UMLS:C0026986 - FACTA Search

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Query: UMLS:C0026986 (myelodysplastic syndrome)
14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

After a single pulse dose of DMBA, rats develop bone-marrow hypoplasia, which is almost compensated for by regeneration after 16 weeks. Subsequently, dysplastic signs of hemopoiesis appear in all experimental animals as massive extrusion of normoblasts into the peripheral blood, red-cell aniso- and poikilocytosis, nuclear deformities, atypical mitoses, and PAS-positivity, as well as megaloblastoid maturation dissociation of erythroblasts and nuclear and granulation anomalies of neutrophilic granulocytes and monocytes, comparable to human "pseudo-Pelger cells" and "paraneutrophils". At the time of death (112-497 days after DMBA pulse) experimental animals showed hyperplastic bone marrow with increased granulopoietic/erythropoietic ratios and an augmented, mainly erythropoietic, hemopoiesis in the spleen, with splenomegaly in six rats. Splenic hemopoiesis is accompanied by white pulp atrophia. The cause of death was septicopyemia in three rats, anemia in three, and bleeding in one rat. None of the animals developed a leukemic blast phase. Myelodysplastic changes in this experiment are the same as have been shown to precede leukemia in rats treated with five DMBA pulses (Fohlmeister et al. 1981). Possible relations of myelodysplasia and leukemia are discussed.
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PMID:On the pathogenesis of preleukemic myelodysplastic syndromes: development of a dysplastic hemopoietic proliferation in the rat after a single pulse dose of dimethylbenz(a)anthracene (DMBA). 681

The c-kit proto-oncogene is the receptor gene for the stem cell growth factor. Little is known about the distribution and role of this gene product in malignant hematopoiesis. We analysed here the expression of c-kit in myeloproliferative disorders (MPDs), including chronic myelogenous leukemia (CML), essential thrombocythemia (ET), polycythemia vera (PV), and idiopathic myelofibrosis (IMF) and in the myelodysplastic syndromes (MDS). The c-kit expression of peripheral blood mononuclear cells was measured both at the messenger RNA level using Northern analysis, the RNA dot blot technique with densitometric quantification, the sensitive reverse transcription polymerase chain reaction, and at the protein level using immunofluorescence with monoclonal antibodies. There was a statistically significant increase in c-kit messenger levels in CML, ET, PV, IMF, and MDS as compared with controls (healthy volunteers). The percentage of c-kit protein expressing cells was also higher than in the controls in these disorders. There was a significant correlation of the c-kit protein expression with the CD34 antigen of the cells. Expression correlated with the phase of the disease, being highest in the blast crisis of CML and in the RAEB/RAEBt phases of MDS. The data suggest that increased amounts of circulating stem/progenitor cells with c-kit receptor are found in MPDs and MDS. It is possible that elevated c-kit expression could maintain the affected clone in MPDs and MDS.
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PMID:Expression of the c-kit proto-oncogene in myeloproliferative disorders and myelodysplastic syndromes. 751 74

We previously reported the cloning, and characterization of a receptor tyrosine kinase, axl, from two patients with chronic myelogenous leukemia. Herein, we describe the expression pattern of axl in normal and malignant hematopoietic tissue axl message is detected in normal human bone marrow but not significantly in normal blood leukocytes. Cell separation experiments showed that axl is expressed in hematopoietic CD34+ progenitor and marrow stromal cells, at low levels in peripheral monocytes, but not in lymphocytes or granulocytes. Consistent with the normal pattern of axl expression, axl RNA was found predominantly in diseases of the myeloid lineage: 39 of 66 (59%) patients with myeloproliferative disorders (acute myeloid leukemia, chronic myeloid leukemia (CML) in chronic phase, CML in myeloid blast crisis, and myelodysplasia) showed significant axl transcription, as compared with 1 of 45 (2%) lymphoid leukemias (chronic lymphocytic leukemia, acute lymphocytic leukemia, and CML in lymphoid blast crisis). Treatment of K562 cells with the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), administration of interferon alpha (IFN alpha) to normal monocytes, and treatment of U937 cells with TPA and IFN tau significantly induced axl expression, supporting a role for this kinase in the intracellular signaling of myeloid cells through a variety of biochemical pathways. These results suggest that the axl kinase may be operative in normal and malignant myeloid biology.
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PMID:Expression of axl, a transforming receptor tyrosine kinase, in normal and malignant hematopoiesis. 752 95

