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Myelogenous Leukemia (myelogenous + leukemia)
Kinds of Myelogenous Leukemia Selected AbstractsAn 85-Year-Old Japanese Woman with Philadelphia Chromosome,Positive Chronic Myelogenous Leukemia with Del (5q) Successfully Treated by Intermittent Imatinib TherapyJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 10 2004Toyoki Maeda MD No abstract is available for this article. [source] Reciprocal Relationship Between a Ph-Negative Clone With Trisomy 8 Associated With Severe Myelodysplasia and a Ph-Positive Clone Following Imatinib Treatment in a Patient With Accelerated-Phase Chronic Myelogenous Leukemia (CML)AMERICAN JOURNAL OF HEMATOLOGY, Issue 4 2004Paulina Patchenko No abstract is available for this article. [source] Optimization of a flow cytometry-based protocol for detection and phenotypic characterization of multipotent mesenchymal stromal cells from human bone marrowCYTOMETRY, Issue 6 2006Elena A. Jones Abstract Background: To study the biology of rare bone marrow (BM) multipotent mesenchymal stromal cells (MSCs), recognized protocols are needed. Colony-forming unit-fibroblast (CFU-F) assays have historically been used for the enumeration of MSCs. However, the need to isolate and further analyze MSCs requires new strategies based on cell surface markers. The purpose of this work was to verify the phenotype of BM MSCs in vivo and to develop flow cytometry-based methods for their evaluation. Methods: Pre-enrichment with D7-FIB-conjugated microbeads, cell sorting for CD45lowD7-FIB+LNGFR+ cells, and CFU-F assay were used to confirm the phenotype of BM MSCs in vivo. Further phenotypic characterization of MSCs was performed using three-color flow cytometry following pre-enrichment or by direct four-color flow cytometry. The sensitivity of direct flow cytometry/rare event analysis for the accurate enumeration of MSCs was validated using 85 samples from patients with neoplastic BM diseases. Results: In normal BM, a significant correlation was found between the frequencies of CFU-Fs and CD45lowD7-FIB+LNGFR+ cells (n = 19, R = 0.719, P = 0.001). Following cell sorting, ,15% of these cells were clonogenic. The same cells were enriched using LNGFR-based positive selection, CD45/Glycophorin A-based depletion, or plastic adherence. CD45lowD7-FIB+LNGFR+ cells expressed classic makers of cultured MSCs CD73/SH3 and CD105/SH2 and markers of stromal reticular cells CD106/VCAM and alkaline phosphatase. Novel markers were identified including leukemia inhibitory factor receptor and gp130. CD45lowD7-FIB+LNGFR+ cells were increased fourfold in the floating fat fraction of normal BM aspirates. Their frequency was decreased in chronic lymphocytic leukemia (threefold, n = 13, P = 0.049) and chronic myelogenous leukemia (ninefold, n = 11, P = 0.001) compared with that in age-matched controls (n = 26 and n = 31, respectively). Conclusions: This study demonstrates the usefulness of flow cytometry-based methods for the detection, enumeration and further phenotypic analysis of BM MSCs. These findings have broad applications for the future evaluation of BM MSCs in health and disease. © 2006 International Society for Analytical Cytology [source] Esophageal aspergillosis in cytologic brushings: Report of two cases associated with acute myelogenous leukemiaDIAGNOSTIC CYTOPATHOLOGY, Issue 5 2004Simon Bergman M.D. Abstract Aspergillus, which commonly involves the sinonasal region and upper respiratory tract, is reported for the first time in esophageal brushings in two immunocompromised patients with a history of acute myelogenous leukemia (AML). Aspergillus species was identified in both cases in smears as scattered three-dimensional groups of fungi with 45° angle branching. One case had a local esophageal noninvasive form, while the other, in addition to the esophagus, had disseminated to the spleen. Although Aspergillus is an uncommon cause of esophagitis in immunocompromised patients, its presence may be associated with an extremely poor prognosis as both expired shortly after detecting this fungus on esophageal brushings. Diagn. Cytopathol. 2004;30:347,349. © 2004 Wiley-Liss, Inc. [source] Novel agents to override imatinib resistance mechanismsDRUG DEVELOPMENT RESEARCH, Issue 7 2008Asumi Yokota Abstract Chronic myelogenous leukemia (CML) is a disorder of hematopoietic stem cells that results from the Philadelphia chromosome (Ph) created through translocation of human chromosomes 9 and 22. The resulting Bcr-Abl fusion protein has constitutively high tyrosine kinase activity that causes transformation of hematopoietic stem cells. Imatinib mesylate (IM) was developed as a specific Bcr-Abl kinase inhibitor and is efficacious in treating Ph-chromosome-positive (Ph+) leukemias such as CML and Ph+ acute lymphoblastic leukemia (ALL). Within a few years of its introduction to the clinic, IM has dramatically altered the first-line