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Myelodysplastic Syndromes (myelodysplastic + syndromes)

Distribution by Scientific Domains
Medical Sciences91%
Life Sciences8%
Distribution within Medical Sciences
Hematology63%
Oncology & Radiotherapy15%
4 Other Subdomains22%

Selected Abstracts

Current Awareness in Hematological Oncology

HEMATOLOGICAL ONCOLOGY, Issue 2 2008
Article first published online: 28 MAY 200
In order to keep subscribers up-to-date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of hematological oncology. Each bibliography is divided into 14 sections: 1 Reviews; 2 General; Leukemias: 3 Lymphoblastic; 4 Myeloid & Myelodysplastic Syndromes; 5 Chronic; 6 Others; Lymphomas: 7 Hodgkin's; 8 Non-Hodgkin's; 9 Plasmacytomas/Multiple Myelomas; 10 Others; 11 Bone Marrow Transplantation; 12 Cytokines; 13 Diagnosis; 14 Cytogenetics. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted. [source]

Current Awareness in Hematological Oncology

HEMATOLOGICAL ONCOLOGY, Issue 4 2003
Article first published online: 15 JAN 200
In order to keep subscribers up-to-date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of hematological oncology. Each bibliography is divided into 14 sections: 1 Books, Reviews & Symposia; 2 General; Leukemias: 3 Lymphoblastic; 4 Myeloid & Myelodysplastic Syndromes; 5 Chronic; 6 Others; Lymphomas: 7 Hodgkin's; 8 Non-Hodgkin's; 9 Plasmacytomas/Multiple Myelomas; 10 Others; 11 Bone Marrow Transplantation; 12 Cytokines; 13 Diagnosis; 14 Cytogenetics. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted. [source]

Current Awareness in Hematological Oncology

HEMATOLOGICAL ONCOLOGY, Issue 4 2002
Article first published online: 5 DEC 200
In order to keep subscribers up-to-date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of hematological oncology. Each bibliography is divided into 14 sections: 1 Books, Reviews & Symposia; 2 General; Leukemias: 3 Lymphoblastic; 4 Myeloid & Myelodysplastic Syndromes; 5 Chronic; 6 Others; Lymphomas: 7 Hodgkin's; 8 Non-Hodgkin's; 9 Plasmacytomas/Multiple Myelomas; 10 Others; 11 Bone Marrow Transplantation; 12 Cytokines; 13 Diagnosis; 14 Cytogenetics. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted. [source]

Current Awareness in Hematological Oncology

HEMATOLOGICAL ONCOLOGY, Issue 3 2002
Article first published online: 29 AUG 200
In order to keep subscribers up-to-date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of hematological oncology. Each bibliography is divided into 14 sections: 1 Books, Reviews & Symposia; 2 General; Leukemias: 3 Lymphoblastic; 4 Myeloid & Myelodysplastic Syndromes; 5 Chronic; 6 Others; Lymphomas: 7 Hodgkin's; 8 Non-Hodgkin's; 9 Plasmacytomas/Multiple Myelomas; 10 Others; 11 Bone Marrow Transplantation; 12 Cytokines; 13 Diagnosis; 14 Cytogenetics. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted. [source]

Current Awareness in Hematological Oncology

HEMATOLOGICAL ONCOLOGY, Issue 4 2001
Article first published online: 17 DEC 200
In order to keep subscribers up-to-date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of hematological oncology. Each bibliography is divided into 14 sections: 1 Books, Reviews & Symposia; 2 General; Leukemias: 3 Lymphoblastic; 4 Myeloid & Myelodysplastic Syndromes; 5 Chronic; 6 Others; Lymphomas: 7 Hodgkin's; 8 Non-Hodgkin's; 9 Plasmacytomas/Multiple Myelomas; 10 Others; 11 Bone Marrow Transplantation; 12 Cytokines; 13 Diagnosis; 14 Cytogenetics. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted. [source]

Quality of life and use of red cell transfusion in patients with myelodysplastic syndromes.