Autonomous, factor-independent growth and differentiation of malignant cells in preleukemic and leukemic disease states is a well-recognized phenomenon and is often associated with a poor prognosis. Mast cells are distinct hematopoietic cells and express a unique profile of antigens. Growth and differentiation of normal mast cells is dependent on mast cell growth factor (MGF), the ligand of the c-kit protooncogene product. In this study, we screened for mast cell-lineage involvement in 52 patients suffering from myeloid leukemias, myelodysplastic syndromes (MDS), systemic mastocytosis, or other diseases by probing for mast cell-related molecules (c-kit, tryptase, histamine, and MGF) and by analyzing kit ligand/MGF-independent growth of mast cells in long-term suspension culture. Of the 52 patients tested, 2 patients with refractory anemia with excess of blast cells in transformation and 1 patient suffering from chronic myeloid leukemia blast crisis (CML-BC) were diagnosed as mastocytic disease. These patients were characterized by complex chromosomal abnormalities, splenomegaly, high percentages of circulating metachromatic cells (5% to 25%), high levels of cellular tryptase (> 10 ng/10(5) peripheral blood mononuclear cells/mL) and a tryptase/histamine (ng:ng) ratio greater than 1. The metachromatic cells expressed the mast-cell-related surface antigen c-kit, but not basophil-related antigens (CD11b, CDw17). Furthermore, in these 3 patients, spontaneous, MGF-independent growth of mast cells along with spontaneous synthesis of tryptase was demonstrable in long-term culture. No autocrine production, paracrine production, or overproduction of MGF was found. The spontaneous growth of mast cells could neither be abbrogated by addition of monoclonal antibodies (MoAbs) to c-kit nor by MoAbs against MGF (< 5% inhibition), whereas factor (MGF)-dependent differentiation of mast cells in these patients could be abbrogated by MoAbs to c-kit or MoAbs to MGF (> 70% inhibition, P < .001). In addition, serum MGF levels in these patients were within the normal range and MGF could not be detected in cell-free culture supernatants. All 3 patients showed rapid progression of disease and had a survival time of less than 1 year. In conclusion, we describe a unique form of transformation in MDS and CML-BC characterized by mast cell lineage involvement and factor-independent differentiation of mast cells. This form of leukemic transformation has to be delineated from chronic myeloid leukemia with basophilia or basophil crisis, from primary mast cell leukemia, and from monocytic leukemias and myelodysplastic disorders associated with basophilia.
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PMID:Kit ligand/mast cell growth factor-independent differentiation of mast cells in myelodysplasia and chronic myeloid leukemic blast crisis. 752 72

The t(3;21)(q26;q22) is associated with chronic myelogenous leukemia in blast crisis (CML-BC), leukemia evolving from (therapy-related) myelodysplasia, and with leukemia following other hematopoietic proliferative diseases. Molecular cytogenetic analysis and cloning of a few t(3;21) cases indicate that the breakpoints are quite heterogeneous even within a specific clinical phenotype. Interestingly some of the (3;21) breakpoints involve the AML1 gene previously found rearranged in the t(8;21) associated with acute myelogenous leukemia. AML1 is related to the Drosophila gene runt and is the human counterpart of the gene for the alpha subunit of the nuclear polyoma enhancer binding protein (PEBP2) also known as the core binding factor (CBF). In the t(3;21) AML1 was found rearranged with EAP, a gene on chromosome 3 encoding a small ribosomal protein, as well as with EV11, another gene on chromosome 3. Here we report our study of six cases of t(3;21). By using fluorescence in situ hybridization (FISH) analysis and AML1 probes we could conclude that at least in two CML-BC cases the breakpoint occurred in the AML1 intron that is disrupted by the t(8;21). An AML1/EAP fusion transcript, different from the one described in a therapy-related myelodysplasia, was detected in both CML-BC cases. This transcript is expected to result in a predicted protein containing the AML1 nuclear binding domain with an attached stretch of 17 amino acids unrelated to the EAP small ribosomal protein. In the other t(3;21) patients we could not detect an AML1/EAP transcript or an AML1/EV11 transcript. This result suggests heterogeneity of the t(3;21) at the molecular level. The AML1 chimeric transcripts identified so far, both in the t(3;21) and in the t(8;21), diverge from the normal transcripts either after exon 5 or exon 6. Here we show that in normal AML1 transcripts different splicing events are seen to occur after AML1 exon 5 as well as exon 6.
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PMID:AML1 fusion transcripts in t(3;21) positive leukemia: evidence of molecular heterogeneity and usage of splicing sites frequently involved in the generation of normal AML1 transcripts. 753 26

