Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Morphologic, immunologic, and cytogenetic features were studied in 30 newly diagnosed patients with CD34-positive (CD34+) de novo acute myeloid leukemia (AML) in comparison with 30 patients with CD34-negative (CD34-) AML. Karyotype at diagnosis was abnormal in 25/30 CD34+ AML patients, of which nine had major karyotype aberrations (MAKA). Clonal chromosome changes were detected in 9/30 patients with CD34- AML. The most frequent chromosome aberration in CD34+ patients was -5/5q-, an aberration showing a strong association with the M2 FAB subtype of AML. Other recurring chromosome changes involved chromosome 16q (four cases) and chromosome 17p (three cases). Total or partial monosomy 7q was detected in three cases. Among CD34- AML, two patients had the classical t(15;17) and two had structural aberrations of 6q. Among patients with CD34+ AML, nine had MAKA in association with trilineage myelodysplasia (TMDS). TMDS was infrequent in CD34+ AML without MAKA and in CD34- AML. Complete remission (CR) was achieved in 8/30 CD34+ AML (26%), as compared with 22/30 CD34- AML (73%), and median survival was 2 months in the former group and 8 months in the latter. No patient with CD34+ AML and MAKA achieved CR, whereas 8/21 CD34+ AML without complex chromosome changes or with normal karyotype achieved CR. In conclusion, a distinct cytogenetic profile may be associated with CD34+ AML. Cytogenetic findings in CD34+ AML may be clinically relevant in that they may disclose a subset of patients with MAKA with a low CR rate.
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PMID:Chromosome aberrations in CD34-positive acute myeloid leukemia. Correlation with clinicopathologic features. 750 35

The in vitro colony-forming capacities of marrow CD34-positive (CD34+) cells from 25 patients with myelodysplastic syndromes (MDS) were studied. In all patients this purified cell population showed erythroid (burst-forming unit erythroid; BFU-E) or non-erythroid colony growth, both of which were more restricted than non-purified mononuclear cell population under stimulation with erythropoietin (EPO) or granulocyte/macrophage colony-stimulating factor (GM-CSF) alone. MDS patients examined were put into two groups; refractory anemia (RA) or RA with ringed sideroblasts (RA/RARS) and RA with excess of blasts (RAEB) or RAEB in transformation (RAEB/RAEB-t). The CD34+ cells of both RA/RARS and RAEB/RAEB-t exhibited a similarity to the cells of normal individuals in their responsiveness to the addition of interleukin 6 (IL-6), IL-3 or stem cell factor (SCF). SCF caused powerful but highly variable responses in both erythroid and nonerythroid colony formation as compared with IL-6 or IL-3. We demonstrated that MDS marrow hematopoietic progenitor cells reactive to GM-CSF or EPO were additionally stimulated with early-acting hematopoietic growth factors including IL-6, IL-3 and SCF in a fashion similar to those of normal individuals.
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PMID:Growth analysis of marrow CD34-positive hematopoietic progenitor cells in patients with myelodysplastic syndromes. 751 49

Bone marrow (BM) biopsies from 58 patients with primary myelodysplastic syndrome (MDS) were studied using QBEND10, a monoclonal antibody that recognizes the human progenitor CD34 antigen in routine aldehyde-fixed paraffin-embedded samples. FAB subtypes were RA (5 patients), RARS (9 patients), RAEB (20 patients), RAEBt (11 patients), CMML (3 patients). In addition, 10 MDS patients whose BM biopsies revealed heavy reticulum fibrosis were included. Neither the percentage of CD34+ cells nor the number of CD34+ aggregates (defined as clusters of 3 or more cells) correlated with the presence and morphology of abnormal localizations of immature precursors (ALIP). When all patients were considered, median survival was 69 months in those with less, and 25 months in patients with more than 1% CD34+ cells (P < 0.05). Median survival was 15 months in patients with CD34+ aggregates and 41 months in those without aggregates (P = 0.0017). When RAEB patients were considered median survival was 41 months in those with less than 1%, and 29 months in those with more than 1% CD34+ cells; the 4-year survival chance was 45% in the former and 18.3% in the latter group. Therefore, CD34 positivity of more than 1% identifies a subset of RAEB patients with shorter life expectancy. In addition, leukemic transformation was observed in 11 of 35 patients (31%) with no CD34 aggregates, but in 14 of 23 patients (60%) with aggregates (P < 0.05). CD34 immunostaining, which can be easily performed on routinely prepared BM biopsies, was found to be a powerful prognostic tool for predicting survival and outcome in MDS.
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PMID:CD34 immunohistochemistry of bone marrow biopsies: prognostic significance in primary myelodysplastic syndromes. 751 57