therapy for CML. Although most newly diagnosed CML patients in the chronic phase (CP) achieved durable responses when treated with IM, resistance to IM has become a major problem in patients with advanced-stage disease. The most important mechanism of IM resistance are point mutations within the Abl kinase domain; therefore, there is an urgent need for novel agents that can inhibit mutated Bcr-Abl. In this review, we describe novel Bcr-Abl tyrosine kinase inhibitors, the so-called "Super Gleevec" inhibitors. Drug Dev Res 69:398,406, 2008. © 2008 Wiley-Liss, Inc. [source] FLT3 Antibody-based therapy for leukemiaDRUG DEVELOPMENT RESEARCH, Issue 6 2006Yiwen Li Abstract Technological advances in antibody generation and production have facilitated recent clinical and commercial success with antibody-based cancer therapeutics. The class III receptor tyrosine kinase FLT3 is highly expressed on the blast cells in most cases of acute myelogenous leukemia (AML) and B-cell acute lymphoblastic leukemia (ALL). Activating mutations of FLT3 are detected in approximately 37% AML patients. FLT3 expression in normal tissue is limited to myeloid and B-cell precursor cells. Therefore, over-expressed or mutated FLT3 is an attractive target for therapeutic intervention using monoclonal antibodies. This review will discuss recent progress in the development of anti-FLT3 antibodies as well as their therapeutic potentials in the treatment of AML and other hematological malignancies. Drug Dev. Res. 67:495,500, 2006. © 2006 Wiley-Liss, Inc. [source] Fulminant bronchiolitis obliterans organizing pneumonia following 2 d of treatment with hydroxyurea, interferon- , and oral cytarabine ocfosfate for chronic myelogenous leukemiaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2004Georgios Kalambokis Abstract:, A 65-yr-old man developed increasing dyspnea and fulminant respiratory failure 48 h after introduction of hydroxyurea, oral cytarabine ocfosfate (YNK01) and interferon- , for treatment of Philadelphia chromosome-positive chronic myelogenous leukemia. The chest radiograph showed bilateral patchy infiltrates while computed tomography revealed multiple bullas, ground glass opacities, and patchy consolidations with possible cavitation. Bronchoscopic examination was normal and microbiological tests performed on all biologic fluids were negative. The patient did not respond to multiple antibiotic treatment and corticosteroid administration and died of progressive respiratory failure 5 d after chemotherapy introduction. The postmortem lung examination was consistent with the diagnosis of bronchiolitis obliterans organizing pneumonia (BOOP). [source] Effects of angiogenic regulators on in vitro proliferation and cytokine secretion by native human acute myelogenous leukemia blastsEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2003Øystein Bruserud Abstract: Angiogenesis seems to be important in the pathogenesis of acute myelogenous leukemia (AML). The endothelial cell proliferation and microvessel formation are regulated by a wide range of soluble mediators, including angiogenin, angiopoietin-2, basic fibroblast growth factors, vascular endothelial growth factor (VEGF), VEGF-D, angiostatin and endostatin. In the present study, it has been investigated whether these mediators have an additional direct effect on the proliferation and cytokine release by native human AML blasts. AML cells derived from a large group of consecutive patients were investigated. All these mediators could alter the proliferation and cytokine release [interleukin (IL) 1,, IL6, IL8, tumor necrosis factor ,] for a minority of patients. Alteration of spontaneous proliferation by at least one mediator was detected in five of 38 patients; whereas, altered cytokine (Flt3-ligand, granulocyte-macrophage colony-stimulating factor, stem cell factor)-dependant proliferation was observed for 10 patients. Growth enhancement was most frequently observed, whereas growth inhibition was uncommon. The effects on AML blast proliferation were often dependant on or were modulated by the presence of the three hematopoietic growth factors. Based on the present results, it is concluded that angioregulatory mediators have additional growth-enhancing effects directly on the AML blasts for certain patients. However, based on the results from this investigation and previous studies it is suggested that their major contribution to the pathogenesis of AML is through their effects on regulation of bone marrow angiogenesis, and future studies of these mediators in AML should probably focus on these effects. [source] Acute megakaryocytic leukemia presenting as hypercalcemia with skeletal lytic lesionsEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2002Jeffrey H. Muler Abstract:, Acute megakaryocytic leukemia (AML M7) is a rare type of acute myelogenous leukemia in adults, commonly presenting with myelofibrosis. This report describes