the Hengduan Mountains were found to consist of a mixture of diploid and tetraploid plants. Except for four species of Heracleum, namely H. candicans, H. franchetii, H. henryi, and H. kingdoni, which have both diploid and tetraploid karyotypes, all other species of Heracleum are were found to be diploid. All karyotypes were found to belong to the 2A type of Stebbins, with the exception of H. candicans var. obtusifolium, which belongs to 2B, and H. hemsleyanum and H. franchetii (Mt. Dujuan, Daocheng, Sichuan, China), which belong to 1A. There was only a slight difference in the karyotype asymmetry index, which suggests a close kinship for species of Heracleum and that the entire phylogenetic development of Heracleum is relatively primitive. Species that exhibited advanced morphological features were also more advanced in karyotype structure, with the order of karyotype evolution being 1A,2A,2B. This phenomenon indicates that the species distributed in the Hengduan Mountains have not diverged completely and that the Hengduan Mountains are a relatively young and active area for the evolution of Heracleum. Polyploidization in Heracleum may be an important evolutionary mechanisms for some species, generating diversity. The biological attributes, distribution range, and the geological history of the genus have all played a part in accelerating the evolution through polyploidization or aneuploidization. It is known that as the distribution latitude of Heracleum decreases from north to south, the chromosome number, ploidy level, and asymmetry structure appear to increase. In the Hengduan Mountains, these tendencies are also evident. Finally, based on all the available cytogeographic data, we speculate that the more advanced tetraplont or aneuploid species of Heracleum in India may be derived from early diplont species that were distributed in the Caucasus region and Hengduan Mountains. The dispersal of Heracleum was from Eurasia to India, because this correlates with the emergence of the Himalayan Mountains through tectonic movement. Thus, the Hengduan Mountains are not only a center of diversity for Heracleum, but also a center of active speciation in modern times. [source]

    Karyotype and mitochondrial 16S gene characterizations in seven South American Cichlasomatini species (Perciformes, Cichlidae)

    O. Marescalchi
    Abstract The family Cichlidae constitutes most of the freshwater fish fauna of South America; its taxonomy is at present mainly based on morphological characters. Here, relationships among seven Cichlasomatini species have been investigated by studying their karyotype structure and by sequencing a 520 bp fragment of the mitochondrial 16S gene. Molecular data sets point to a high affinity of Cichlasoma amazonarum with Aequidens sensu stricto group, in particular with Aequidens tetramerus. Aequidens never form a single monophyletic clade: molecular trees group together ,Aequidens pulcher' and ,Aequidens rivulatus' and suggest their close relationship with Bujurquina and Laetacara, rather than with the A. sensu stricto group. Both molecular and karyotypic data confirm that Cleithracara maronii belongs to a distinct clade, thus supporting its generic differentiation based on morphological characters. Chromosome number, karyotype structure and molecular data suggest that Laetacara dorsigera is related to Bujurquina vittata and confirm their generic level of differentiation. From a cytotaxonomic point of view, a karyotype of 2n = 48 with most acrocentric or subacrocentric chromosomes could be the ancestral one from which the others might have derived. Zusammenfassung Ein großer Teil der südamerikanischen Süßwasserfische gehört zur Familie der Cichliden, deren Taxonomie bisher aber nur auf morphologischen Eigenschaften beruhte. In dieser Arbeit wurden die Verwandtschaftbeziehungen zwischen sieben Arten durch die Untersuchung des Karyotyps und eines 520 bp Teilstücks der mitochondrialen 16S rDNA-Sequenz studiert. Die molekularen Daten weisen auf eine höhere Verwandtschaft zwischen Cichlosoma amazonarum und Aequidens sensu strictu, besonders mit A. tetramerus, hin. Die Arten der Gattung Aequidens bilden niemals eine monophyletische Clade; die molekularen Bäume gruppieren immer A. pulcher und A. rivulatus zusammen und machen deren nähere Verwandtschaft zu den Gattungen Bujurquina und Laetacara wahrscheinlicher als zu der als Aequidens sensu strictu bezeichneten Gruppe. Die molekularen und die karyologischen Daten bestärken, daß die Art Cleithracara maroni einer klar getrennten Clade angehört, was auch die morphologischen Ergebnisses unterstützt. Die Chromosomenzahl, die Zusammensetzung des Karyotyps und die molekularen Vergleiche lassen erkennen, daßLaetacara dorsigera mit Bujurquina vittata verwandt ist, aber die Differenzierung den Gattungsstatus rechtfertigt. Vom cytotaxonomischen Standpunkt könnte ein Karyotyp mit 2n = 48 mit vorwiegend akrozentrischen oder subakrozentischen Chromosomen der ursprüngliche sein, von dem die anderen ableitbar sind. [source]

    Gene expression microarray analysis and genome databases facilitate the characterization of a chromosome 22 derived homogenously staining region

    Suzanna L. Arcand
    Abstract Karyotype and fluorescence in situ hybridization (FISH) analyses previously identified a homogenously staining region (HSR) derived from chromosome 22 in OV90, an epithelial ovarian cancer (EOC) cell line. Affymetrix® expression microarrays in combination with the UniGene and Human Genome Browser databases were used to identify the candidate genes comprising the amplicon of the HSR, based on comparison of expression profiles of OV90, EOC cell lines lacking HSRs and primary cultures of normal ovarian surface epithelial (NOSE) cells. A group of probe sets displaying a minimum 3-fold overexpression with a high reliability score (P-call) in OV90 were identified which represented genes that mapped within a 1,2 Mb interval on chromosome 22. A large number of probe sets, some of which represent the same genes, displayed no evidence of overexpression and/or low reliability scores (A-call). An investigation of the probe set sequences with the Affymetrix® and Sanger Institute Chromosome 22 Group databases revealed that some of the probe sets displaying discordant results for the same gene were complementary to intronic sequences and/or the antisense strand. Microarray results were validated by RT-PCR. Genomic analysis suggests that the HSR was derived from the amplification of a 1.1 Mb interval defined by the chromosomal map positions of ZNF74 and Hs.372662, at 22q11.21. The deduced amplicon is derived from a complex region of chromosome 22 that harbors low-copy repeats (LCRs). The amplicon contains 18 genes as likely targets for gene amplification. This study illustrates that large-scale expression microarray analysis in combination with genome databases is sufficient for deducing target genes associated with amplicons and stresses the importance of investigating probe set design before engaging in validation studies. © 2004 Wiley-Liss, Inc. [source]

