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

The aim of this study was simultaneously to evaluate the potential influence of cytogenetic, immunophenotypic and cell culture studies in the evolution of the myelodysplastic syndromes (MDS) with particular attention to the value of the two latter features in predicting the outcome of those patients in which karyotypic information is normal or not available. A series of 77 newly diagnosed patients with primary MDS were analyzed. Immunophenotypic studies were carried out by flow cytometry in triple color combinations: CD34/CD33/CD38, CD15/CD34/HLADR and HLADR/CD13/CD45. In all, 63% of patients showed a normal karyotype and 37% showed clonal abnormalities. In immunophenotypic analysis, overall 90% of patients displayed phenotypic aberrations and 60% showed two or more aberrations. In univariate analysis, 10 variables had a significant influence on survival: >10% bone marrow (BM) blast cells, >or=peripheral blood (PB) cytopenias, >2% of BM CD34+ cells, >85% of BM myeloid cells, >7% monocytic cells, <49% of neutrophils, a neutrophil/monocytic cell ratio <7, more than three phenotypic aberrations and >80 colony-forming units for granulocytes and macrophages (CFU-GM)/10(5) plated cells. Only the presence of >or=5% of BM blast cells (P=0.001) and cytogenetic subgroups (P=0.008) showed independent prognostic significance by multivariate analysis. In patients lacking cytogenetic information or in which the karyotype was normal additional markers had an independent prognostic value in multivariate analysis: >or=2 phenotypic aberrations (P=0.001) and >or=2 PB cytopenias (P=0.004). In summary, our results show that in patients in whom the karyotype is normal or where an insufficient amount of mitoses is obtained, immunophenotype could help to establish a prognosis.
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PMID:Impact of immunophenotype on prognosis of patients with myelodysplastic syndromes. Its value in patients without karyotypic abnormalities. 1516 9

Cytogenetic abnormalities are observed in approximately one half of cases of myelodysplastic syndrome (MDS). Partial or complete chromosome losses and chromosome gains are frequently found, but there is a relatively high incidence of unbalanced translocations in MDS. We describe here two cases of MDS with an unbalanced translocation, der(11)t(11;12)(q23;q13). Both patients were 69 years of age and diagnosed with refractory anemia with excess of blasts in transformation (RAEB-t) according to the high percentage of blasts in the peripheral blood. Cytoplasmic hypogranulation of neutrophils was evident as a dysplastic change. The blasts were positive for CD4 and CD41a as well as CD13, CD33, CD34 and HLA-DR in both cases. Chromosome analysis showed complex karyotypes including a der(11)t(1;11)(q11;p15)t(11;12)(q23;q13) in case 1 and der(11)t(11;12)(q23;q13) in case 2 plus several marker chromosomes. Spectral karyotyping confirmed the der(11)t(11; 12)(q23;q13) and clarified the origin of marker chromosomes, resulting in del(5q) and del(7q). Fluorescence in situ hybridization (FISH) analyses with a probe for the MLL gene demonstrated that the breakpoints at 11q23 were telomeric to the MLL gene in both cases. FISH also showed that the breakpoint at 11p15 of the case 1 was telomeric to the NUP98 gene. Considering another reported case, our results indicate that the der(11)t(11;12)(q23;q13) is a recurrent cytogenetic abnormality and may be involved in the pathogenesis of advanced-stage MDS.
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PMID:Unbalanced translocation der(11)t(11;12)(q23;q13): a new recurrent cytogenetic aberration in myelodysplastic syndrome with a complex karyotype. 1552 5

The two acute myelomonocytic leukemia sister cell lines MOLM-17 and MOLM-18 and the Epstein-Barr-virus positive non-malignant B-lymphoblastoid cell lines (B-LCLs) B422 and B423 were established from the bone marrow sample of a 60-year-old Japanese male in the advanced leukemic phase of refractory anemia with excess of blasts, a subtype of myelodysplastic syndromes (MDS). MOLM-17/-18 are proliferatively responsive to the growth factors present in the culture supernatant of the 5637 cell line. The B-LCLs are constitutively growth factor-independent. MOLM-17 and B422 were established at eight months after the initial diagnosis, while MOLM-18 and B423 were derived from a sample one month later. Immunophenotyping of the first leukemia sample revealed a mixed lineage leukemia immunophenotype with positivity for terminal deoxynucleotidyl transferase (TdT), CD13 and CD19; the second sample revealed solely myeloid characteristics with positivity for CD13, CD41 and CD61, whereas TdT was negative. MOLM-17/-18 showed immunomarker profiles typical of the myelomonocytic lineage. The karyotype analysis of MOLM-17/-18 revealed various non-random numerical and structural abnormalities including del(5)(q?), -7, der(11)add(11)(p11.2)add(11)(q23), add(17)(p11.2), add(18)(p11.2), -20, -22 as common aberrations. Treatment with tumor necrosis factor-alpha induced pronounced cellular differentiation of both cell lines into macrophage-like cells. The overall profile of MOLM-17/-18 based on their extensive immunological, cytogenetic and functional characterization suggests that these cell lines together with the paired B-LCLs B422 and B423 may represent scientifically significant in vitro models which could facilitate investigations into the pathobiology of MDS.
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PMID:Acute myeloid leukemia cell lines MOLM-17 and MOLM-18 derived from patient with advanced myelodysplastic syndromes. 1586 12