AMERICAN JOURNAL OF HEMATOLOGY, Issue 10 2009
A systematic review
The main treatment for many patients with Myelodysplastic Syndromes (MDS) remains red cell transfusion to attenuate the symptoms of chronic anemia. Fatigue can reduce a patient's health related quality of life (HRQoL), but there is little understanding of the optimal use of transfusions to improve this. A systematic review was performed to identify and appraise publications reporting the use of HRQoL instruments in patients with MDS. A total of 17 separate studies were identified that used 14 HRQoL instruments, but only one MDS disease specific HRQoL instrument (QOL-E) was reported. Two well established HRQoL instruments were most often used in MDS research (variants of the Functional Assessment of Cancer Therapy (FACT) and the European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (QLQ-C30)). Several common problems were identified in the published literature including a lack of power calculations to detect clinically relevant changes, small sample sizes and significant attrition rates for completion of HRQoL assessments, all of which limit the strength of any conclusions. There is no consensus on the optimal transfusion regimen to improve HRQoL in transfusion-dependent MDS. Future research into HRQoL within MDS is a pressing requirement. Studies should focus on the domains that are of most clinical importance to the patient as well as traditional quantitative changes of hemoglobin concentration. Am. J. Hematol., 2009. © 2009 Wiley-Liss, Inc. [source]

Consensus statement on iron overload in myelodysplastic syndromes,

AMERICAN JOURNAL OF HEMATOLOGY, Issue 11 2008
John M. Bennett
In May 2005 at the 8th International Symposium on Myelodysplastic Syndromes (MDS), a consensus meeting was held on iron overload in MDS (Seymour, Hematol Oncol Clin 2005; Suppl 1:18,25). The recommendations of the 2005 consensus meeting were discussed in the context of currently available evidence at the 9th International Symposium on Myelodysplastic Syndromes in Florence Italy, May 2007. The recommendations of the consensus working group are presented here. The recommendations are a continued refinement of the outcome of the 2005 consensus meeting and the ground-breaking work of others in this area (Seymour, Hematol Oncol Clin 2005; Suppl 1:18,25; Gattermann, Int J Hematol 2008;88:24,29; Alessandrino et al., Haematologica 2002;87:1286,1306; NCCN practice guidelines: Myelodysplastic Syndromes, version 2.2008). Am. J. Hematol., 2008. © 2008 Wiley-Liss, Inc. [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]

Peripheral blood MDS score: A new flow cytometric tool for the diagnosis of myelodysplastic syndromes,

CYTOMETRY, Issue 1 2005
Sindhu Cherian
Abstract Background Myelodysplastic syndromes (MDS) are a heterogeneous group of hematopoietic disorders diagnosed using morphologic and clinical findings supported by cytogenetics. Because abnormalities may be subtle, diagnosis using these approaches can be challenging. Flow cytometric (FCM) approaches have been described; however the value of bone marrow immunophenotyping in MDS remains unclear due to the variability in detected abnormalities. We sought to refine the FCM approach by using peripheral blood (PB) to create a clinically useful tool for the diagnosis of MDS. Methods PB from 15 patients with MDS was analyzed by multiparametric flow cytometry using an extensive panel of monoclonal antibodies. Patterns of neutrophil antigen expression were compared with those of normal controls (n = 16) to establish light scatter and/or immunophenotypic abnormalities that correlated with MDS. A scoring algorithm was developed and validated prospectively on a blinded patient set. Results PB neutrophils from patients with MDS had lower side scatter and higher expression of CD66 and CD11a than did controls. Some MDS PB neutrophils demonstrated abnormal CD116 and CD10 expression. Because none of these abnormalities proved consistently diagnostic, we sought to increase the power of the assay by devising a scoring system to allow the association of multiple abnormalities and account for phenotypic variations. The PB MDS score differentiated patients with MDS from controls (P < 0.0001) in the test set. In a prospective validation, the PB MDS score successfully identified patients with MDS (sensitivity 73%, specificity 90%). Conclusions FCM analysis of side scatter and only four additional immunophenotypic parameters of PB neutrophils using the PB MDS score proved more sensitive than standard laboratory approaches and may provide an additional, more reliable diagnostic tool in the identification of MDS. © 2005 Wiley-Liss, Inc. [source]

Absence of p16 and p27 gene rearrangements and mutations in de novo myelodysplastic syndromes

EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2005
Sotirios G. Papageorgiou
Abstract:, Myelodysplastic syndromes (MDS) represent a group of clonal hematopoietic disorders characterized by dyshemopoiesis and frequent evolution to acute leukemia. Tumor suppressor gene inactivation may be involved in MDS pathogenesis. The two families of cyclin-dependent kinase inhibitors (CDKIs) (INK4 family of p15, p16, p18 and p19 and CIP/KIP family of p21, p27 and p57) that negatively regulate cell cycle progression are known tumor suppressor genes. To determine whether genetic alterations of p16 and p27 genes play an important role in MDS pathogenesis, we examined DNA from 51 patients classified as 17 refractory anemias (RA), four refractory anemias with ringed sideroblasts (RARS), 19 refractory anemias with an excess of blasts (RAEB), 5 refractory anemias with excess of blasts in transformation (RAEB-t) and 6 chronic myelomonocytic leukemias (CMML). Southern blot analysis detected no homozygous deletions of p16 and p27. Polymerase chain reaction,single-strand conformation polymorphism (PCR,SSCP) and sequencing did not reveal point mutations for both genes with the exception of two allelic polymorphisms, namely a C , G transition at 447 bp of p16exon3 and a T , A transition at 791 bp of p27exon1 genes. Our results suggest that mutations of p16 and p27 genes resulting in abnormal p16 and p27 proteins do not represent a mechanism of gene inactivation involved in the pathogenesis of MDS. [source]

Incidence of myelodysplastic syndromes within a nonprofit healthcare system in western Washington state, 2005,2006,

AMERICAN JOURNAL OF HEMATOLOGY, Issue 10 2010
Anneclaire J. De Roos
Myelodysplastic syndromes (MDS) incidence is unclear because of historical lack of population-based registration and possibly because of underdiagnosis. We conducted a study to evaluate completeness of MDS registration in the Seattle-Puget Sound region of the Surveillance, Epidemiology, and End Results (SEER) program,which has reported the highest rates among the SEER registries since mandatory reporting of MDS began in 2001. We identified incident MDS cases of any age that occurred within a nonprofit healthcare system in western Washington State in 2005 or 2006 through the local SEER registry or by relevant diagnostic code followed by medical chart review to classify these patients as unlikely, possible, or definite/probable MDS. We calculated age-standardized incidence rates for all identified MDS cases and for case groups based on identification method, and we summarized medical histories of the MDS patients. MDS incidence in our study population was estimated as 7.0 per 100,000 person-years in 2005,2006 when combining MDS cases identified by SEER and definite/probable cases identified by chart review, which was similar to the rate of 6.9 reported by our local SEER registry. The addition of possible MDS cases identified from chart review increased the rate to 10.2 per 100,000. MDS patients frequently had previous cancer diagnoses (25%) and comorbidities such as high blood pressure and diabetes. Our investigation suggests that although reporting of confirmed MDS diagnoses in our region appears complete, MDS incidence is likely underestimated because of omission of cases who are symptomatic but do not receive definitive diagnoses. Am. J. Hematol., 2010. © 2010 Wiley-Liss, Inc. [source]

Myelodysplastic syndromes associated with interstitial deletion of chromosome 5q: Clinicopathologic correlations and new insights from the prelenalidomide era,,

AMERICAN JOURNAL OF HEMATOLOGY, Issue 9 2008
Shernan G. Holtan
To better estimate prognosis for patients with myelodysplastic syndromes (MDS) associated with clonal interstitial deletions of the long arm of chromosome 5 (del(5q)), we reviewed the medical records of 130 adults with del(5q) MDS seen at our institution over a 15-year period. Overall median survival of this cohort was 9.5 months, shorter than reported in earlier series. The least favorable outcomes are associated with complex cytogenetics, lack of any normal metaphases, normocytic rather than macrocytic erythrocyte indices, and low baseline lymphocyte counts. Lymphopenia but not neutropenia at the time of diagnosis appears to be a new adverse prognostic indicator. Cytogenetic breakpoints defined by G-banded karyotyping correlate poorly with particular disease features. Surprisingly, survival of patients with treatment-related MDS was equivalent to that of de novo MDS with del(5q) in this series. Morphologic features associated with del(5q) are diverse. Most patients with del(5q) MDS do not meet criteria for WHO-defined 5q-syndrome, and the presence of del(5q) does not appear to modify the clinical phenotype otherwise risk-stratified by the International Prognostic Scoring System (IPSS). Additional important prognostic factors not taken into account by the IPSS include the baseline erythrocyte indices, lymphocyte count, and clonal burden. Am. J. Hematol., 2008. © 2008 Wiley-Liss, Inc. [source]

Bone marrow cells from myelodysplastic syndromes show altered immunophenotypic profiles that may contribute to the diagnosis and prognostic stratification of the disease: A pilot study on a series of 56 patients,