    Cytogenetic analysis of pediatric anaplastic large cell lymphoma,

    PEDIATRIC BLOOD & CANCER, Issue 3 2010
    Lara Mussolin PhD
    Abstract Background Anaplastic large cell lymphoma (ALCL) constitutes approximately 15% of pediatric and 3% of adult non-Hodgkin lymphomas. Most pediatric cases harbor the reciprocal translocation t(2;5)(p23;q35), involving the alk gene. Cytogenetic studies of ALCL have mostly been published as case-reports. The aim of this study was to determine the cytogenetic profiles of a series of pediatric ALCL and to compare them with pediatric and adult ALCL from the literature. Methods Eighteen children treated at our Institution were studied by standard cytogenetic analysis and RT-PCR for the specific t(2;5) translocation product. Comparative analysis was performed on our findings and on the karyotypes of 48 pediatric and 39 adult ALCL reported in the literature. Results Karyotype was obtained in 16/18 ALCL: 9 showed translocation t(2;5) and 1 an alk variant form. Structural and numeric chromosomal abnormalities were identified in both pediatric and adult series. Trisomies were found preferentially in pediatric patients (P,=,0.013) and monosomies in adults (P,=,0.038). Trisomy 7 was found in 22% (13/59) of pediatric cases with abnormal karyotype and only in 5% (2/38) of adults; monosomy of chromosome 13 in 13% (5/38) of adults and only in 2% (1/59) of pediatric patients and monosomy of chromosome 15 in 16% (6/38) of adults and in none of the pediatric ALCL. Conclusion Our data suggest that pediatric and adult ALCL are characterized by different numerical chromosomal abnormalities. Larger prospective studies may elucidate their potential prognostic impact. Pediatr Blood Cancer. 2010;55:446,451. © 2010 Wiley-Liss, Inc. [source]

    Disease biology rather than age is the most important determinant of survival of patients , 60 years with acute myeloid leukemia treated with uniform intensive therapy

    CANCER, Issue 10 2005
    Vikas Gupta M.D.
    Abstract BACKGROUND The objectives of the current study were to evaluate the outcome of patients , 60 years with acute myeloid leukemia (AML) treated uniformly with high-dose daunorubicin containing induction and modified high-dose cytosine arabinoside containing postremission therapy, and to identify factors predictive of complete disease remission (CR) and survival. METHODS Between 1998 and 2002, the authors treated 117 newly diagnosed patients (acute promyelocytic leukemia excluded) with AML , 60 years (median, 67 years; range, 60,82 years). Karyotype (Medical Research Council classification) at diagnosis was categorized as good risk (n = 3), intermediate risk (n = 69), adverse risk (n = 26), and suboptimal/not done (n = 19). A normal karyotype was seen in 41 patients and 40 (34%) had secondary AML. RESULTS The outcome of induction included the following: CR, 62 (53%); early death, 5 (4%); death during hypoplasia, 14 (12%); and resistant disease, 36 (31%). The 3-year event-free (EFS) and overall survival (OS) rates were 9% (95% confidence interval [95% CI], 3,16%) and 17% (95% CI, 9,29%), respectively. In a univariate analysis, cytogenetics, lactate dehydrogenase level, leukocyte count, and performance status were the significant factors for EFS and OS. Age was not a significant prognostic factor for either CR or survival. In a multivariate model, adverse-risk cytogenetics, previous history of myelodysplastic syndrome or antecedent hematologic disorder, and high leukocyte count (> 30 × 109/L) were independent adverse prognostic factors for survival. The impact of adverse karyotype on EFS and OS was time dependent and was observed after 50 and 150 days, respectively. CONCLUSIONS The authors concluded that candidacy for intensive therapy in older patients should be based on biologic features of disease and fitness, rather than on age. Cancer 2005. © 2005 American Cancer Society. [source]

    Karyotype analysis and polyploidy in Palaua and a comparison with its sister group Fuertesimalva (Malvaceae)

    Abstract,Palaua (Malveae, Malvaceae) comprises 15 species endemic to the hyperarid coastal desert of Chile and Peru. So far, chromosome counts have been known for two diploid species (2n= 2x= 10) only. Here we report new chromosome numbers for 12 species of Palaua and four of its sister group Fuertesimalva. Karyotypes including 4,,6,-diamidino-2-phenylindole dihydrochloride (DAPI)/chromomycin (CMA3) fluorescent banding are presented for selected species representative of each of the main clades of Palaua. An important finding is the discovery of polyploids in one exclusively tetraploid species (P. trisepala) and four species with mixed diploid and tetraploid cytotypes (P. dissecta, P. mollendoensis, P. moschata, and P. tomentosa). The diploid and tetraploid karyotypes are all unimodal, symmetrical and show one or two pairs of satellite chromosomes with their associated CMA+/DAPI, band depending on the cytotype. For some of the tetraploids an autopolyploid origin is suggested. [source]