a case of a 32-yr-old male who presented with hypercalcemia and bony lytic lesions, in the absence of myelofibrosis. The diagnosis of AML M7 should be considered in a patient with pancytopenia, lytic lesions and hypercalcemia. [source] Comprehensive comparison of FISH, RT-PCR, and RQ-PCR for monitoring the BCR-ABL gene after hematopoietic stem cell transplantation in CMLEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5 2002Yoo-Jin Kim Abstract: The reverse transcriptase-polymerase chain reaction (RT-PCR) was compared with fluorescence in situ hybridization (FISH) and real-time quantitative RT-PCR (RQ-PCR) for minimal residual disease (MRD) monitoring in 266 post-transplant bone marrow samples from 78 patients with chronic myelogenous leukemia (CML). The sensitivities of FISH to BCR-ABL positive samples determined by first-round (1st) RT-PCR, second-round (2nd) RT-PCR, and RQ-PCR were 64.2%, 25.8%, and 20.7%, respectively. The BCR-ABL/ABL ratio by RQ-PCR had a mean of 0.000,13 in the 1st RT-PCR-negative samples and 1.42 in the 1st RT-PCR-positive samples (P<0.001), and means of 0.000,39 and 0.51 in the 2nd RT-PCR-negative and -positive samples (P< 0.001). The mean ratios of BCR-ABL/ABL by RQ-PCR were significantly different in N/N (1st/2nd RT-PCR) or N/P and P/P (P<0.001), but not in N/N and N/P, which showed that the discriminative power of RQ-PCR is confined to the 1st RT-PCR level. In this respect, monitoring of the 1st RT-PCR might be useful for estimating normalized BCR-ABL levels after transplantation. Nested RT-PCR was of limited use, as RQ-PCR quantified the BCR-ABL transcripts in 60 (91%) of 66 samples determined to be negative by 2nd RT-PCR. FISH was significantly correlated with RQ-PCR in FISH-positive samples (n=24, r=0.79, P=0.001). An increase of FISH preceded that of RQ-PCR in a few cases with molecular relapse. By analyzing a large number of samples post-transplant, we found that RQ-PCR might be the most useful assay for MRD monitoring; however, FISH and RT-PCR were found to be useful complementary tools. [source] Platelet-derived growth factor (PDGF) in human acute myelogenous leukemia: PDGF receptor expression, endogenous PDGF release and responsiveness to exogenous PDGF isoforms by in vitro cultured acute myelogenous leukemia blastsEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2001Brynjar Foss Abstract: We investigated effects of Platelet-derived growth factor (PDGF) and Platelet factor 4 (PF-4) on the functional characteristics of native, human acute myelogenous leukemia (AML) blasts. AML blast expression of the PDGF-receptor ,-chain was detected for a subset of patients (45%), whereas PDGF-receptor ,-chain expression was detected for most patients (90%). Constitutive AML blast release of the PDGF-AB isoform (the major form also derived from normal platelets) was detected for 43% of patients, whereas PDGF-BB release was not detected for any patient. The PDGF isoforms AA, AB and BB had dose-dependent and divergent effects on spontaneous and cytokine-dependent AML blast proliferation, whereas for constitutive cytokine secretion (IL-1,, IL-6, TNF-,) inhibitory effects were rare and all three isoforms usually had no effect or enhanced the constitutive secretion. The PDGF effects were caused by a direct effect on the AML blasts and were not dependent on the presence of serum. The PDGF effects could also be detected after in vitro culture of AML cells in the presence of IL-4+granulocyte-macrophage colony stimulating factor. PF-4 had divergent effects on proliferation and cytokine secretion by native AML blasts. Our results suggest that exogenous (e.g. platelet-secreted) PDGF and PF-4 can function as regulators of leukemic hematopoiesis and possibly also modulate the function of residual AML cells in peripheral blood stem cell grafts. On the other hand, endogenous release of PDGF-AB by native blasts may modulate the function of normal cells in the bone marrow microenvironment (e.g. bone marrow stromal cells). [source] High incidence of derivative chromosome arm 9q deletions in Asian chronic myelogenous leukemiaGENES, CHROMOSOMES AND CANCER, Issue 4 2005Sim-Leng Tien No abstract is available for this article. [source] The chromosome translocation t(7;11)(p15;p15) in acute myeloid leukemia results in fusion of the NUP98 gene with a HOXA cluster gene, HOXA13, but not HOXA9GENES, CHROMOSOMES AND CANCER, Issue 4 2002Takeshi Taketani The nucleoporin gene NUP98 has been reported to be fused to 9 partner genes in hematologic malignancies with 11p15 translocations. The NUP98-HOXA9 fusion gene has been identified in acute myeloid leukemia (AML) and chronic myelogenous leukemia with t(7;11)(p15;p15). We report here a novel NUP98 partner gene, HOXA13, in a patient with de novo AML having t(7;11)(p15;p15). The HOXA13 gene is part of the HOXA cluster genes and contains 2 exons, encoding a protein of 338 amino acids with a homeodomain. The