Myelodysplastic syndromes (MDS) are malignant disorders of hematopoietic cells. For many neoplasms, immunophenotype data of the neoplastic cells provide valuable information in clinical practice. However, the clinical values of immunophenotype data have not yet been firmly established for MDS. Since MDS blasts are not predominant in the bone marrow and peripheral blood, which makes reliable immunophenotyping of blasts difficult, we used a newly developed density-centrifugation reagent to generate blast-enriched MDS samples for phenotyping. The key findings of our study, which phenotyped blasts from 116 patients with MDS or acute leukemia transformed from MDS, were the following. (1) MDS blasts were usually CD34( + )CD38( + )HLA-DR( + )CD13( + )CD33( + )CD2(-)CD3(-)CD5(-)CD8(-)CD19(-)CD20(-) in flow cytometric analysis and often lacked myeloperoxidase in cytochemistry, regardless of the MDS subtype. (2) MDS blasts showed asynchronous expression of antigens (expression of both stem cell antigens and antigens of mature myeloid cells). (3) During disease progression of MDS, phenotypic clonal evolution (transition from blasts with a relatively mature phenotype to blasts with a more immature phenotype) occurred in at least some cases. (4) CD7-positivity was an independent variable associated with a short survival in MDS. Further studies of blast immunophenotypes will deepen our understanding of MDS and hopefully improve the clinical approach to these intractable disorders.
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PMID:Clinical implications of blast immunophenotypes in myelodysplastic syndromes. 1610 3

Recent data suggest that myeloid neoplasms are organized hierarchically in terms of self-renewal and maturation of early progenitor cells, similar to normal myelopoiesis. In acute myeloid leukemia (AML), the NOD/SCID mouse-repopulating leukemic stem cells usually co-express CD123 with CD34, but lack CD38. So far, however, little is known about expression of other markers and targets on these progenitors. In the present study, expression of target antigens on CD34+/CD38- cells was analysed by multi-color flow cytometry in patients with AML (n = 18), myelodysplastic syndromes (MDS, n = 6), chronic myeloid leukemia (CML, n = 8) and systemic mastocytosis (SM, n = 9). The IL-3Ralpha chain (CD123) was found to be expressed on CD34+/CD38- cells in a majority of the patients in all disease categories. Independent of the type of disease, the vast majority of these stem cells co-expressed aminopeptidase-N (CD13) and CD44 in all patients. By contrast, the CD34+/CD38- progenitor cells expressed variable amounts of the target receptor CD33, c-kit (CD117) and AC133 (CD133). In conclusion, neoplastic stem cells in various myeloid neoplasms appear to express a similar phenotype including target antigens such as CD13, CD33 and CD44. Since many of these targets are not expressed on all stem cells in all patients, the elimination of the entire clone may require combinations of targeted antibodies or use of additional drugs.
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PMID:Detection of molecular targets on the surface of CD34+/CD38-- stem cells in various myeloid malignancies. 1632 50

To study the effects and possible mechanism of Vitamin K(2) (VK(2)) in the treatment of MDS-JSN04 cells, the changes of morphologic features of MDS-JSN04 cells were investigated by cytomorphology, the apoptosis of MDS-JSN04 cells was observed by transmission electron microscope; cellular proliferation was determined by the MTT assay; cell apoptosis, cell cycle shift and expression of myeloid-specific differentiation antigen (CD11b, CD13) were analyzed by flow cytometry (FCM). The expression of apoptosis-related genes bcl-2, survivin and bax were detected by retrotranscriptase polymerase chain reaction (RT-PCR); the activity of caspase-3 was determined by chemiluminescence assay. The results showed that the typical apoptotic morphological features appeared in cells treated with VK(2) for 72 hours; VK(2) induced apoptosis of MDS-JSN04 cells and in a dose-and-time-dependent manner, G(0)/G(1) cell arrest and significantly down-regulated the expression of bcl-2 and survivin, but had no effect on the expression of bax; the activity of caspase-3 significantly increased. It is concluded that VK(2) induces apoptosis of MDS-JSN04 cells through activating caspase-3 pathways and the apoptosis-related genes bcl-2, survivin may play an important role in this process.
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PMID:[Inhibition effect of vitamin K2 on human MDS-JSN04 cell line and its possible mechanism]. 1640 73