    Three different origins for apparent triploid/diploid mosaics

    PRENATAL DIAGNOSIS, Issue 7 2003
    Art Daniel
    Abstract Four apparent triploid/diploid mosaic cases were studied. Three of the cases were detected at prenatal diagnosis and the other was of an intellectually handicapped, dysmorphic boy. Karyotypes were performed in multiple tissues if possible, and the inheritance of microsatellites was studied with DNA from fetal tissues and parental blood. Non-mosaic triploids have a different origin from these mosaics with simple digyny or diandry documented in many cases. Three different mechanisms of origin for these apparent mosaics were detected: (1) chimaerism with karyotypes from two separate zygotes developing into a single individual, (2) delayed digyny, by incorporation of a pronucleus from a second polar body into one embryonic blastomere, and (3) delayed dispermy, similarly, by incorporation of a second sperm pronucleus into one embryonic blastomere. In three of the four cases, there was segregation within the embryos of triploid and diploid cell lines into different tissues from which DNA could be isolated. In case 2 originating by digyny, the same sperm allele at each locus could be detected in both triploid and diploid tissues, which is supportive evidence for the involvement of a single sperm and for true mosaicism rather than chimaerism. Similarly, in case 4 originating by dispermy, the same single ovum allele at each locus could be detected in diploid and triploid tissues, confirming mosaicism. In the chimaeric case (case 3), the diploid line had the karyotype 47,XY,+16 while the triploid line was 69,XXY. This suggests a chimaera, since, in a true mosaic, the triploid line should also contain the additional chromosome 16. Supporting the interpretation of a chimaeric origin for this case, the DNA data showed that the triploidy was consistent with MII non-disjunction (i.e. involving a diploid ovum). In the mosaic cases (1, 2, 4), there was no evidence of the involvement of a diploid sperm or a diploid ova, and in triploid/diploid mosaicism, an origin from a diploid gamete is excluded, since all such conceptuses would be simple triploids. In one of these triploid/diploid mosaics detected at prenatal diagnosis by CVS, the triploid line seemed to be sequestered into the extra-fetal tissues (confined placental mosaicism). This fetus developed normally and a normal infant was born with no evidence of triploidy in newborn blood or cord blood at three months of age. Copyright © 2003 John Wiley & Sons, Ltd. [source]

    Cytogenetics of species of Chamaecrista (Leguminosae , Caesalpinioideae) native to southern Brazil

    Chromosome numbers, karyotypes, meiotic behaviour and pollen analysis are presented for species of Chamaecrista Moench (Leguminosae, Caesalpinioideae, Cassieae) native to southern Brazil: C. nictitans ssp. patellaria, C. nictitans ssp. disadena, C. repens, C. rotundifolia, C. flexuosa, C. vestita and C. desvauxii. Meiotic behaviour is reported for the first time for all the taxa and was very regular; only bivalents were formed at diakinesis and metaphase I, chromosome disjunction and segregation were regular at anaphases I and II, meiotic indexes were over 99% and pollen fertility was over 92%. Pollen grains were subprolate in C. flexuosa and C. vestita and prolate,spheroidal in the other taxa. Karyotypes were symmetrical in all six species and the data are original, except for C. nictitans ssp. patellaria. Chromosome number is presented for the first time for C. repens (2n = 16) and has been confirmed for the other taxa: 2n = 14 for C. desvauxii, 2n = 32 for the tetraploid C. nictitans ssp. patellaria and C. nictitans ssp. disadena, and 2n = 16 for the other species. These two basic numbers found in the genus, x = 7 and x = 8, point to chromosome evolution by dysploidy, which has also been accompanied by polyploidy. © 2006 The Linnean Society of London, Botanical Journal of the Linnean Society, 2006, 150, 429,439. [source]

    Epigenetic abnormality of SRY gene in the adult XY female with pericentric inversion of the Y chromosome

    Tomoko Mitsuhashi
    ABSTRACT In normal ontogenetic development, the expression of the sex-determining region of the Y chromosome (SRY) gene, involved in the first step of male sex differentiation, is spatiotemporally regulated in an elaborate fashion. SRY is expressed in germ cells and Sertoli cells in adult testes. However, only few reports have focused on the expressions of SRY and the other sex-determining genes in both the classical organ developing through these genes (gonad) and the peripheral tissue (skin) of adult XY females. In this study, we examined the gonadal tissue and fibroblasts of a 17-year-old woman suspected of having disorders of sexual differentiation by cytogenetic, histological, and molecular analyses. The patient was found to have the 46,X,inv(Y)(p11.2q11.2) karyotype and streak gonads with abnormally prolonged SRY expression. The sex-determining gene expressions in the patient-derived fibroblasts were significantly changed relative to those from a normal male. Further, the acetylated histone H3 levels in the SRY region were significantly high relative to those of the normal male. As SRY is epistatic in the sex-determination pathway, the prolonged SRY expression possibly induced a destabilizing effect on the expressions of the downstream sex-determining genes. Collectively, alterations in the sex-determining gene expressions persisted in association with disorders of sexual differentiation not only in the streak gonads but also in the skin of the patient. The findings suggest that correct regulation of SRY expression is crucial for normal male sex differentiation, even if SRY is translated normally. [source]

    Increased immature hematopoietic progenitor cells CD34+/CD38dim in myelodysplasia

    CYTOMETRY, Issue 2 2006
    Mariela B. Monreal
    Abstract Background Myelodysplastic syndromes (MDS) are clonal disorders affecting hematopoietic progenitor cells (HPC). Despite the relevance of clonal CD34+ cells in developing MDS, only few studies analyze the phenotype of this cell population. The aim of this study was to evaluate phenotypic changes on HPC in MDS that could reflect abnormalities in the differentiation process of stem cells. Methods We analyzed the expression of CD38 and HLA-DR on CD34+ cells by flow cytometry in 36 patients with MDS, as well as in healthy donors (n = 12) and patients with other hematological disorders: non-Hodgkin lymphomas and multiple myeloma, both in complete remission (CR) (n = 32); acute lymphoblastic leukemia in CR (n = 17); de novo acute myeloblastic leukemia (AML) at diagnosis (n = 22) and in CR (n = 37); and AML secondary to MDS at diagnosis (n = 19). Cases with available karyotype were grouped according to the International Prognostic Scoring System (IPSS). Results Compared to normal BM, the fraction of immature HPC, characterized as CD34+bright, intermediate FSC/SSC, and CD38dim, was significantly increased in high risk MDS and secondary AML, but not in low risk MDS, (P , 0.001, P = 0.03, and P = 0.7). De novo AML showed decreased immature HPC. High numbers of immature HPC correlated with higher IPSS risk groups (P = 0.05) and showed significant impact on disease progression (P = 0.03). Conclusion Our study confirms that evaluation of CD38 expression pattern on HPC is an easy and reproducible test that allows evaluating the immature subset of progenitor cells. Increased immature HPC in high risk MDS and secondary AML may reflect blocked differentiation of CD34+ cells in these diseases. © 2006 International Society for Analytical Cytology [source]