NUP98-HOXA13 fusion protein consists of the N-terminal phenylalanine-glycine repeat motif of NUP98 and the C-terminal homeodomain of HOXA13, similar to the NUP98-HOXA9 fusion protein. Reverse transcriptase,polymerase chain reaction (RT-PCR) analysis in various leukemic cell lines showed that the HOXA13 gene was expressed significantly more frequently in acute monocytic leukemic cell lines than in other leukemic cell lines (P = 0.039). HOXA13 and three HOXA cluster genes (A9, A10, A11) located at the 5, end of the HOXA9 gene were frequently expressed in myeloid leukemic cell lines. Our results revealed that t(7;11)(p15;p15) was not a single chromosomal abnormality at the molecular level. The protein encoded by the NUP98-HOXA13 fusion gene is similar to that encoded by NUP98-HOXA9, and the expression pattern of the HOXA13 gene in leukemic cell lines is similar to that of the HOXA9 gene, suggesting that the NUP98-HOXA13 fusion protein may play a role in leukemogenesis through a mechanism similar to that of the NUP98-HOXA9 fusion protein. © 2002 Wiley-Liss, Inc. [source] The effects of STI571 on antigen presentation of dendritic cells generated from patients with chronic myelogenous leukemiaHEMATOLOGICAL ONCOLOGY, Issue 2 2003Naoko Sato Abstract Chronic myelogenous leukemia is caused by the acquisition of the reciprocal (9;22)(q34;q11) chromosomal translocation in hematopoietic stem cells. The fusion protein showed higher and aberrant tyrosine kinase activity. The inhibition of the tyrosine kinase activity of the protein represents a specific therapeutic strategy for bcr/abl-expressing leukemias. STI571 is a compound of the 2-phenylaminopyrimidine class that selectively inhibits the tyrosine kinase activity of the Abl protein tyrosine kinase. In this study, we evaluated the effects of STI571 on antigen presentation of dendritic cells generated from the patients with CML. The data showed that by the addition of STI571 the dendritic cells derived from CML clone showed an increased expression of CD1a, CD83, CD80 and CD86 by flow cytometry analysis and showed more intense abilities of allogeneic antigen presentation by mixed leukocyte culture, compared with the control cells without STI571. Our results suggested that STI571 not only has a direct cytotoxic effect on bcr-abl gene rearranged cells but also an indirect effect associated with increased anti-leukemic immunological function due to an intensified antigen presentation. Copyright © 2003 John Wiley & Sons, Ltd. [source] Determination of genomic copy number with quantitative microsphere hybridization,,HUMAN MUTATION, Issue 4 2006Heather L. Newkirk Abstract We developed a novel quantitative microsphere suspension hybridization (QMH) assay for determination of genomic copy number by flow cytometry. Single copy (sc) products ranging in length from 62 to 2,304 nucleotides [Rogan et al., 2001; Knoll and Rogan, 2004] from ABL1 (chromosome 9q34), TEKT3 (17p12), PMP22 (17p12), and HOXB1 (17q21) were conjugated to spectrally distinct polystyrene microspheres. These conjugated probes were used in multiplex hybridization to detect homologous target sequences in biotinylated genomic DNA extracted from fixed cell pellets obtained for cytogenetic studies. Hybridized targets were bound to phycoerythrin-labeled streptavidin; then the spectral emissions of both target and conjugated microsphere were codetected by flow cytometry. Prior amplification of locus-specific target DNA was not required because sc probes provide adequate specificity and sensitivity for accurate copy number determination. Copy number differences were distinguishable by comparing the mean fluorescence intensities (MFI) of test probes with a biallelic reference probe in genomic DNA of patient samples and abnormal cell lines. Concerted 5, ABL1 deletions in patient samples with a chromosome 9;22 translocation and chronic myelogenous leukemia were confirmed by comparison of the mean fluorescence intensities of ABL1 test probes with a HOXB1 reference probe. The relative intensities of the ABL1 probes were reduced to 0.59±0.02 &!ndash;fold in three different deletion patients and increased 1.42±0.01 &!ndash;fold in three trisomic 9 cell lines. TEKT3 and PMP22 probes detected proportionate copy number increases in five patients with Charcot-Marie-Tooth Type 1a disease and chromosome 17p12 duplications. Thus, the assay is capable of distinguishing one allele and three alleles from a biallelic reference sequence, regardless of chromosomal context. Hum Mutat 27(4), 376,386, 2006. © 2006 Wiley-Liss, Inc. [source] Solitary embolic cutaneous aspergillosis in the immunocompromised patient with acute myelogenous leukemia , a propos another case caused by Aspergillus flavusINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 12 2003Aleksandar L. Krunic MD A 68-year-old male with acute myelogenous leukemia was admitted for consolidation chemotherapy. The