CYTOMETRY, Issue 3 2010
Sergio Matarraz
Abstract A heterogeneous spectrum of immunophenotypic abnormalities have been reported in myelodysplastic syndromes (MDS). However, most studies are restricted to the analysis of CD34+ cells and/or other major subsets of CD34, cells, frequently not exploring the diagnostic and prognostic impact of immunophenotyping. Methods: We propose for the first time an immunophenotypic score (IS) based on the altered distribution and immunophenotypic features of maturing/mature compartments of bone marrow (BM) hematopoietic cells in 56 patients with MDS that could contribute to a refined diagnosis and prognostic evaluation of the disease. Results: Although MDS-associated phenotypes were detected in reactive BM, the overall immunophenotypic profile of BM cells allowed an efficient discrimination between MDS and both normal and reactive BM, once the number and degree of severity of the abnormalities detected per patient were simultaneously considered in the proposed IS. Interestingly, increasingly higher IS were found among patients with MDS showing adverse prognostic factors and in low- versus high-grade cases. The most informative prognostic factors included the number of CD34+ cells, presence of aberrant CD34,/CD117+ precursors, decreased mature neutrophils and CD34, erythroid precursors, and increased numbers of CD36,/lo erythroid precursors; in addition, the IS was an independent prognostic factor for overall survival. Conclusions: Assessment of immunophenotypic abnormalities of maturing/mature BM cells allows an efficient discrimination between MDS and both normal and reactive BM, once the number and degree of severity of the abnormalities detected are simultaneously scored. Interestingly, progressively higher IS were found among patients with MDS with adverse prognostic features and shorter overall survival. © 2010 Clinical Cytometry Society [source]

Peripheral blood MDS score: A new flow cytometric tool for the diagnosis of myelodysplastic syndromes,

CYTOMETRY, Issue 1 2005
Sindhu Cherian
Abstract Background Myelodysplastic syndromes (MDS) are a heterogeneous group of hematopoietic disorders diagnosed using morphologic and clinical findings supported by cytogenetics. Because abnormalities may be subtle, diagnosis using these approaches can be challenging. Flow cytometric (FCM) approaches have been described; however the value of bone marrow immunophenotyping in MDS remains unclear due to the variability in detected abnormalities. We sought to refine the FCM approach by using peripheral blood (PB) to create a clinically useful tool for the diagnosis of MDS. Methods PB from 15 patients with MDS was analyzed by multiparametric flow cytometry using an extensive panel of monoclonal antibodies. Patterns of neutrophil antigen expression were compared with those of normal controls (n = 16) to establish light scatter and/or immunophenotypic abnormalities that correlated with MDS. A scoring algorithm was developed and validated prospectively on a blinded patient set. Results PB neutrophils from patients with MDS had lower side scatter and higher expression of CD66 and CD11a than did controls. Some MDS PB neutrophils demonstrated abnormal CD116 and CD10 expression. Because none of these abnormalities proved consistently diagnostic, we sought to increase the power of the assay by devising a scoring system to allow the association of multiple abnormalities and account for phenotypic variations. The PB MDS score differentiated patients with MDS from controls (P < 0.0001) in the test set. In a prospective validation, the PB MDS score successfully identified patients with MDS (sensitivity 73%, specificity 90%). Conclusions FCM analysis of side scatter and only four additional immunophenotypic parameters of PB neutrophils using the PB MDS score proved more sensitive than standard laboratory approaches and may provide an additional, more reliable diagnostic tool in the identification of MDS. © 2005 Wiley-Liss, Inc. [source]

CD87 as a marker for terminal granulocytic maturation: Assessment of its expression during granulopoiesis

CYTOMETRY, Issue 1 2003
M. Tarek Elghetany
Abstract Background Understanding the normal surface maturation pattern of granulocytes is essential for the recognition of abnormal patterns, which in turn may be of diagnostic or pathogenetic significance in disorders such as myelodysplastic syndromes and inherited bone marrow failure disorders. CD87 plays a role in cellular interaction, cell migration, and inflammatory response. Surface expression of this antigen has not been adequately studied on bone marrow granulocytes, and the small number of previous studies has provided conflicting data. Methods Bone marrow aspirates from 11 control subjects were studied by flow cytometry and a lysed whole blood technique to compare surface expression of CD87 on marrow granulocytes with those of CD11b, CD16, CD35, and CD10, which are expressed at the myelocyte, metamyelocyte, band, and segmented stage of neutrophilic development, respectively. Four sorting experiments of CD87+ granulocytes were also performed. Results Our study showed no statistical difference between surface expression of CD35 and CD87 (P > 0.3), whereas significant differences existed between CD87 and the other antibodies (P < 0.004). Sorting experiments showed that more than 80% of CD87+ cells were bands and segmented neutrophils. Dual staining for CD87 and CD35 showed that most CD87+ granulocytes coexpress CD35. Conclusions CD87 is expressed on granulocytes at the band and segmented neutrophil stage of development and can be used to study normal and abnormal granulopoiesis. Cytometry Part B (Clin. Cytometry) 51B:9,13, 2003. © 2002 Wiley-Liss, Inc. [source]