To evaluate the effects of colony-stimulating factors (CSFs) on pathological cells from myelodysplastic syndromes (MDS), the blast cells from 19 MDS patients (eight low-risk MDS, six high-risk MDS, and five leukemic transformation of MDS [LT-MDS]) and four normal volunteers were successfully enriched by separating CD34-positive cells by the use of immunomagnetic beads, and their responsiveness to granulocyte or granulocyte-macrophage CSF (G-CSF or GM-CSF) was examined in short-term liquid suspension culture. The proliferation of MDS blast cells was clearly promoted by these CSFs in all cases examined, but considerable percentages of them often remained immature compared with the favorable maturation of normal blast cells, especially in the more advanced disease groups (LT-MDS and high-risk MDS) that included two prominent cases with a remarkable blast cell growth without maturation induction by CSFs. The expression of esterase activities was rather sluggish in the MDS cases, in contrast to normal expression. These data showed that MDS blast cells proliferate in response to CSFs but that maturation is less than that observed with normal blast cells in vitro. Much care should be taken with in vivo application of CSFs to high-risk MDS patients.
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PMID:Altered responses of purified blast cells from the myelodysplastic syndromes to colony-stimulating factors in vitro: comparison with normal blast cells. 751 87

Immunological analysis of bone marrow cells in myelodysplasia using immunofluorescence did not allow accurate morphological identification of blast cells. However, improvement of the immunoperoxidase technique allows one to realize the diagnostic potential of immunocytochemistry. CD34 immunotyping of blasts in normal human bone marrow showed 0.8 +/- 0.4% CD34 positive blasts and these cells had the morphology of type 1 blasts. The increase of bone marrow blasts in RAEB patients is related to CD34 negative type II and III blasts. A clone of undifferentiated CD34 positive blasts is characteristic of RAEB-T and acute myeloid leukaemia evolving from myelodysplasia. The detection of CD34 positive bone marrow blasts allows a better discrimination between RAEB and RAEB-T.
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PMID:CD34 immunophenotyping of blasts in myelodysplasia. 753 58

To investigate the role of colony stimulating factors (CSFs) in the proliferation and differentiation of progenitor cells from myelodysplastic syndromes (MDS), marrow progenitor cells from 18 MDS patients were highly purified using CD34 monoclonal antibody and immunomagnetic microspheres (MDS CD34+ cells). These cells were cultured in serum-free medium with various combinations of five colony stimulating factors (CSFs): recombinant human interleukin-3 (rIL-3), granulocyte/macrophage-CSF (rGM-CSF), granulocyte-CSF (rG-CSF), macrophage-CSF (rM-CSF), and erythropoietin (rEP). Among the tested CSFs, such as rM-CSF, rG-CSF, rGM-CSF and rIL-3, a combination of the first three CSFs was the most effective stimulus for the proliferation of non-erythroid MDS progenitor cells. An increase of undifferentiated "blast" cell colonies in 5/18 MDS patients occurred and these 5 patients belonged to the high-risk group. In the presence of these three CSFs, rIL-3 had no effect on the proliferation and differentiation of MDS CD34+ cells; however, IL-3 was efficient for the proliferation of MDS CD34+ cells to the erythroid lineage. rGM-CSF or rIL-3 alone did not efficiently support proliferation and differentiation of CD34+ cells. M-CSF is present in normal human serum at a concentration of 550 +/- 110 U/ml, a concentration exceeding that used in this study (100 U/ml). Therefore, in vivo administration of G-CSF combined with GM-CSF to MDS patients may be one of the most effective CSF combinations for proliferation of MDS progenitor cells to the non-erythroid lineage. However, the effect on the capacity for differentiation was minimal, especially in patients belonging to the high-risk group.
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PMID:Proliferation and differentiation of myelodysplastic CD34+ cells in serum-free medium: II. Response to combined colony-stimulating factors. 753 45

To evaluate the clinical relevance of multidrug resistance (MDR) phenotype, the intracellular daunorubicin accumulation (IDA) and P-glycoprotein (P-gp) expression were investigated in 87 adult patients with acute leukemia: 69 patients with de novo acute myeloid leukemia (AML), 10 with AML at relapse, and eight with secondary leukemia to myelodysplastic syndromes (MDS-AML). IDA and P-gp expression were determined by double-labeling flow cytometry analysis. Of 87 patients, 36 expressed P-gp (41%). P-gp expression was more frequently observed in AML at relapse and MDS-AML as compared with de novo AML (P = .0001). P-gp expression was significantly associated with CD34 expression (P = .0003) and chromosome 7 abnormalities (P = .027). A significantly reduced IDA was observed in P-gp+ as compared with P-gp- patients (P = .0007). Of the 87 patients, 51 achieved complete remission (CR). A reduced IDA was observed in patients in failure as compared with patients in CR (22% +/- 17% v 42% +/- 21%; P = 10(-4). Twelve of 36 P-gp+ patients as compared with 40 of 51 P-gp- patients achieved CR (33% v 78%; P = 10(-4). The prognostic value of IDA and P-gp expression was confirmed in multivariate analysis. These data suggest that the determination of IDA and P-gp expression may be useful in designing therapy for patients with AML.
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PMID:Predictive value for treatment outcome in acute myeloid leukemia of cellular daunorubicin accumulation and P-glycoprotein expression simultaneously determined by flow cytometry. 753 92