A monoclonal antibody which primarily reacted with Philadelphia chromosome (Ph1)-positive ALL cells was produced. The reactivity of a monoclonal antibody, KOR-SA3544 (IgG2a) was evaluated on normal hemopoietic cells, 68 leukemic cell lines and freshly obtained cells from 190 patients with leukemia and lymphoma. In cultured cells, KOR-SA3544 reacted with Ph1-positive ALL cell lines (5/5) and leukemic cell lines with 11q23 translocation (3/11). In lymphoid cells, KOR-SA3544 was reactive with all of Ph1-positive ALL (26/26), a part of common ALL (5/38) and one case of early B precursor leukemia with 11q23 translocation, but not with peripheral lymphocytes. Normal mature granulocytes were also strongly stained. In myeloid leukemias, KOR-SA3544 was positive (16/56) only in patients with acute myeloid leukemia with FAB-M2 and overt leukemia following myelodysplastic syndrome, but neither with other types of myeloid leukemias nor with blast crisis in chronic myelogenous leukemia. KOR-SA3544 recognized a 90 KDa protein on the membrane of a leukemic cell line, KOPN-57bi. In normal bone marrow, CD19+/KOR-SA3544+ cells were not identified, while Ph1-positive ALL cells were strongly positive for both antibodies. KOR-SA3544 is useful not only for making the diagnosis of Ph1-positive ALL but for detection of the minimal residual disease during remission.
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PMID:A novel monoclonal antibody, KOR-SA3544 which reacts to Philadelphia chromosome-positive acute lymphoblastic leukemia cells with high sensitivity. 754 76

Juvenile chronic myelogenous leukemia (JCML) is a heterogeneous disorder composed of Philadelphia chromosome-positive (Ph+) CML, which is similar to CML in adults, and Ph-negative (Ph-) CML, a childhood myelodysplasia resembling chronic myelomonocytic leukemia in adults. These two disorders are not always readily separable by leukocyte alkaline phosphatase (LAP) scoring and by karyotyping, yet they have different courses and outcomes. We compared the results of breakpoint cluster region (bcr) gene rearrangement analysis with LAP score and karyotype in these patients. In addition, analysis for immunoglobulin and T-cell receptor gene rearrangement was done to investigate the possibility of mixed myeloid and lymphoid lineage, which has been shown to occur in childhood acute myelogenous leukemia and CML in blast crisis. Peripheral blood and bone marrow samples from six patients with JCML aged 5 to 19 yr were analyzed. One case was Ph+, and five were Ph- by karyotyping. Two samples showed LAP scores of 5 and 11 (one Ph+ and one Ph-); others were normal. All were digested with EcoRI, HindIII, and BamHI for immunoglobulin heavy and light chains and T-cell receptor beta-chain analysis and, in addition, with BglII for bcr analysis. Samples were hybridized with probes to JH, JK, CT beta, and bcr (Oncor). A bcr rearrangement was shown in the Ph+ sample; all others, including one with a very low LAP score, were negative. No JH, JK, or CT beta rearrangements were detected.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Breakpoint cluster region, immunoglobulin, and T-cell receptor gene rearrangement analysis in juvenile chronic myelogenous leukemia. 756 36