Elevated tryptase levels selectively cluster in myeloid neoplasms: a novel diagnostic approach and screen marker in clinical haematology

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 10 2009
W. R. Sperr
Abstract Background, Recent data suggest that tryptase, a mast cell enzyme, is expressed in neoplastic cells in myeloid leukaemias. In several of these patients, increased serum tryptase levels are detectable. Materials and methods, We have determined serum tryptase levels in 914 patients with haematological malignancies, including myeloproliferative disorders (n = 156), myelodysplastic syndromes (MDS, n = 241), acute myeloid leukaemia (AML, n = 317), systemic mastocytosis (SM, n = 81), non-Hodgkin,s lymphoma (n = 59) and acute lymphoblastic leukaemia (n = 26). Moreover, tryptase was measured in 136 patients with non-neoplastic haematological disorders, 102 with non-haematological disorders and 164 healthy subjects. Results, In healthy subjects, the median serum tryptase was 5·2 ng mL,1. Elevated serum tryptase levels were found to cluster in myeloid neoplasm, whereas almost all patients with lymphoid neoplasms exhibited normal tryptase. Among myeloid neoplasms, elevated tryptase levels (> 15 ng mL,1) were recorded in > 90% of patients with SM, 38% with AML, 34% with CML and 25% with MDS. The highest tryptase levels, often > 1000 ng mL,1, were found in advanced SM and core-binding-factor leukaemias. In most patients with non-neoplastic haematological disorders and non-haematological disorders analysed in our study, tryptase levels were normal, the exception being a few patients with end-stage kidney disease and helminth infections, in whom a slightly elevated tryptase was found. Conclusions, In summary, tryptase is a new diagnostic marker of myeloid neoplasms and a useful test in clinical haematology. [source]

Minimal diagnostic criteria for myelodysplastic syndromes and separation from ICUS and IDUS: update and open questions

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 7 2009
P. Valent
Abstract Although a classification for myelodysplastic syndromes (MDS) has been proposed by several working groups and by the World Health Organization (WHO), with criteria useful to discriminate between disease variants, the important issue of minimal diagnostic criteria of MDS has only recently been addressed. In the current article, proposed minimal diagnostic criteria for MDS are discussed together with two conditions that do not meet these criteria, although cytopenia or dysplasia is present. These two conditions, idiopathic cytopenia of unknown significance and idiopathic dysplasia of unknown significance should be kept in mind as a provisional (potential) diagnosis in patients with suspected MDS. Both conditions can progress to frank MDS over time. Therefore, once diagnosed, these patients should have a haematological follow-up. The diagnosis MDS, on the other hand, needs to be based on robust criteria and exclusion of all other causes of cytopenia and dysplasia, which requires detailed and sometimes extensive investigations, including a bone marrow biopsy, cytogenetic analyses, molecular studies and flow cytometry. [source]

Mixed-lineage eosinophil/basophil crisis in MDS: a rare form of progression

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 6 2008
F. Wimazal
ABSTRACT Background, Basophilic crisis and eosinophilia are well recognized features of advanced chronic myeloid leukaemia. In other myeloid neoplasms, however, transformation with marked basophilia and eosinophilia is considered unusual. Design, We examined the long-term follow-up of 322 patients with de novo myelodysplastic syndromes (MDS) to define the frequency of basophilic, eosinophilic and mixed lineage (basophilic and eosinophilic) transformation. Results, Of all patients, only one developed mixed lineage crisis (, 20% basophils and , 20% eosinophils). In this patient, who initially suffered from chronic myelomonocytic leukaemia, basophils increased to 48% and eosinophils up to 31% at the time of progression. Mixed lineage crisis was not accompanied by an increase in blast cells or organomegaly. The presence of BCR/ABL and other relevant fusion gene products (FIP1L1/PDGFRA, AML1/ETO, PML/RAR,, CBF,/MYH11) were excluded by PCR. Myelomastocytic transformation/myelomastocytic leukaemia and primary mast cell disease were excluded by histology, KIT mutation analysis, electron microscopy and immunophenotyping. Basophils were thus found to be CD123+, CD203c+, BB1+, KIT- cells, and to express a functional IgE-receptor. Among the other patients with MDS examined, 4(1·2%) were found to have marked basophilia (, 20%) and 7(2·1%) were found to have massive eosinophilia ( , 20%), whereas mixed-lineage crisis was detected in none of them. Conclusions, Mixed basophil/eosinophil crisis may develop in patients with MDS but is an extremely rare event. [source]