in-hospital course was complicated by neutropenia, fever and nodular pulmonary opacities suggestive of multifocal pneumonia. The patient subsequently developed a single, solitary necrotic crusted nodule on the right cheek. Skin biopsy demonstrated embolic vascular invasion with septate hyphae, dichotomous branching and minimal inflammation. Tissue culture revealed Aspergillus flavus. Despite systemic antifungal therapy with amphotericin B and granulocyte transfusions, the patient developed respiratory failure and died of disseminated aspergillosis, sepsis and renal failure. The clinical presentation of disseminated infection with Aspergillus flavus as a solitary embolic cutaneous lesion is extremely rare. We have reviewed other cases described in the literature and suggest this pattern of cutaneous involvement as more typical of disseminated infection with Aspergillus flavus. [source] Peripheral blood vs. bone marrow for molecular monitoring of BCR-ABL1 levels in chronic myelogenous leukemia, a retrospective analysis in allogeneic bone marrow recipientsINTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 4 2010A. BALLESTRERO Summary Molecular monitoring of the BCR-ABL1 transcript in chronic myelogenous leukemia (CML) using quantitative real-time PCR (RQ-PCR) can be performed using either bone marrow (BM) or peripheral blood (PB). However, a recent report by Stock et al. [International Journal of Oncology 28 (2006) 1099] questioned the reliability of PB samples for BCR-ABL1 detection as performed by RQ-PCR. We report a study on 114 CML patients who received allogeneic stem cell transplantation (ASCT), and who were monitored by RQ-PCR using paired samples of BM and PB: the total number of determinations was 428, with a median follow-up after transplant of 8 years. BCR-ABL1 transcript was undetectable or <0.1%, in 106 (49.57%) and 62 (29%) paired determinations, respectively. BCR-ABL1 was >0.1% in 36 (16.8%) paired determinations and was discordant in 10 (4.7%). Agreement between PB and BM results was quantified by the kappa test (k = 0.85; 95% CI 0.76,0.94). This study shows that BCR-ABL1 RQ-PCR monitoring of CML patients after ASCT with PB is concordant with BM in 95.3% of cases, and thus may be used to monitor the disease. This may be relevant when discussing both quality of life issues and the need for post-transplant monitoring with the patient. [source] Subnuclear targeting of Runx1 Is required for synergistic activation of the myeloid specific M-CSF receptor promoter by PU.1,JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 4 2005Xiangen Li Abstract Many types of acute myelogenous leukemia involve chromosomal translocations that target the C-terminus of Runx1/AML1 transcription factor, a master regulator of hematopoiesis. The C-terminus of Runx1/AML1 that includes the nuclear matrix targeting signal (NMTS) is essential for embryonic development, hematopoiesis, and target gene regulation. During the onset and normal progression of hematopoiesis, several lineage-specific factors such as C/EBP, and PU.1 interact with Runx1 to regulate transcription combinatorially. Here we addressed the functional interplay between subnuclear targeting of Runx1 and gene activation during hematopoiesis. Point mutations were generated in the NMTS of the human Runx1 protein and tested for their effect on transcriptional cooperativity with C/EBP, and PU.1 at myeloid-specific promoters. We characterized five mutants that do not alter nuclear import, DNA binding or C/EBP,-dependent synergistic activation of the target gene promoters. However a critical tyrosine in the NMTS is required for subnuclear targeting and activation of the granulocyte-macrophage colony stimulating factor (GM-CSF) promoter. Furthermore, this point mutation is defective for transcriptional synergism with PU.1 on the macrophage colony stimulating factor (MCSF) receptor c-FMS promoter. Our results indicate that the NMTS region of Runx1 is required for functional interactions with PU.1. Taken together, our findings establish that subnuclear targeting of Runx1 is a critical component of myeloid-specific transcriptional control. © 2005 Wiley-Liss, Inc. [source] Cepharanthine activates caspases and induces apoptosis in Jurkat and K562 human leukemia cell linesJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2001Jianghong Wu Abstract Cepharanthine (CEP) is a known membrane stabilizer that has been widely used in Japan for the treatment of several disorders such as anticancer therapy-provoked leukopenia. We here report that apoptosis was induced by low concentrations (1,5 ,M) of CEP in a human leukemia T cell line, Jurkat, and by slightly higher concentrations (5,10 ,M) in a human chronic myelogenous leukemia (CML) cell line K562, which expresses a p210 antiapoptotic Bcr-Abl fusion protein. Induction of apoptosis was confirmed in both Jurkat and K562 cells by DNA fragmentation and typical apoptotic