If chronic myelomonocytic leukemia (CMML) transforms into an acute leukemic phase, the blast crisis is invariably myeloid. Occasionally, the other subtypes of myelodysplastic syndrome (MDS) (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation) have been noted to transform into acute lymphoblastic leukemia (ALL). We now report a case of CMML that transformed into ALL and we review the literature of 13 other cases of MDS with ALL transformation. Such cases provide suggestive clinical evidence that MDS can involve a pluripotent stem cell.
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PMID:Transformation of chronic myelomonocytic leukemia to acute lymphoblastic leukemia: case report and review of the literature of lymphoblastic transformation of myelodysplastic syndrome. 777 69

We investigated expression of the human ecotropic virus integration site-1 (EVI1) gene in patients with leukemia and myelodysplastic syndrome (MDS) using the reverse transcriptase-polymerase chain reaction (RT-PCR) method. The EVI1 transcripts were detected in 5 (10.0%) of 50 patients with de novo acute myeloid leukemia (AML), including two AML patients with trilineage myelodysplasia, and in 8 (34.8%) of 23 patients with post-myelodysplastic syndrome AML (post-MDS AML). EVI1 expression was also detected in 6 (35.3%) of 17 MDS patients and three of six patients with chronic myeloid leukemia (CML) in myelomegakaryoblast crisis. No EVI1 transcripts were detected in patients with acute lymphoid leukemia (n = 15) or CML in lymphoid blast crisis (n = 4). Chromosomal abnormalities at the 3q26 region, where the EVI1 gene is located, were found in one patient with MDS and two patients with CML myelomegakaryoblast crisis who had EVI1 expression. Our results showed that EVI1 expression was frequent in patients with post-MDS AML and AML with trilineage myelodysplasia, regardless of the presence or absence of 3q26 abnormalities. EVI1 expression was accompanied by expression of GATA-1 and GATA-2, and often by stem cell leukemia (SCL) gene expression. In patients with post-MDS AML, EVI1 expression was not always associated with a 3q26 abnormality, whereas EVI1 expression in CML myelomegakaryoblast crisis was often linked to a 3q26 abnormality. Our results suggest that the leukemogenic role of EVI1 expression may differ between post-MDS AML and leukemia, with EVI1 expression associated with a 3q26 abnormality.
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PMID:Ecotropic virus integration site-1 gene preferentially expressed in post-myelodysplasia acute myeloid leukemia: possible association with GATA-1, GATA-2, and stem cell leukemia gene expression. 778 Jan 55

We have previously shown that long-term cultures of adherent layers derived from patients with chronic myelogenous leukemia in blast crisis express high levels of interleukin (IL)-1 beta and that this cytokine may participate in disease progression. In this study, we analyzed cytokine expression in bone marrow adherent layers derived from patients with myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML). IL-6 messenger RNA (mRNA) was expressed in adherent layers established from four of nine MDS patients, and from 10 of 17 AML patients (including all four individuals in whom AML had evolved from an antecedent MDS state). Similarly, IL-1 beta mRNA was expressed in adherent layers derived from two of nine MDS patients and from three of 17 AML patients. Cultures from two of 10 AML patients who expressed IL-6 also expressed granulocyte (G) colony-stimulating factor (CSF) mRNA. In contrast, IL-1 beta, IL-6, and G-CSF mRNA were not discernible in adherent layers from any of 14 normal volunteers. Transforming growth factor-beta 1, macrophage (M) CSF, IL-7, and leukemia inhibitory factor mRNA as well as IL-6 protein were constitutively expressed in adherent layers derived from both MDS patients, AML patients, and normal bone marrows, whereas IL-1 alpha, tumor necrosis factor-alpha, and GM-CSF were not expressed in either the normal-, MDS- or AML-derived adherent layers. These results indicate that cultured stroma from a subset of MDS and AML patients produce IL-1 beta and/or IL-6. Although, exposure of adherent layers to exogenous IL-1 beta was able to induce IL-6 expression, in 9 of the 14 samples constitutively expressing cytokines, IL-6 transcript levels were elevated without a concomitant increase in IL-1 beta, suggesting that IL-6 transcription was independently dysregulated.
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PMID:Cytokine expression in adherent layers from patients with myelodysplastic syndrome and acute myelogenous leukemia. 783 15

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