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

We describe two new human leukemia cell lines, MOLM-13 and MOLM-14, established from the peripheral blood of a patient at relapse of acute monocytic leukemia, FAB M5a, which had evolved from myelodysplastic syndrome (MDS). Both cell lines express monocyte-specific esterase (MSE) and MLL-AF9 fusion mRNA. Gene fusion is associated with a minute chromosomal insertion, ins(11;9)(q23;p22p23). MOLM-13 and MOLM-14 are the first cell lines with, and represent the third reported case of, MLL gene rearrangement arising via chromosomal insertion. Both cell lines carry trisomy 8 which was also present during the MDS phase, as well as the most frequent trisomies associated with t(9;11), ie, +6, +13, +19 variously present in different subclones. Despite having these features in common, differences in antigen expression were noted between the two cell lines: that of MOLM-13 being CD34+, CD13-, CD14-, CD15+, CD33+; whereas MOLM-14 was CD4+, CD13+, CD14+, CD15+, CD33+. Differentiation to macrophage-like morphology could be induced in both cell lines after stimulation with INF-gamma alone, or in combination with TNF-alpha, which treatment also induced or upregulated, expression of certain myelomonocyte-associated antigens, including CD13, CD14, CD15, CD64, CD65 and CD87. Together, these data confirm that both cell lines are likely to be novel in vitro models for studying monocytic differentiation and leukemogenesis.
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PMID:Two acute monocytic leukemia (AML-M5a) cell lines (MOLM-13 and MOLM-14) with interclonal phenotypic heterogeneity showing MLL-AF9 fusion resulting from an occult chromosome insertion, ins(11;9)(q23;p22p23). 930

Mononuclear cells of the bone marrow (BM) of patients in various subgroups of the myelodysplastic syndrome (MDS) were studied by flow cytometry for the expression of myeloid and lymphoid markers both on the surface and in the cytoplasm. A significantly higher percentage of the BM cells of MDS patients reacted with monoclonal antibodies (mAbs) to myeloid antigens (CD13, CD15 and CD33) by cytoplasmic staining as compared with cell surface staining. The percentage of BM cells expressing CD34 was markedly elevated in patients with RAEB-T. A distinct finding in MDS patients was the expression of myeloid antigens on mononuclear BM cells. The proportion of individuals whose mononuclear BM cells were positive for surface reactivity with anti-CD13 and anti-CD33 mAbs was highest among RAEB-T patients while none of the patients with RA expressed these surface antigens. Cytoplasmic staining significantly increased the percentage of CD13+ and CD33+ BM cells among RAEB and RAEB-T patients. The proportion of individuals whose BM cells possessed myeloid antigens was increased by cytoplasmic staining in all subgroups of MDS. The BM of a considerable proportion of RAEB-T and RAEB patients showed cells which coexpressed the CD7 and CD3 lymphoid markers along with the CD13 and CD33 myeloid antigens. The present study indicates the importance of comparative surface and cytoplasmic immunophenotyping with CD13 and CD33 mAbs for the diagnosis of subgroups of MDS. The coexpression of CD3 and CD7 with markers of the myeloid lineage may reflect derangement of the differentiation of pluripotent stem cells characteristic for MDS.
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PMID:Analysis of myeloid and lymphoid markers on the surface and in the cytoplasm of mononuclear bone marrow cells in patients with myelodysplastic syndrome. 981 67

Using a multiparameter flow cytometry assay enumerating cells positive for CD13, CD14 and CD66 antigens, we determined the asynchronous CD14/CD66 co-expression in unselected bone marrow and peripheral blood samples with suspected malignant blood disorders. CD14/CD66 co-expression > or = 5% were found in 131/691 bone marrow samples. Only 55 of these exhibited an identifiable population in 2-parameter flow cytometry histograms. Of the 55 samples 43 (78%) came from patients with myeloid disorders; e.g. 11 with myelodysplastic syndromes, 15 with chronic myeloproliferative disorders and 17 with acute myeloid leukaemia. Only one of these 17 cases was a de novo case, while 8 were secondary to another malignant haematological disease and 8 were from the period after cytoreductive therapy. Notably, CD14/CD66 co-expression patterns were related to disease categories; e.g. in chronic myelomonocytic leukaemia and acute myeloid leukaemia following a dysplastic phase the co-expression displayed two subsets in peripheral blood, low-avidity CD14 and low-avidity CD66, respectively. The latter disease category also exhibited these 2 subsets in bone marrow. In all other cases, the CD14/CD66 co-expression in bone marrow was heterogeneous. In conclusion, abnormal CD14/CD66 co-expression might be a valuable parameter in defining asynchronous myelopoiesis in malignant myeloid disorders, especially myeloproliferative disorders and secondary acute myeloid leukemias.
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PMID:Flow cytometric identification of myeloid disorders by asynchronous expression of the CD14 and CD66 antigens. 985 50