    Acute exposure of human lung cells to 1,3-butadiene diepoxide results in G1 and G2 cell cycle arrest

    Michael Schmiederer
    Abstract 1,3-butadiene (BD) causes genetic damage, including adduct formation, sister chomatid exchange, and point mutations. Previous studies have focused on the types of genetic damage and tumors found after long-term exposure of rodents to butadiene. This study examined the effect of the most active BD metabolite, butadiene diepoxide (BDO2), on cell cycle entry and progression in human lung fibroblasts (LU cells) with a normal diploid karyotype. Serum-arrested (G0) LU cells were exposed to BDO2 for 1 hr and stimulated to divide with medium containing 10% fetal bovine serum. The BDO2 -treated LU cells were evaluated for cell cycle progression, nuclear localization of arrest mediators, mitotic index, and cellular proliferation. The BDO2 -treated cells demonstrated a substantial inhibition of cell proliferation when treated with 100 ,M BDO2 for 1 hr. No appreciable levels of apoptosis or mitotic figures were observed in the BDO2 -treated cells through 96 hr posttreatment. Flow cytometric analysis revealed that the lack of proliferation in BDO2 -treated LU cells was related to G1 arrest in about half of the cells and a delayed progression through S and G2 arrest in nearly all of the remaining cells. Both G1 and G2 arrest were prolonged and only a very small percentage of BDO2 -treated cells were eventually able to replicate. Increased nuclear localization of both p53 and p21cip1 was observed in BDO2 -treated cells, suggesting that the cell cycle arrest was p21cip1 -mediated. These results demonstrate that BDO2 induces cell cycle perturbation and arrest even with short-term exposure that does not produce other pathologic cellular effects. Environ. Mol. Mutagen., 2005. © 2005 Wiley-Liss, Inc. [source]

    Therapy-related leukemia following chemoradiotherapy for esophageal cancer

    Naoya Mimura
    Abstract Chemoradiotherapy has improved the outcome of patients with esophageal cancer. Although a sufficiently long-time survival has resulted in the increase of several treatment-related late toxicities, little is still known about the incidence of secondary malignancies. In our hospital, 348 patients with esophageal cancer received chemotherapy consisting of nedaplatin and 5-fluorouracil and concurrent irradiation. Median and average follow-up durations were 8 and 21 months (1,92), respectively. Four patients developed leukemia after 19,48 months of follow-up. Two patients were diagnosed with overt leukemia from myelodysplastic syndrome presenting a complex karyotype, including the deletion of chromosome 5 or 7. Notably, one patient showed an additional chromosomal abnormality with t(9;22)(q34;q11). Other patients developed acute myeloid leukemia with t(9;22)(q34;q11) and Burkitt leukemia with t(8;14)(q24;q32). All patients eventually succumbed to leukemia. Platinum and fluorouracil have shown relatively lower risks for secondary malignancies in comparison with alkylating agents and topoisomerase II inhibitors. Especially, nedaplatin has never been described to introduce secondary neoplasms. Our report supports the idea that the concurrent administration of radiotherapy with these agents affects the risk of leukemia. Interestingly, rare balanced chromosomal abnormalities were observed in the present cases, thus providing new insights into the leukemogenesis of therapy-related leukemia. [source]

    Chromosome 1 abnormalities in myeloid malignancies: a literature survey and karyotype,phenotype associations

    Domenica Caramazza
    Abstract Chromosome 1 is the largest human chromosome and contains over 1600 known genes and 1000 novel coding sequences or transcripts. It is, therefore, not surprising that recurrent chromosome 1 abnormalities are regularly encountered in both neoplastic and non-neoplastic medical conditions. The current review is focused on myeloid malignancies where we summarize the relevant published literature and discuss specific karyotype,phenotype associations. We show that chromosome 1 abnormalities are most frequent in BCR-ABL -negative classic myeloproliferative neoplasms (MPN): polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Specific abnormalities include duplications (e.g. 1q12,1q32 in PV, 1q21,32,1q32,44 in post-PV MF or PMF), deletions (e.g. 1p13,36,pter in PV or PMF, 1q21 in PMF) and unbalanced translocations involving chromosome 6, such as der(6)t(1;6)(q21,25;p21.3,23), and other partner chromosomes involving 1q10/1p11 and 1q21,25 breakpoints. Although occasionally seen in chronic phase MPN, unbalanced 1;7 translocations, e.g. der(1;7)(q10;p10), are usually seen in acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and post-MPN AML/MDS. These observations suggest that certain chromosome 1 regions, especially 1q21,1q32 and 1p11,13, might harbor oncogenes or tumor suppressor genes that are pathogenetically relevant to both chronic and advanced phases of MPN. [source]

    DV-ICE, intensive induction and early transplantation for adult patients with acute lymphoblastic leukemia: a phase II study