Quantitative, phenotypic, and functional evaluation of basophils in myelodysplastic syndromes

EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 10 2001
W. Füreder
Background The myelodysplastic syndromes (MDS) are a group of clonal haematological disorders characterized by cytopenia(s), reduced differentiation-capacity of myeloid cells, and impaired leukocyte function. However, little is known so far about basophil granulocytes in MDS. Design We have compared the numbers, phenotype and function of basophils in MDS patients with those in healthy subjects. A total numer of 23 patients with MDS (refractory anaemia, n = 8; refractory anaemia with ringsideroblasts, n = 7; refractory anaemia with excess of blasts/refractory anaemia with excess of blasts in transformation, n = 8) and 20 healthy donors were included. Results The numbers of blood basophils in MDS patients (34·6 ± 62·9 ,L,1) was lower compared to healthy controls (58·6 ± 64·9 ,L,1). Correspondingly, whole blood histamine levels were lower in MDS patients (MDS 34·1 ± 29·1 ng mL,1 vs. normal donors 72·0 ± 36·9 ng mL,1). Like ,normal' basophils, basophils in MDS expressed interleukin-3 receptor , (CD123), E-NPP3 (CD203c), CR1 (CD35), CR3 (CD11b), CR4 (CD11c), membrane co-factor protein (CD46), decay-accelerating factor (CD55) and membrane attack complex inhibitory factor (CD59), as well as receptors for C3a, C5a (CD88), and IgE. Recombinant human (rh) C5a and anti-IgE induced significant release of histamine from basophils in both groups of donors without significant differences between MDS and healthy controls. Conclusions The absolute numbers of basophils in MDS patients are lower than in normal donors. However, basophils in MDS do not differ from their ,normal counterparts' in terms of complement receptor expression, IgE-receptor expression, or functional responses to respective ligands. [source]

Epigenetic therapy in myelodysplastic syndromes

EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2010
Caterina Musolino
Abstract The wide spectrum of clonal hematopoietic disorders that fall under the broad diagnostic category of myelodysplastic syndromes (MDS) consist of a family of bone marrow malignancies , with ineffective, inadequate, and dysplastic hematopoiesis, and with an increased risk of life-threatening infections, bleeding, and progression to acute myeloid leukemia (AML) , that are characterized by a deep heterogeneity on the clinical, biologic and prognostic level. The intrinsic complexity of this group of disorders and the frequent association with one or more comorbidities have limited for many years the number of effective treatment options available: most patients are, indeed, still managed by supportive care measures, with just a minority of them being eligible for allogeneic stem cell transplantation, which is still the only potentially curative modality. In the last two decades, the progressively better understanding of MDS biology has shown how an abnormal epigenetic modulation might play a crucial part in the pathogenesis and in the process of biologic evolution of these disorders. Moreover, pharmacological agents that target the so-called epigenome have shown a significant clinical activity for diverse hematologic malignancies, including MDS. The aim of this review is to highlight recent developments within the context of current knowledge of MDS and its altered epigenetic regulation and to recall the experimental steps that have brought to the clinical development and application of epigenetic modifiers, such as azacytidine and decitabine, trying to explain the biologic rationale for their use in this setting. [source]

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

EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2010
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]

Redefining monosomy 5 by molecular cytogenetics in 23 patients with MDS/AML

EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2007
Angèle Herry
Abstract Deletion of the long arm of chromosome 5 [del(5q)] or loss of a whole chromosome 5 (,5) is a common finding, arising de novo in 10% of patients with myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) and in 40% of patients with therapy-related MDS or AML. We investigated by molecular cytogenetics 23 MDS/AML patients for whom conventional cytogenetics detected a monosomy 5. Monosomy 5 was redefined as unbalanced or balanced translocation and ring of chromosome 5. Loss of 5q material was identified in all 23 patients, but one. One copy of EGR1(5q31) or CSF1R(5q33,34) genes was lost in 22 of the 23 patients. Chromosome 5p material was a constant chromosomal component of derivative chromosomes or rings in all patients, but one. Sequential fluorescent in situ hybridization studies with whole chromosome paints and region-specific probes, used as a complement to conventional cytogenetic analysis, allow a better interpretation of karyotypes in MDS/AML patients. [source]