The c-kit proto-oncogene encodes a 145 kd tyrosine kinase transmembrane receptor, which plays a key role in haemopoiesis. The c-kit has been classified as CD117 and is especially useful in the differential diagnosis of acute myelogenous leukemia (AML) and acute lymphoblastic leukemia (ALL). We analysed 104 consecutive cases (55 AML, 23 B-cell lineage ALL, three T-cell ALL, 11 blast crisis of chronic myeloproliferative disorders and 12 cases of myelodysplastic syndromes with more than 10% of blasts) referred to our Hospital for immunophenotypic diagnosis and compared the expression pattern of CD13, CD33 and CD117 using the same fluorochrome (phycoerythrin-PE). The recommendations of the EGIL group were followed in order to establish lineage involvement of the blastic population. The threshold used to assign positivity for CD117 was 10%. Bcr/abl, TEL/AML-1 and MLL rearrangements were assessed by molecular methods. CD117 expression was detected in 91% of AML and MDS. All the negative cases corresponded to acute monocytic leukemias. The calculated specificity for myeloid involvement was 0.86 for CD117, 0.36 for CD13 and 0.44 for CD33 (P < 0.005). CD117 was also positive in four cases of ALL. None of these cases showed bcr/abl or MLL rearrangements. In the light of these findings, CD117 expression should yield a higher score, at least one point, in the system currently applied for the diagnosis of biphenotypic acute leukemias (BAL) as its myeloid specificity is greater than that of CD13 and CD33. Moreover, its absence in AML could identify two subgroups of M5b cases. The coexpression of CD117 with cytoplasmic CD79a is often associated with CD7 reactivity, suggesting a stem cell disorder. CD117 should be included on a routine basis for the immunophenotypic diagnosis of acute leukemias.
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PMID:Enhanced myeloid specificity of CD117 compared with CD13 and CD33. 1022 19

We have established a T lymphoid cell line, K2-MDS, from the peripheral blood mononuclear cells (PBMC) of a patient with acute myeloblastic leukemia (AML) transformed myelodysplastic syndrome (MDS). K2-MDS cells are positive for the expression of CD4, CD5, CD13, CD25, CD71, CD95, HLA-DR and cytoplasmic CD3. Southern blotting analysis shows T cell receptor (TCR) beta chain genes rearrangements, whereas immunoglobulin heavy chain (IgH) genes are not rearranged. Further, the patient PBMC contains TCR beta chain genes rearrangements in the same manner as K2-MDS cells. The data indicate that K2-MDS is a T lymphoid cell line derived from a myelodysplastic clone in the patient PBMC. This new MDS-derived cell line K2-MDS may be a useful in vitro model for studies on the pathogenetic mechanisms leading to MDS.
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PMID:Establishment of a myelodysplastic syndrome (MDS)/secondary AML-derived T lymphoid cell line K2-MDS. 1065 44

Refractory anemia (RA) in myelodysplastic syndrome (MDS) without prominent dysplasia closely resemble the mild type of aplastic anemia (AA) in their hematological features. This sometimes makes it difficult to distinguish clearly between the two diseases. Using the multi-color flow cytometric technique, we compared cell surface antigen expression patterns on bone marrow hematopoietic progenitor cells which were isolated as a CD34 positive- CD45 dull positive with low side scatter intensity (CD34(+)CD45(dull+)SSC(low)) population in flow cytogram between RA (n=12) and AA (n=11). The antigens analyzed in CD34(+)CD45(dull+)SSC(low) mononuclear cells were: CD38 and CD71 for cell growth-related antigens, CD 33 and CD13 for myeloid and monocytoid lineage-associated antigens, CD7 and CD19 for lymphoid lineage, and CD14 for a monocytic lineage specific antigen. The percentages of CD34(+)CD45(dull+)SSC(low) cells in bone marrow non-erythroid mononuclear cells, and the expression frequencies of CD38, CD71, CD33 and CD13 antigens in CD34(+)CD45(dull+)SSC(low) progenitors were all significantly decreased in AA compared to normal bone marrows (n=7) (P<0.005). In contrast, in RA bone marrows the percentages of CD34(+)CD45(dull+)SSC(low) cells showed wide distribution and the cell surface antigen expression patterns varied among each case: some cases showed low frequencies of CD38 and CD71 expression as well as AA, whereas the others showed high expression frequency of specific antigen(s) which may reflect the clonal expansion of an abnormal clone in bone marrow. An MDS patient who had progressed from RA to RAEB showed further projecting pattern of expression of CD38 and CD33 in CD34(+)CD45(dull+)SSC(low) population in accordance with the disease progression. These data suggest that analysis of cell surface antigen expression patterns of CD34(+)CD45(dull+)SSC(low) progenitor cells by multi-color flow cytometry appears to be a useful method for qualitative and quantitative assessment of marrow progenitor states in AA and RA, therefore this method could be helpful for early detection of clonal evolution in MDS.
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PMID:Comparative multi-color flow cytometric analysis of cell surface antigens in bone marrow hematopoietic progenitors between refractory anemia and aplastic anemia. 1086 34