Although it has been shown that the percentage of bone marrow blasts in myelodysplastic syndrome (MDS) constitute the only independent determinant of survival and progression to acute leukemia, the great variability in survival among patients with MDS of similar percentage of blasts has prompted us to investigate new objective, independent prognostic parameters for the selection of high-risk patients. It was suggested that CD34 antigen expression adversely affected the prognosis of acute myelogenous leukemia. However, no study has been published so far on clinical and prognostic significance of CD34 antigen expression in MDS. Bone marrow biopsies from 58 patients diagnosed as primary MDS were studied using QBEND/10, a monoclonal antibody which recognized the human progenitor CD34 antigen on routine aldehyde-fixed, paraffin-embedded samples. The high percentage of CD34-positive cells (above 3% of total bone marrow nucleated cells) was predominantly observed in cases with RAEB-T, CMML, and to a lesser degree in RAEB. But neither age, hemograms, bone marrow findings including percentage of blasts, ALIP, nor leukemic transformation correlated with the percentage of CD34-positive cells. The median actuarial survival time in the high positive group was significantly shorter (12.0 months) than that of the low group (30.0 months; p = 0.028). The high CD34 aggregate (> or = 3) was selectively found in cases with RAEB, RAEB-T, and CMML. The percentage of bone marrow blasts (p = 0.007) and ALIP (p = 0.030) significantly correlated with number of CD34 aggregates.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:CD34 immunohistochemical staining of bone marrow biopsies in myelodysplastic syndromes. 753 31

The c-mpl proto-oncogene which encodes a member of the hematopoietic cytokine receptor superfamily has been recently shown to be the receptor for thrombopoietin (TPO), which stimulates megakaryocyte progenitor expansion and differentiation. We studied c-mpl expression by Northern blot analysis, in a large series of 58 MDS. No expression was found in 14 patients with refractory anemia (RA) or with refractory anemia with ring sideroblasts (RARS). In contrast 11/26 (42%) patients with refractory anemia with excess of blasts (RAEB), or with RAEB in transformation (RAEBt), and 8/18 (44%) patients with chronic myelomonocytic leukemia (CMML) expressed c-mpl. In CMML patients, no correlation was found between c-mpl expression and any prognostic factor tested, nor with the course of the disease. In contrast, in RAEB and RAEBt, expression of c-mpl was correlated with high Bournemouth scoring (P < 0.005) and poor survival (P = 0.02) due to leukemic transformation. Forty-five per cent (5/11) of the c-mpl positive patients evolved towards AML with a mean follow-up of 10.5 months, while 13% (2/15) of the c-mpl negative patients developed a secondary leukemia, with a mean follow-up of 21.1 months. Moreover, in RAEB and RAEBt, a significant correlation was observed between c-mpl, CD34, megakaryocyte glycoprotein IIb (GPIIb) expression, and the presence of dysmegakaryopoiesis. These results indicate that patients with RAEB and RAEBt, with high expression of the c-mpl, CD34, and GPIIb genes, may identify a subgroup of patients with particularly poor prognosis, due to an increased risk of secondary leukemia. More aggressive therapy could be justified in these patients.
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PMID:Prognostic value of c-mpl expression in myelodysplastic syndromes. 753 13

Myelodysplastic syndromes (MDS) form a heterogeneous group of clonal hematopoietic disorders with unfavourable prognosis. Allogeneic bone marrow transplantation is the only potentially curative treatment, but remains limited to a small subgroup of younger patients with HLA-compatible donors. As autologous stem cell transplantation is currently being explored as an alternative treatment strategy for MDS, more information needs to be acquired regarding the clonal nature of the progenitor cells in these autografts. Therefore, we have analyzed the clonal patterns of highly purified hematopoietic progenitors and their mature daughter cells in mobilized peripheral blood collections produced from five female patients with high-risk MDS in complete hematologic remission. X-chromosome activation patterns of flow-sorted immature (CD34 + 38low, CD34 + 33low) and committed (CD34 + 38high, CD34 + 33high) progenitors were studied with the polymerase chain reaction-based HUMARA assay. In four patients, a polyclonal remission was shown in all stem cell subpopulations and their mature daughter cells whereas one patient was found to remain skewed in all fractions, except T lymphocytes. This study provides strong evidence that polyclonal immature hematopoietic progenitors can be mobilized and harvested in patients high-risk MDS after treatment with high-dose chemotherapy.
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PMID:Polyclonal primitive hematopoietic progenitors can be detected in mobilized peripheral blood from patients with high-risk myelodysplastic syndromes. 757 31


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