Absence of p16 and p27 gene rearrangements and mutations in de novo myelodysplastic syndromes

EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2005
Sotirios G. Papageorgiou
Abstract:, Myelodysplastic syndromes (MDS) represent a group of clonal hematopoietic disorders characterized by dyshemopoiesis and frequent evolution to acute leukemia. Tumor suppressor gene inactivation may be involved in MDS pathogenesis. The two families of cyclin-dependent kinase inhibitors (CDKIs) (INK4 family of p15, p16, p18 and p19 and CIP/KIP family of p21, p27 and p57) that negatively regulate cell cycle progression are known tumor suppressor genes. To determine whether genetic alterations of p16 and p27 genes play an important role in MDS pathogenesis, we examined DNA from 51 patients classified as 17 refractory anemias (RA), four refractory anemias with ringed sideroblasts (RARS), 19 refractory anemias with an excess of blasts (RAEB), 5 refractory anemias with excess of blasts in transformation (RAEB-t) and 6 chronic myelomonocytic leukemias (CMML). Southern blot analysis detected no homozygous deletions of p16 and p27. Polymerase chain reaction,single-strand conformation polymorphism (PCR,SSCP) and sequencing did not reveal point mutations for both genes with the exception of two allelic polymorphisms, namely a C , G transition at 447 bp of p16exon3 and a T , A transition at 791 bp of p27exon1 genes. Our results suggest that mutations of p16 and p27 genes resulting in abnormal p16 and p27 proteins do not represent a mechanism of gene inactivation involved in the pathogenesis of MDS. [source]

Apoptotic rate varies with detection methods in myelodysplastic syndromes: impact of method selection

EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2002
Jong Weon Choi
No abstract is available for this article. [source]

Focal 9p instability in hematologic neoplasias revealed by comparative genomic hybridization and single-nucleotide polymorphism microarray analyses

GENES, CHROMOSOMES AND CANCER, Issue 4 2010
Anu Usvasalo
Copy number losses in chromosome arm 9p are well-known aberrations in malignancies, including leukemias. The CDKN2A gene is suggested to play a key role in these aberrations. In this study overviewing 9p losses in hematologic neoplasias, we introduce the term focal 9p instability to indicate multiple areas of copy number loss or homozygous loss within a larger heterozygous one in 9p. We have used microarray comparative genomic hybridization to study patients with acute lymphoblastic leukemia (ALL, n = 140), acute myeloid leukemia (n = 50), chronic lymphocytic leukemia (n = 20), and myelodysplastic syndromes (n = 37). Our results show that 9p instability is restricted to ALL. In total, 58/140 (41%) patients with ALL had a loss in 9p. The 9p instability was detected in 19% of the patients with ALL and always included homozygous loss of CDKN2A along with loss of CDKN2B. Other possibly important genes included MTAP, IFN, MLLT3, JAK2, PTPLAD2, and PAX5. 13/27 (48%) patients with the instability had the BCR/ABL1 fusion gene or other oncogene-activating translocation or structural aberrations. Two patients had homozygous loss of hsa-mir ,31, a microRNA known to regulate IKZF1. IKZF1 deletion at 7p12.1 was seen in 10 (37%) patients with the 9p instability. These findings suggest that, in ALL leukemogenesis, loss of CDKN2A and other target genes in the instability region is frequently associated with BCR/ABL1 and IKZF1 dysfunction. The multiple mechanisms leading to 9p instability including physical or epigenetic loss of the target genes, loss of the microRNA cluster, and the role of FRA9G fragile site are discussed. © 2009 Wiley-Liss, Inc. [source]

Expression of NUP98/TOP1, but not of TOP1/NUP98, in a treatment-related myelodysplastic syndrome with t(10;20;11)(q24;q11;p15)