    Christine Dudler
    Abstract Objectives:, Eighty percent of adult patients with acute lymphoblastic leukemia (ALL) achieve a complete remission (CR) but only 30,40% are long term survivors. Best treatment strategies remain to be defined. The role of induction intensity, first remission hematopoietic stem cell transplantation (HSCT) and maintenance chemotherapy continues to be discussed. We tested a strategy of high intensity treatment of short duration followed by HSCT. Patients and methods:, This prospective phase II study used induction with DV-ICE followed by immediate allogeneic or autologous HSCT (depending on donor availability) without additional consolidation or maintenance treatment. DV-ICE consisted of dexamethasone, vincristine, idarubicin, etoposide, and conventional dose cytosine arabinoside; HSCT was planned immediately if CR was achieved or after an additional course of intermediate high dose cytosine arabinoside and etoposide for patients with induction failure. A total of 42 consecutive patients between 17 and 67 yr of age (median 43 yr) were enrolled. Of the 42 patients, 57% were male, 76% had B-lineage ALL, 19% T-lineage ALL and two patients biphenotypic ALL. 29% were Ph+; 7% had 11q23 and 45% had a normal karyotype. CNS involvement was found in three patients. Results:, Thirty-three patients (79%) achieved a CR, 24 patients after induction I or II and nine patients after rescue HSCT. 31 patients received a HSCT (seven autologous and 24 allogeneic). 11 patients did not receive a HSCT because of early death in nine (treatment toxicity in five, refractory disease in four), one patient refused transplantation, one patient was not suitable. Disease-free survival (DFS) of the entire cohort was 46% (95% CI ±16%) at 1 yr and 16% (±13%) at 5 yr. Overall survival (OS) was 63% (±15%) at 1 yr and 23% (±15%) at 5 yr, with a median follow-up of surviving patients of 55 (4,136) months. Neither disease subtype, cytogenetic abnormalities nor patient age or gender was significantly associated with survival. Conclusions:, Intensive induction using DV-ICE followed by early transplantation without treatment beyond 4 months failed to improve outcome compared with standard treatment. [source]

    Comprehensive analysis of cooperative gene mutations between class I and class II in de novo acute myeloid leukemia

    Yuichi Ishikawa
    Abstract Acute myeloid leukemia (AML) has been thought to be the consequence of two broad complementation classes of mutations: class I and class II. However, overlap-mutations between them or within the same class and the position of TP53 mutation are not fully analyzed. We comprehensively analyzed the FLT3, cKIT, N-RAS, C/EBPA, AML1, MLL, NPM1, and TP53 mutations in 144 newly diagnosed de novo AML. We found 103 of 165 identified mutations were overlapped with other mutations, and most overlap-mutations consisted of class I and class II mutations. Although overlap-mutations within the same class were found in seven patients, five of them additionally had the other class mutation. These results suggest that most overlap-mutations within the same class might be the consequence of acquiring an additional mutation after the completion both of class I and class II mutations. However, mutated genes overlapped with the same class were limited in N-RAS, TP53, MLL -PTD, and NPM1, suggesting the possibility that these irregular overlap-mutations might cooperatively participate in the development of AML. Notably, TP53 mutation was overlapped with both class I and class II mutations, and associated with morphologic multilineage dysplasia and complex karyotype. The genotype consisting of complex karyotype and TP53 mutation was an unfavorable prognostic factor in entire AML patients, indicating this genotype generates a disease entity in de novo AML. These results collectively suggest that TP53 mutation might be a functionally distinguishable class of mutation. [source]

    Conventional cytogenetics in myelofibrosis: literature review and discussion

    Kebede Hussein
    Abstract The clinical phenotype of myelofibrosis (MF) is recognized either de novo (primary) or in the setting of polycythemia vera (post-PV) or essential thrombocythemia (post-ET). Approximately one-third of patients with primary MF (PMF) present with cytogenetic abnormalities; the most frequent are del(20q), del(13q), trisomy 8 and 9, and abnormalities of chromosome 1 including duplication 1q. Other less frequent lesions include ,7/del(7q), del(5q), del(12p), +21 and der(6)t(1;6)(q21;p21.3). In general, cytogenetic abnormalities are qualitatively similar among PMF, post-ET MF and post-PV MF although their individual frequencies may differ. Based on prognostic effect, cytogenetic findings in MF are classified as either ,favorable' or ,unfavorable'. The former include normal karyotype or isolated del(20q) or del(13q) and the latter all other abnormalities. Unfavorable cytogenetic profile in both PMF and post-PV/ET MF confers an independent adverse effect on survival; it is also associated with higher JAK2V617F mutational frequency. In addition to their prognostic value, cytogenetic studies in MF ensure diagnostic exclusion of other myeloid neoplasms that are sometimes associated with bone marrow fibrosis (e.g. BCR-ABL1 -positive or PDGFRB -rearranged) and also assist in specific treatment selection (e.g. lenalidomide therapy is active in MF associated with del(5q). [source]

    Children and adults with acute lymphoblastic leukaemia have similar gene expression profiles

    E. Kuchinskaya
    Abstract:,Objectives:,To compare the gene expression pattern in children and adults with acute lymphoblastic leukaemia (ALL) in order to improve our understanding of the difference in disease biology and prognosis. Methods:,The gene expression profiles in diagnostic samples from 29 children and 15 adults with ALL were analysed using the oligonucleotide chip Hu95ver2a, produced by Affymetrix. Results:,Unsupervised hierarchical cluster analysis revealed that, in spite of differences in outcome, patients clustered irrespective of age, first by T-cell or B-precursor immunophenotype, and second by cytogenetic changes within the B-precursor group. The expression pattern analysis allowed the reclassification of some samples into the proper cytogenetic group. We also showed that separate clustering of samples with the BCR/ABL translocation could be explained by different breakpoint regions in the BCR. No significant difference in gene expression was observed between samples with and without CDKN2A deletion within the B-precursor group. Analysis of different age groups revealed a similarity in expression profiles when infants with the MLL translocation and adults over 40 yr of age were compared irrespective of karyotype. Conclusions:,In spite of the difference in clinical outcome, the gene expression pattern in children and adults with ALL is very similar and is primarily dependent on immunophenotype and cytogenetic aberrations. However, when age groups are compared, the expression patterns of infants and adults over 40 show a remarkable similarity. [source]

    Association of non-alcoholic steatohepatitis (NASH) with chronic neutrophilic leukemia