nuclear change, which were preceded by disruption of mitochondrial membrane potential and were induced through a Fas-independent pathway. CEP treatment induced activation of caspase-9 and -3 accompanied by cleavage of PARP, Bid, lamin B1, and DFF45/ICAD in both Jurkat and K562 cells, whereas caspase-8 activation and Akt cleavage were observed only in Jurkat cells. The CEP-induced apoptosis was completely blocked by zVAD-fmk, a broad caspase inhibitor. Interestingly, CEP treatment induced remarkable degradation of the Bcr-Abl protein in K562 cells, and this degradation was prevented partially by zVAD-fmk. When used in combination with a nontoxic concentration of herbimycin A, lower concentrations (2,5 ,M) of CEP induced obvious apoptosis in K562 cells with rapid degradation or decrease in the amount of Bcr-Abl and Akt proteins. Our results suggest that CEP, which does not have bone marrow toxicity, may possess therapeutic potential against human leukemias, including CML, which is resistant to anticancer drugs and radiotherapy. J. Cell. Biochem. 82: 200,214, 2001. © 2001 Wiley-Liss, Inc. [source] Spontaneous nontraumatic intrasplenic pseudoaneurysm: Causes, sonographic diagnosis, and prognosisJOURNAL OF CLINICAL ULTRASOUND, Issue 3 2003Christian Görg MD Abstract Purpose The aim of this study was to describe the incidence, causes, sonographic features, therapy, and prognosis of nontraumatic intrasplenic pseudoaneurysms (NTISPs), a rare complication of splenic infarction or infiltration by malignant systemic disorders or infectious diseases. Methods We retrospectively reviewed the medical and sonographic records of all patients seen at our clinic from July 1985 through December 2000 to identify patients with a sonographic diagnosis of spontaneous nontraumatic splenic rupture. We then examined the features of the resulting cases to identify patients in whom NTISPs were revealed by color Doppler sonography. Results In total, 41 patients were identified. Among those patients, 5 (12%) had NTISPs. Three of those 5 patients had an underlying malignant disorder (1 case of non-Hodgkin's lymphoma and 2 cases of chronic myelogenous leukemia), and the other 2 had an inflammatory disease (1 case of endocarditis and 1 case of pancreatitis). Three of the patients also had splenic infarctions. Three patients underwent splenectomy; in 2 of them, secondary delayed splenic rupture occurred before or during splenectomy. In 2 other patients, spontaneous thrombosis of the aneurysms occurred (after 16 hours in 1 and 15 days in the other). Conclusions NTISPs may occur in about 12% of patients with sonographically detected nontraumatic spontaneous splenic rupture. NTISPs appear to be associated with an increased risk of secondary delayed splenic rupture, although spontaneous thrombosis may occur. Short-term follow-up sonographic examinations, particularly with color Doppler imaging, are recommended for early recognition of progression of NTISPs, which can guide treatment decisions. © 2003 Wiley Periodicals, Inc. J Clin Ultrasound 31:129,134, 2003 [source] C-KIT expression in primary cutaneous T-cell lymphomasJOURNAL OF CUTANEOUS PATHOLOGY, Issue 9 2004Tilmann C. Brauns Background:, Mutations of the stem cell factor receptor C-KIT play a major pathogenetic role in the development of different malignant diseases like human mastocytosis, myeloproliferative disorders, gastrointestinal stromal tumors, acute myelogenous leukemia, and sinonasal lymphomas. Furthermore, the expression of C-KIT has been described in Hodgkin's disease and nodal CD30+ anaplastic large cell lymphomas (ALCLs). As it is possible to inhibit C-KIT by innovative kinase inhibitors like STI571, it may be an attractive target for new therapeutical approaches. Therefore, we screened more than 50 different types of cutaneous T-cell lymphomas (TCLs) for the presence of C-KIT. Immunohistochemical stainings were performed on paraffin-embedded tissue sections using a polyclonal rabbit anti-human C-KIT antibody. Naphtol-ASD-chloroacetate esterase (NASDCE)-control stainings were performed on every positive sample to distinguish C-KIT-positive lymphoma cells from C-KIT-positive mast cells. Results:, We found weak expression of C-KIT in seven of 18 patients with primary cutaneous CD30+ ALCL, two of eight patients with primary cutaneous pleomorphic TCL, six of 18 patients suffering from mycosis fungoides, and three of five patients with Sezary's syndrome. Generally, only a very small population of the lymphoma cells expressed C-KIT. This finding indicates a difference to the systemic variant of CD30+ ALCL. The potential use of C-KIT targeting new therapeutical approaches is therefore discussed critically, because C-KIT expression is very rare in all investigated types of primary cutaneous lymphoma. [source] Tyrosine kinase inhibitors: From rational design to clinical trialsMEDICINAL RESEARCH REVIEWS, Issue 6 2001Peter Traxler