Acute monoblastic leukemia (acute myeloid leukemia [AML], French-American-British type M5a) with leukemia cutis developed in a patient 6 weeks after the initiation of erythropoietin (EPO) therapy for refractory anemia with ringed sideroblasts. AML disappeared from both marrow and skin after the discontinuation of EPO. Multiparameter flow cytometric analysis of bone marrow cells demonstrated coexpression of the EPO receptor with CD45 and CD13 on the surface of blasts. The incubation of marrow cells with EPO, compared to without, resulted in 1.3- and 1.6-fold increases, respectively, in tritiated thymidine incorporation and bromodeoxyuridine incorporation into CD13(+) cells. Clinical and laboratory findings were consistent with the EPO-dependent transformation of myelodysplastic syndrome (MDS) to AML. It is concluded that leukemic transformation in patients with MDS treated with EPO may be EPO-dependent and that management should consist of the discontinuation of EPO followed by observation, if clinically feasible.
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PMID:Erythropoietin-dependent transformation of myelodysplastic syndrome to acute monoblastic leukemia. 1171 96

Abnormalities of chromosome 16 other than inv(16)(p13q22), t(16;16)(p13;q22), and del(16)(q22) have not been fully characterized in acute myeloblastic leukemia (AML) and myelodysplastic syndrome (MDS). We report here the first case of AML with del(16)(q11) as a sole abnormality. A 53-year-old woman was initially diagnosed as MDS, refractory anemia with excess of blasts in transformation with normal karyotype. After sixteen months, the disease progressed to overt AML-M1. Myeloblasts were positive for CD13, CD33, and CD34, but negative for HLA-DR. Chromosome analyses of the bone marrow cells showed 46,XX,del(16)(q11) in all metaphase spreads. Multicolor spectral karyotyping also confirmed that del(16)(q11) was not derived from a cryptic translocation, but a simple deletion. Our results, together with three previously reported cases, suggest that del(16)(q11) may be one of the recurrent aberrations in AML and that it could be associated with clonal evolution or disease progression.
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PMID:Deletion of 16q11 is a recurrent cytogenetic aberration in acute myeloblastic leukemia during disease progression. 1173 21

A novel human leukaemia cell line, designated TMD7, was established from blast cells of a patient with de novo acute myeloblastic leukaemia with trilineage myelodysplasia (AML/TLD). As seen in the original blast cells, TMD7 cells expressed CD7, CD13, CD33 and CD34 and showed an abnormal karyotype containing -5, -7, -8, der(16)t(10;16)(q22;q13). The cells proliferated without added growth factors. Growth was stimulated with the addition of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage CSF (GM-CSF) and interleukin 3. Differentiation was not observed with the addition of various cytokines. As a cell line derived from AML/TLD has not been reported, TMD7 will be a useful tool as a model of AML/TLD cells. Recently, it was reported that the Notch system has crucial roles to regulate the self-renewal and differentiation of haematopoietic stem cells. We found that TMD7 cells expressed Notch-1 and Notch-2 mRNA. The exposure to recombinant Delta-1 protein, which was one of the Notch ligands, significantly stimulated the growth of TMD7 cells. This is the first human cell line which was shown to proliferate in response to Delta-1, without artificially expressed Notch protein. Therefore, TMD7 will also be a useful tool to study the mechanism of the Notch-Notch ligand interaction.
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PMID:A novel cell line derived from de novo acute myeloblastic leukaemia with trilineage myelodysplasia which proliferates in response to a Notch ligand, Delta-1 protein. 1197 20

We have established a new hematopoietic cell line from a patient with myelodysplastic syndrome (MDS), which was refractory anemia with excess blasts (RAEB). This cell line, designated TER-3, depends on several cytokines for long-term survival and growth, and requires interleukin-3 (IL-3) for continuous growth. Cytochemical analysis revealed that TER-3 cells are weakly dianisidine positive and nonspecific esterase positive, but peroxidase negative. The surface marker profile shows that the TER-3 cells are strongly positive for myeloid, lymphoid, and megakaryocytic antigens such as CD15, CD19, and CD61, and negative for some common multilineage antigens such as CD13, CD33, and CD34. Thus, this cell line has a multilineage phenotype, suggesting that the transformation event occurred in multipotent stem cells. Dianisidine- and nonspecific esterase-positive TER-3 cells increase with granulocyte-colony stimulating factor (G-CSF) rather than with IL-3. These results suggest that the cell line is useful for understanding the mechanism underlying G-CSF-associated hematopoietic cell differentiation and activation in the patient with MDS.
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PMID:New human myelodysplastic cell line, TER-3: G-CSF specific downregulation of Ca2+/calmodulin-dependent protein kinase IV. 1206 61


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