    Chikashi Yoshida
    Abstract: A 54-yr-old female having chronic neutrophilic leukemia (CNL) associated with severe liver injury is presented. Physical examination on admission showed severe jaundice, hepatosplenomegaly, massive ascites, and pretibial edema. Complete blood count showed a hemoglobin level of 9.1 g/dL, platelet count of 25.8 × 104/,L, and white blood cell count of 36.6 × 103/,L with 89.7% neutrophils. Blood chemistry showed hyperbilirubinemia (21.9 mg/dL) with normal transaminase levels. There was no abnormality in serum cholesterol, triglyceride, or glucose levels. Neutrophil alkaline phosphatase activity was significantly elevated. Bone marrow aspiration showed myeloid hyperplasia with normal karyotype. Rearrangement of the bcr/abl was not detected by either polymerase chain reaction or fluorescence in situ hybridization. Human androgen receptor gene assay (HUMARA) of the bone marrow cells showed clonal proliferation of neutrophils. The patient was diagnosed as having CNL. To evaluate the pathogenesis of the liver injury, a needle biopsy was performed, which showed steatohepatitis with infiltration of neutrophils. As the patient had no history of alcohol abuse, a diagnosis of non-alcoholic steatohepatitis (NASH) was made. Assuming that the infiltration of abnormal neutrophils into the liver contributed to the development of NASH, she was treated with cytoreductive chemotherapy (cytosine arabinoside: 100 mg/d, 1,3 doses/wk). With decreases in white blood cell counts, serum bilirubin levels decreased gradually to 1.5 mg/mL. A postchemotherapy liver biopsy specimen showed marked improvement of the fatty degenerative change. To our knowledge, this is the first report describing the development of NASH in a myeloproliferative disorder. We believe that the infiltration of leukemic cells contributed to the development of NASH in this patient. [source]

    Cytogenetic, FISH, and molecular studies in a case of B-cell chronic lymphocytic leukemia with karyotypic evolution

    Christian Chena
    Abstract:, We report the clinical, cytogenetic, fluorescence in situ hybridization (FISH) and molecular findings in a 54-yr-old male patient diagnosed with B-cell chronic lymphocytic leukemia (B-CLL), who showed progression to a diffuse large B-cell lymphoma (Richter's syndrome). Genetic studies were performed at diagnosis and during the Richter's transformation (RT). A clonal karyotype with two dicentric chromosomes, psu dic(12,21)(q24;q10) and dic(17,18)(p11.2;p11.2), was found. Both rearrangements were confirmed by FISH. Molecular cytogenetics analysis using p53 probe showed monoallelic loss of this tumor suppressor gene in 43.8% and 77.3% of cells for the first and the second studies, respectively). In both studies, deletions of D13S319 (18% and 12% of cells) and D13S25 loci (13% and 12% of cells) at 13q14 were found. Polymerase chain reaction analysis showed the MBR/JH rearrangement of the bcl-2 gene. FISH studies using LSI bcl-2/IgH probe allowed quantifying the clonal cell population with this rearrangement (4% and 6.6% of cells at diagnosis and RT, respectively). To our knowledge, this is the first case with a psu dic(12,21) described in B-CLL. The low percentage of cells with the 13q14 deletion and bcl-2/IgH rearrangement suggests that they were secondary events that resulted from clonal evolution. Our patient had a short survival (9 months) and a clear lack of response to several therapeutic agents, confirming the association of p53 gene deletion and karyotypic evolution with disease progression. [source]

    Turner syndrome and the evolution of human sexual dimorphism

    Bernard Crespi
    Abstract Turner syndrome is caused by loss of all or part of an X chromosome in females. A series of recent studies has characterized phenotypic differences between Turner females retaining the intact maternally inherited versus paternally inherited X chromosome, which have been interpreted as evidence for effects of X-linked imprinted genes. In this study I demonstrate that the differences between Turner females with a maternal X and a paternal X broadly parallel the differences between males and normal females for a large suite of traits, including lipid profile and visceral fat, response to growth hormone, sensorineural hearing loss, congenital heart and kidney malformations, neuroanatomy (sizes of the cerebellum, hippocampus, caudate nuclei and superior temporal gyrus), and aspects of cognition. This pattern indicates that diverse aspects of human sex differences are mediated in part by X-linked genes, via genomic imprinting of such genes, higher rates of mosaicism in Turner females with an intact X chromosome of paternal origin, karyotypic differences between Turner females with a maternal versus paternal X chromosome, or some combination of these phenomena. Determining the relative contributions of genomic imprinting, karyotype and mosaicism to variation in Turner syndrome phenotypes has important implications for both clinical treatment of individuals with this syndrome, and hypotheses for the evolution and development of human sexual dimorphism. [source]

    Prognostic significance of secondary cytogenetic alterations in follicular lymphomas

    Nathalie A. Johnson
    Follicular lymphoma (FL) is an indolent lymphoma with a long median survival. Transformation to a more aggressive histology (TLy) is a major cause of mortality. The critical events leading to TLy are unknown. We assessed the prognostic significance of secondary cytogenetic alterations on overall survival (OS) and transformation from 210 diagnostic FL biopsies. We analyzed serial and transformed karyotypes for recurrent alterations that predict transformation. Over 10 years, 31% of cases developed TLy. The only alteration in diagnostic karyotypes that correlated with an inferior OS was an additional X chromosome in males only (P = 0.005) suggesting that other mechanisms including epigenetic factors and over-expression of genes on the X chromosome may play a role in FL pathogenesis. In transformed karyotypes, 8q24 (MYC) translocations were common (14/37) and resulted in a median survival of 3 months posttransformation (P = 0.01). In serially obtained biopsies (28 pts), 43% of the later biopsies lacked the cytogenetic alterations found in the original FL karyotype, suggesting that karyotypic progression of FL is not strictly linear in all cases. Consequently, studying clonal evolution in FL using serial biopsies may not represent the full complexity of genetic alterations leading to transformation. © 2008 Wiley-Liss, Inc. [source]

    Identification of NUP98 abnormalities in acute leukemia: JARID1A (12p13) as a new partner gene