We report a chronic myelomonocytic leukemia (CMML) patient whose initial symptom was pleural effusion, which is extremely rare. A 61-year-old male was referred to our hospital because of leukocytosis with blasts and pleural effusion with chest pain. Bone marrow examination showed trilineage dysplasia with 14% blasts and a normal karyotype. He was diagnosed as having MDS (RAEB) and infectious pleuritis on admission. Despite administration of antibiotics, leukocytosis with monocytosis and pleural effusion progressed rapidly. His diagnosis was then changed to CMML-2 and pleural infiltration due to leukemic cells expressing CD13, CD14 and CD33. After the leukocytosis was brought under control with hydroxycarbamide, the patient's pleural effusion disappeared.
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PMID:[Chronic myelomonocytic leukemia with pleural effusion as the first clinical sign]. 1644 18

This study was aimed at exploring the immunophenotypic features of blasts in patients with myelodysplastic syndromes (MDS). Four-color flow cytometry using conventional and secondary gating strategies was used to immunophenotype blasts and the CD34 positive cells in bone marrow nucleated cells of 29 patients with MDS. The results showed: (1) with progression of MDS from RA/RAS, RAEB to RAEB-T, the proportion of CD34(+) cells were gradually increased from 8.0%, 46.4% to 76.8% (P < 0.05); (2) using CD45 vs SSC gating strategy, with the transformation of RA/RAS, RAEB to RAEB-T, the expression of HLA-DR, CD13, CD33, CD117 were also gradually increased (P < 0.05), and the expression of CD15 was gradually decreased (P < 0.05); (3) using CD45 vs CD34 gating strategy, the expression of HLA-DR, CD13, CD33, CD117 on blasts were higher by secondary gating method than those by conventional gating (P < 0.05). However, there were no significant difference (P > 0.05) in the expression of above-mentioned antigens on CD34(+) cells among different MDS subtypes. It is concluded that conventional gating method can reflect MDS progression from RA/RAS, RAEB to RAEB-T, and secondary gating strategy may accurately reflect the biological features of blasts in MDS. Abnormal expression of CD34 is related to the immaturity level and heterogeneity of blast cells, which is beneficial to the diagnosis of clinically suspected MDS incapable of diagnosing with morphology and cytogenetics.
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PMID:[Four-color flow cytometric immunophenotypic features of blasts in myelodysplastic syndromes]. 1658 91

We used a new method of data presentation and analysis, termed antigen mapping, to characterize recurring myeloblast phenotypic abnormalities in a series of 28 cases of myelodysplastic syndrome (MDS), including refractory anemia with ringed sideroblasts (RARS), refractory anemia with multilineage dysplasia (RCMLD), and refractory anemia with excess blasts (RAEB). Abnormal patterns of CD34 and CD117 expression were present in 50% of RARS, 68% of RCMLD, and 100% of RAEB cases. The presence of decreased myeloblast CD45 density, increased CD13 and CD34 density, and increased expression of CD11c and CD4(dim) were MDS grade-related. There was a direct relationship between the number of myeloblast phenotypic abnormalities (phenotypic score) and MDS grade. The myeloblast phenotypic scores also were correlated highly with International Prognostic Scoring System scores and risk categories. We found the antigen mapping technique to be an efficient data presentation and analysis method for the detection of MDS-associated abnormalities of antigen distribution and density.
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PMID:Myeloblast phenotypic changes in myelodysplasia. CD34 and CD117 expression abnormalities are common. 1669 Apr 88

The diagnosis of myelodysplastic syndromes (MDS) is based on peripheral cytopenias, bone marrow (BM) morphology and karyotyping. This may be difficult in cases with few dysplastic elements in BM and a normal karyotype. We examined the utility of flow cytometric analysis for the differential diagnosis between MDS and non-clonal disorders (NCD) presenting peripheral cytopenias. Quantitative assessment of CD45, CD16, CD13, CD11b, CD10 and CD64 in granulocytes and monocytes, and CD71 and glycophorin A in erythroblasts besides CD34+ cell count was performed in BM of 31 consecutive newly diagnosed patients with MDS, 11 patients with NCD and 11 healthy controls (BM donors). In MDS, the median number of phenotypic abnormalities found was 3 (1-8). The WPSS score showed a correlation with the total number of changes per case (r=0.48; p=0.002). Decreased SSC in promyelocytes correlated with the peripheral neutrophil count (r=-0.46; p=0.007). In NCD, the normal variation of antigen expression along granulocytic and erythroblast maturation was always maintained. In the discriminant analysis, SSC of CD34+ cells, together with that of promyelocytes and metamyelocytes were able to correctly classify 87% of the cases as clonal or non-clonal. Our quantitative approach permitted to detect at least one abnormality in antigen expression in every case of MDS. However, the most important parameters for differential diagnosis with NCD were the analysis of the granularity in immature cells, especially of the granulocytic series.
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PMID:Detection of hematopoietic maturation abnormalities by flow cytometry in myelodysplastic syndromes and its utility for the differential diagnosis with non-clonal disorders. 1675 Aug 52


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