Abstract Protein kinases play a crucial role in signal transduction as well as in cellular proliferation, differentiation, and various regulatory mechanisms. The inhibition of growth related kinases, especially tyrosine kinases, might provide new therapies for diseases such as cancer. The progress made in the crystallization of protein kinases has confirmed that the ATP-binding domain of tyrosine kinases is an attractive target for drug design. Three successful examples of drug design at Novartis using a tyrosine kinase as a molecular target are described. PKI166, a pyrrolo[2,3,- d]pyrimidine derivative, is a dual inhibitor of both the EGFR and the ErbB2 kinases. The compound entered clinical trials in 1999, based on its favorable preclinical profile: potent inhibition of EGF-mediated signalling in cells, in vivo antitumor activity in several EGFR overexpressing xenograft tumor models in nude mice, long-lasting inhibition of EGF-stimulated EGFR autophosphorylation in tumor tissue, good oral bioavailability in animals, and no prohibitive in vitro and in vivo toxicity findings. The anilino-phthalazine derivative PTK787/ZK222584 (Phase I, co-developed by Schering AG, Berlin) is a potent and selective inhibitor of both the KDR and Flt-1 kinases with interesting anti-angiogenic and pharmacokinetic properties (orally bioavailable). STI571 (GlivecÔ, GleevecÔ), a phenylamino-pyrimidine derivative, is a potent inhibitor of the Abl tyrosine kinase, which is present in 95% of patients with chronic myelogenous leukemia (CML). The compound specifically inhibits proliferation of v-Abl and Bcr-Abl expressing cells (including cells from CML patients) and shows anti-tumor activity as a single agent in animal models at well-tolerated doses. Pharmacologically relevant concentrations are achieved in the plasma of animals (oral administration). Promising data from phase I and II clinical trials in CML patients (98% haematological response rate in Phase I) support the fact that the STI571 represents a new treatment modality for CML. In addition, potent inhibition of the PDGFR and c-Kit tyrosine kinases also indicates its possible clinical use in solid tumors. © 2001 John Wiley & Sons, Inc. Med Res Rev, 21, No. 6, 499,512, 2001 [source] Sequence of administration and methylation of SOCS3 may govern response to gemtuzumab ozogamicin in combination with conventional chemotherapy in patients with refractory or relapsed acute myelogenous leukemia (AML),AMERICAN JOURNAL OF HEMATOLOGY, Issue 7 2010Iris Middeldorf In older patients suffering from acute myelogenous leukemia (AML), aggressive chemotherapy is accompanied with high treatment-related morbidity and mortality. Gemtuzumab ozogamicin (GO), a humanized monoclonal anti-CD33 antibody, represents a well tolerated treatment option, but optimal treatment schedules are still unknown. Additionally, Suppressor of cytokine signaling 3 (SOCS3) inhibits the CD33-induced block on cytokine-induced proliferation. Consequently, a variable response of AML cells to anti-CD33-targeted therapy may be caused by modulation of SOCS3 expression. Twenty-four patients with refractory or relapsed CD33-positive AML received GO as a single agent before or after conventional chemotherapy. The methylation status of the SOCS3 CpG island was assessed by methylation-specific polymerase chain reaction. Response (RR) and overall survival (OS) were significantly higher in 16 patients receiving chemotherapy before GO (RR 81%, OS 14.8 months) compared to three patients who received GO single agent therapy (RR 33%, OS 7.2 months) or 16 with GO before chemotherapy (RR 0% OS 2.2 months, P = 0.01 for RR and P < 0.001 for OS). Methylation of the SOCS3 CpG island was found in 8/24 patients. There was a trend towards a higher RR and longer OS in patients with SOCS3 hypermethylation (RR 86%, OS 25.1 months) compared to unmethylated SOCS3 (RR 56%, OS 10.3 months, P = 0.09). Administration of GO a few days after chemotherapy seems to provide better response and survival compared to administration of GO directly before chemotherapy. The potential role of SOCS3 hypermethylation as a biomarker should be further investigated in patients undergoing GO containing therapies. Am. J. Hematol., 2010. © 2010 Wiley-Liss, Inc. [source] The assessment of human organic cation transporter 1 (hOCT1) mRNA expression in patients with chronic myelogenous leukemia is affected by the proportion of different cells types in the analyzed cell population,AMERICAN JOURNAL OF HEMATOLOGY, Issue 7 2010Zdenek Racil First page of article [source] Persistent splenomegaly during imatinib therapy and the definition of complete hematological response in chronic myelogenous leukemia,AMERICAN JOURNAL OF HEMATOLOGY, Issue 5 2010Zdenek Racil First page of article [source] Dasatinib 140 mg once daily versus 70 mg twice daily in patients with Ph-positive acute lymphoblastic leukemia who failed imatinib: Results