    Laura J. C. M. van Zutven
    Chromosome rearrangements are found in many acute leukemias. As a result, genes at the breakpoints can be disrupted, forming fusion genes. One of the genes involved in several chromosome aberrations in hematological malignancies is NUP98 (11p15). As NUP98 is close to the 11p telomere, small translocations might easily be missed. Using a NUP98 -specific split-signal fluorescence in situ hybridization (FISH) probe combination, we analyzed 84 patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia, or myelodysplastic syndrome with either normal karyotypes or 11p abnormalities to investigate whether there are unidentified 11p15 rearrangements. Neither NUP98 translocations nor deletions were identified in cases with normal karyotypes, indicating these aberrations may be very rare in this group. However, NUP98 deletions were observed in four cases with unbalanced 11p aberrations, indicating that the breakpoint is centromeric of NUP98. Rearrangements of NUP98 were identified in two patients, both showing 11p abnormalities in the diagnostic karyotype: a t(4;11)(q1?3;p15) with expression of the NUP98,RAP1GDS1 fusion product detected in a 60-year-old woman with AML-M0, and an add(11)(p15) with a der(21)t(11;21)(p15;p13) observed cytogenetically in a 1-year-old boy with AML-M7. JARID1A was identified as the fusion partner of NUP98 using 3, RACE, RT-PCR, and FISH. JARID1A, at 12p13, codes for retinoblastoma binding protein 2, a protein implicated in transcriptional regulation. This is the first report of JARID1A as a partner gene in leukemia. © 2006 Wiley-Liss, Inc. [source]

    Assessment by M-FISH of karyotypic complexity and cytogenetic evolution in bladder cancer in vitro

    Sarah V. Williams
    We carried out multiplex fluorescence in situ hybridization (M-FISH) and follow-up FISH studies on a large series of transitional cell carcinoma (TCC) cell lines and 2 normal urothelium,derived cell lines, several of which have not had karyotypes reported previously. M-FISH analysis, with appropriate follow-up, complements conventional cytogenetic analysis and array CGH studies, allowing a more accurate definition of karyotype. The detailed karyotypic data obtained will assist in choosing suitable cell lines for functional studies and identifies common losses, gains, breakpoints and potential fusion gene sites in TCC. We have shown changes in cell lines RT112 and DSH1 following prolonged culture, and differences in karyotype, between RT112 cultures obtained from different sources. We propose a model for the evolutionary changes leading to these differences. A comparison with the literature found other examples of differences in cell-line karyotypes between different sources. Nevertheless, several karyotypic changes were preserved between different sources of the same cell line and were also seen in more than one cell line. These may be the most important changes and include ,8p, +20, 4q,, 10p,, 16p, and breaks in 8p21. We carried out a more detailed follow-up of some regions, which showed involvement of 8p breaks and losses in 15 of 16 TCC cell lines but in neither of the normal urothelium,derived cell lines. Some changes represented distal loss, whereas others were small deletions. Further study of this region is warranted. Supplementary material for this article can be found on the Genes, Chromosomes and Cancer website at http://www.interscience.wiley.com/jpages/1045-2257/suppmat/index.html. © 2005 Wiley-Liss, Inc. [source]

    MLL/GRAF fusion in an infant acute monocytic leukemia (AML M5b) with a cytogenetically cryptic ins(5;11)(q31;q23q23)

    Ioannis Panagopoulos
    More than 30 fusions involving the MLL gene at 11q23 have been reported in acute myeloid leukemia (AML). Some of these chimeras are rather common, such as MLL/MLLT3(AF9), but many are quite rare, with some, for example, MLL/GRAF, described only in a single case. The MLL/GRAF fusion, in which the reciprocal hybrid was not expressed, suggesting that the former transcript was the leukemogenic one, was detected in a juvenile myelomonocytic leukemia with a t(5;11)(q31;q23). Here, we report a second case,an infant acute monocytic leukemia (AML M5b),with an MLL/GRAF fusion. By conventional G-banding, the karyotype was normal. However, Southern blot and fluorescence in situ hybridization analyses revealed that MLL was rearranged and that the 5, part of the MLL gene was inserted into 5q in the vicinity of 5q31, which harbors GRAF. Reverse-transcriptase polymerase chain reaction (PCR) showed that exon 9 of MLL was fused in-frame with exon 19 of GRAF. Extralong genomic PCR with subsequent sequence analysis demonstrated that the breakpoints occurred in intron 9 of MLL, nine base pairs (bp) downstream from exon 9, and in intron 18 of GRAF, 117 bp downstream from exon 18. A 6-bp insertion (ACACTC) of unknown origin was present at the junction. The putative MLL/GRAF fusion protein would retain the AT-hook DNA-binding domain, the DNA methyl transferase motif, the transcription repression domain of MLL, and the SH3 domain of GRAF. As expected, the reciprocal GRAF/MLL was neither expressed nor generated at the genomic level as a consequence of the ins(5;11)(q31;q23q23). On the basis of the now-reported two cases with MLL/GRAF, we conclude that this transcript,but not the reciprocal one,characterizes a rare genetic subgroup of infant AML. © 2004 Wiley-Liss, Inc. [source]

    Comparative expressed sequence hybridization studies of high-hyperdiploid childhood acute lymphoblastic leukemia