GENES, CHROMOSOMES AND CANCER, Issue 2 2002
Ioannis Panagopoulos
The t(11;20)(p15;q11) is a rare but recurrent translocation that so far has been described in only four acute myeloid leukemias (AMLs), two treatment-related myelodysplastic syndromes (t-MDSs), and one case of polycythemia vera. Recently, the t(11;20) was shown to result in a fusion of the NUP98 and TOP1 genes, with expression of the NUP98/TOP1 chimera encoded by the der(11)t(11;20), but not of the reciprocal TOP1/NUP98 on the der(20)t(11;20). The genomic breakpoints were subsequently mapped to introns 13 and 7 of NUP98 and TOP1, respectively. We present here a t-MDS with a three-way variant translocation, t(10;20;11)(q24;q11;p15), that generates a der(11)t(11;20) but not a der(20)t(11;20), strongly suggesting that the der(11) harbors the critical genetic rearrangement. Reverse transcriptase,polymerase chain reaction (RT-PCR) revealed a NUP98/TOP1 fusion in which exon 13 of NUP98 was fused in-frame with exon 8 of TOP1. Extra long (XL) genomic PCR and subsequent sequence analyses showed that the breakpoint in NUP98 occurred at nucleotide (nt) 3461 of intron 13, close to a MER (medium reiteration frequency interspersed repetitive element) repeat, and that the breakpoint in TOP1 was at nt 1436 of intron 7, downstream of a MIR (mammalian-wide interspersed repeats) repetitive element. Genomic XL PCR did not amplify the reciprocal TOP1/NUP98, nor was this chimera expressed, as expected from the cytogenetic finding. The present results provide further support for the involvement of the NUP98/TOP1 transcript, but not of the reciprocal one, in the development of MDS/AML. Furthermore, the three cases genomically characterized to date have all been treatment-related and have all harbored breakpoints in intron 13 of NUP98 and intron 7 of TOP1, suggesting that these introns are susceptible to chemotherapy-induced breakage. © 2002 Wiley-Liss, Inc. [source]

International workshop on the relationship of prior therapy to balanced chromosome aberrations in therapy-related myelodysplastic syndromes and acute leukemia: Overview report

GENES, CHROMOSOMES AND CANCER, Issue 4 2002
Janet D. Rowley
First page of article [source]

Data management and statistical methods used in the analysis of balanced chromosome abnormalities in therapy-related myelodysplastic syndromes and therapy-related acute leukemia: Report from an International Workshop,

GENES, CHROMOSOMES AND CANCER, Issue 4 2002
Theodore Karrison
First page of article [source]

Arsenic derivatives in hematologic malignancies: a role beyond acute promyelocytic leukemia?

HEMATOLOGICAL ONCOLOGY, Issue 4 2006
Srdan Verstovsek
Abstract The importance of arsenic trioxide (As2O3) has been underscored over the last decade due to its efficacy against acute promyelocytic leukemia (APL), a disease in which this agent has been associated with complete hematologic and molecular remission rates of 87% and 83%, respectively. The different molecular mechanisms of action of As2O3 suggest its applicability in hematologic malignancies other than APL. However, responses obtained thus far have consisted of improvements in signs and symptoms without the elimination of a given disease. Toxicities derived from As2O3 are significant but manageable and reversible. However, the risk/benefit ratio of As2O3 in hematologic malignancies other than APL is still unclear. The development of new generations of orally bioavailable inorganic, as well as new organic, arsenic compounds with improved toxicity profiles may bolster the therapeutic application of arsenic derivatives in hematologic malignancies such as leukemia, multiple myeloma and myelodysplastic syndromes. Copyright © 2006 John Wiley & Sons, Ltd. [source]

The utility of the Sysmex XE-2100 analyzer's NEUT-X and NEUT-Y parameters for detecting neutrophil dysplasia in myelodysplastic syndromes

INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 3 2010
J. R. FURUNDARENA
Summary The diagnosis of myelodysplastic syndromes (MDS) is based on morphological changes in the blood and bone marrow. The parameters NEUT-X and NEUT-Y of the Sysmex XE-2100 analyzer could help detect neutrophil dysplasia. A control group of 50 patients, along with 50 postpartum patients, 50 anemias, 50 leukopenias, 50 patients with microscopically visible hypergranulated neutrophils and 50 MDS patients were assessed. The NEUT-X and NEUT-Y values (mean ± SD) for the control group were 1346 ± 28.2 and 420 ± 19.3, respectively, with the anemia and leukopenia groups giving similar values. The postpartum and hypergranulated neutrophils groups presented higher values (P < 0.05), whereas the values in the MDS group were 1286 ± 72.8 and 385 ± 50.9 (P < 0.05), respectively. There were no differences between the morphological MDS types. The NEUT-X and NEUT-Y values in MDS patients with optical hypogranulation were significantly lower than for MDS patients without optical hypogranulation. NEUT-X and NEUT-Y values lower than 1298 and 398, respectively, would have a specificity for detecting MDS of 94% and 91% and would detect 60% and 56% of cases, respectively, whereas they would detect 75% and 74%, respectively, of MDS cases with optical hypogranulation. NEUT-X and NEUT-Y parameters can be used to detect neutrophil dysplasia arising from MDS and chronic myelomonocytic leukemia. [source]