from a phase 3 study,,AMERICAN JOURNAL OF HEMATOLOGY, Issue 3 2010Michael B. Lilly Dasatinib 70 mg twice daily is indicated for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) intolerant or resistant to imatinib. In patients with chronic-phase chronic myelogenous leukemia, once-daily dosing has similar efficacy with improved safety, compared with twice-daily dosing. A phase 3 study (n = 611) assessed the efficacy and safety of dasatinib 140 mg once daily versus 70 mg twice-daily in patients with advanced phase chronic myelogenous leukemia or Ph+ ALL resistant or intolerant to imatinib. Here, results from the Ph+ ALL subset (n = 84) with a 2-year follow-up are reported. Patients were randomly assigned to receive dasatinib either 140 mg once daily (n = 40) or 70 mg twice daily (n = 44). The rate of confirmed major hematologic response with once-daily dosing (38%) was similar to that with twice-daily dosing (32%). The rate of major cytogenetic response with once-daily dosing (70%) was higher than that with twice-daily dosing (52%). Compared with the twice-daily schedule, the once-daily schedule had longer progression-free survival (median, 3.0 months versus 4.0 months, respectively) and shorter overall survival (median, 9.1 months versus 6.5 months, respectively). Overall safety profiles were similar between two groups, with nonhematologic adverse events being mostly grade 1 or 2. Pleural effusion was less frequent with once-daily dosing than with twice-daily dosing (all grades, 18% versus 32%). Notably, none of the differences between the two schedules was statistically significant. Compared with the 70 mg twice daily, dasatinib 140 mg once daily had similar overall efficacy and safety in patients with imatinib-resistant or intolerant Ph+ ALL. (clinicaltrials.gov identifier: NCT00123487). Am. J. Hematol. 2010. © 2009 Wiley-Liss, Inc. [source] Pseudohypopyon: Extramedullary relapse of acute myelogenous leukemia with poor prognosisPEDIATRIC BLOOD & CANCER, Issue 7 2009William C. Petersen MD Abstract An 11-month-old female presented to the emergency department with a 2-week history of fever, increasing fussiness, emesis, and decreased urine output. She was diagnosed with acute myelogenous leukemia. Systemic chemotherapy with intensified intrathecal cytarabine was started, and the patient achieved a clinical remission after the first course of induction. Towards the end of her second course of induction she developed pseudohypopyon in each eye on consecutive days, heralding a central nervous system relapse. Pediatr Blood Cancer 2009;52:885,887. © 2008 Wiley-Liss, Inc. [source] Treatment of CML in pediatric patients: Should imatinib mesylate (STI-571, Gleevec) or allogeneic hematopoietic cell transplant be front-line therapy?PEDIATRIC BLOOD & CANCER, Issue 5 2004Michael A. Pulsipher MD Abstract Background Long-term survival of pediatric patients with chronic myelogenous leukemia (CML) receiving myeloablative hematopoietic stem cell transplantation from fully-matched related and unrelated donors has been reported between 60 and 75%, but is associated with significant morbidity. Imatinib mesylate (STI-571, Gleevec) and reduced intensity conditioning stem cell transplantation (RIC) are two promising new tools that offer potential for decreasing therapy associated morbidity for patients with CML. Results Large trials have shown significant responses in chronic phase patients treated with imatinib and reasonable but short-lived responses in advanced phase CML. Data from adult studies is beginning to define populations likely to progress or have prolonged responses to imatinib, and some adult treatment paradigms are moving toward reserving transplantation until patients are at risk of failure with imatinib. Early trials of RIC transplantation in CML show decreased transplant related morbidity with efficacy similar to conventional transplantation, but the approach has yet to be verified in phase III studies. Data in pediatric patients with imatinib and RIC transplantation is limited. Conclusions Studies with imatinib are underway in pediatrics, but whether pediatric dosing schemes will lead to outcomes similar to adults is unknown. Because HLA-matched myeloablative transplantation offers a high rate of cure in the pediatric population, clinical studies assessing the role of imatinib mesylate and RIC transplantation should be planned carefully in order to avoid sub-optimal outcomes. © 2004 Wiley-Liss, Inc. [source] A homoharringtonine-based regimen for childhood acute myelogenous leukemiaPEDIATRIC BLOOD & CANCER, Issue 1 2003JingYan Tang MD No abstract is available for this article. [source] Cutaneous zygomycosis caused by Cunninghamella bertholletiae in a patient with chronic myelogenous leukemia in blast crisis,AMERICAN JOURNAL OF HEMATOLOGY, Issue 7 2009Kenji Motohashi No abstract is available for this article. [source] | |||||||||||||||||||||||||||||||||||||