    Alicja M. Gruszka-Westwood
    The functional consequences of a high-hyperdiploid karyotype, found in up to one-third of cases of acute lymphoblastic leukemia (ALL), are unknown. Using the technique of comparative expressed sequence hybridization (CESH), we sought to address the question of whether increased chromosome copies in hyperdiploid ALL lead to increased gene expression. Relative expression of hyperdiploid ALL blasts versus peripheral blood mononuclear cells was analyzed in 18 patients. Common regions of overexpression corresponding to the presence of tri-/tetrasomies included: Xp22.1,22.2, 4q28, 6q14,15, 6q24, 10p13, 14q23,24, 17q21, 18q12, and 21q21, identified in 28,89% of cases. However, increased expression without underlying trisomy occurred at 3p21.3, 7q11.2, 8p21, and 8q24.1 in 39,90% of cases. High expression at 7q11.2, the most consistent change detected, was confirmed by quantitative PCR. Poor correlation between the presence of tri-/tetrasomy and overexpression was observed for chromosomes 14 and 17. Two cases were reanalyzed versus (i) B cells, (ii) transformed B cells, and (iii) CD34+19+ cells (the putative counterpart of the leukemic cell). A reduction in the number of relatively overexpressed regions was observed with CD34+19+ cells. In particular, the peak at 7q11.2 disappeared, suggesting up-regulation of genes from this region in the early ontology of normal B-cell development. In conclusion, we have shown that tri-/tetrasomies in hyperdiploid ALL lead to an increase in the expression of associated sequences. The choice of a biologically relevant reference is crucial for data interpretation. © 2004 Wiley-Liss, Inc. [source]

    Order of genetic events is critical determinant of aberrations in chromosome count and structure

    Christine Fauth
    A sequential acquisition of genetic events is critical in tumorigenesis. A key step is the attainment of infinite proliferative potential. Acquisition of this immortalization requires the activation of telomerase in addition to other activities, including inactivation of TP53 and the retinoblastoma family of tumor-suppressor proteins. However, the importance of the order in which these genetic events occur has not been established. To address this question, we used a panel of normal mammary fibroblasts and endothelial cultures that were immortalized after transduction with the catalytic subunit of telomerase (hTERT) and a temperature-sensitive mutant of the SV40 large-tumor (tsLT) oncoprotein in different orders in early- and late-passage stocks. These lines were maintained in continuous culture for up to 90 passages, equivalent to >300 population doublings (PDs) post-explantation during 3 years of continuous propagation. We karyotyped the cultures at different passages. Cultures that received hTERT first followed by tsLT maintained a near-diploid karyotype for more than 150 PDs. However, in late-passage stocks (>200 PDs), metaphase cells were mostly aneuploid. In contrast, the reverse order of gene transduction resulted in a marked early aneuploidy and chromosomal instability, already visible after 50 PDs. These results suggest that the order of genetic mutations is a critical determinant of chromosome count and structural aberration events. © 2004 Wiley-Liss, Inc. [source]

    Comparative analysis of MLL partial tandem duplication and FLT3 internal tandem duplication mutations in 956 adult patients with acute myeloid leukemia

    Christine Steudel
    Partial tandem duplication (PTD) of the MLL gene and internal tandem duplication (ITD) of the juxtamembrane region of the FLT3 receptor tyrosine kinase gene have been described in acute myeloid leukemia (AML) patients, preferentially in those with normal cytogenetics. These alterations have been associated with a poor prognosis. In our study, we analyzed the prevalence and the potential prognostic impact of these aberrations in a large unselected and well-defined cohort of 956 patients with AML. Results were correlated with cytogenetic data and clinical outcome. MLL PTD was detected by RT-PCR, subsequent nucleotide sequencing, and Southern blotting. The overall incidence was found to be 5.0% (48/956), whereas FLT3 ITD was detected in 19.2% (184/956). Sixteen cases were positive for both alterations. The rate of MLL PTD in FLT3 ITD positive patients was significantly higher than that in FLT3 ITD negative patients [16/184 (8.7%); 32/772 (4.1%); P = 0.025]. However, both aberrations were highly increased in patients with normal karyotype (MLL PTD 35/431, P = 0.004; FLT3 ITD 132/334, P < 0.001). When restricted to this subgroup, the rate of MLL PTD in patients with FLT3 mutations was not significantly increased. No statistically significant differences were detected between patients positive for MLL PTD and patients negative for MLL PTD in the rate of complete remissions or the overall survival, although we did see a significantly shorter disease-free survival in patients age 60 or younger. In conclusion, although there is an overlap in the mutational spectrum in AML with FLT3 ITD and MLL PTD mutations, our data do not support a common mechanistic basis. Although associated with inferior disease-free survival, the results of this study do not unequivocally support the notion that MLL PTD mutations represent an independent prognostic factor. © 2003 Wiley-Liss, Inc. [source]

    Spectral karyotyping in patients with acute myeloid leukemia and a complex karyotype shows hidden aberrations, including recurrent overrepresentation of 21q, 11q, and 22q

    Krzysztof Mrózek
    We used spectral karyotyping (SKY) to study 29 adults with acute myeloid leukemia and a complex karyotype containing one to nine abnormalities that were not fully identifiable by G-banding. SKY showed the origin of rings and unidentified material in unbalanced translocations in all cases and the origin of markers in most, allowing reinterpretation of 136 aberrations and discovery of three aberrations hidden in normal chromosomes. SKY confirmed 10 and refined the interpretation of three balanced aberrations recognized by G-banding and identified another nine balanced aberrations, including a novel translocation involving the RUNX1 gene. Eleven of 32 deletions found by G-banding were shown to be cryptic translocations or insertions, including three of four chromosome 3 deletions, two of three del(7q), and two of 12 del(5q). Of the 92 chromosomes deemed lost entirely by G-banding, 63 (68%) were shown to be involved in structural aberrations. This was especially true for ,21 (eight of eight patients), ,5 (five of six patients), ,20 (seven of nine patients), and ,18 (six of 12 patients). Unexpectedly, SKY uncovered a hidden overrepresentation of segments from at least one chromosome in 21 patients. The most frequently overrepresented was 21q, found in eight patients, including four with high-level 21q amplification. Fluorescence in situ hybridization showed that the RUNX1 gene was not the target of amplification in seven of these patients. Also frequently gained were 11q (in seven patients, including three with high-level MLL gene amplification) and 22q (in seven patients). We conclude that SKY considerably enhances the accuracy of karyotype interpretation, and that amplification of chromosomal material may play a greater role in leukemogenesis than has been recognized. © 2002 Wiley-Liss, Inc. [source]