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)

The prognostic value of CD34 expression on leukaemic blast cells was assessed in 38 patients with acute myeloid leukaemia. Nineteen patients had more than 10% CD34 positive blast cells. Median survival for the CD34 positive patients was 125 days and for the CD34 negative patients the median survival has not yet been reached at day 575 (p = 0.06). Of those patients who received intensive chemotherapy, CD34 positive patients (n = 13) had a median survival of 150 days while for CD34 negative patients (n = 14) the median survival has not yet been reached (p = 0.01). Adjustment for age and pre-existing myelodysplastic syndrome did not affect the correlation of CD34 positivity with survival (p = 0.02). Over the period of observation (median 10 months, range 2-19 months) the relative risk of death was 5 times greater for the CD34 positive patients. This study suggests that CD34 expression is an adverse prognostic marker, independent of age and pre-existing myelodysplasia.
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PMID:The prognostic significance of the CD34 antigen in acute myeloid leukaemia. 128 45

To evaluate the clinical value of the expression of multidrug resistance P-glycoprotein (P-170) on the surface of acute nonlymphoblastic leukemia (ANLL) cells, we analyzed specimens from 150 newly diagnosed patients for staining with MRK16, a monoclonal antibody (MoAb) that binds to an external epitope of P-170. Other surface markers (CD13, CD14, CD15, and CD34) were studied by the same technique. A marker was considered positive when 20% or more cells were stained. Of 150 samples, 71 were P-170-positive. These cases did not differ from P-170-negative cases with regard to age, sex, initial white blood cell (WBC) counts, or French-American-British (FAB) type (except for M3 ANLL, which were more frequently negative). However, leukemias arising from previous myelodysplastic syndrome (MDS) and therapy-induced leukemias were more frequently P-170-positive. CD34 and P-170 expression were significantly associated. All patients were treated by intensive chemotherapy. Complete remission (CR) rates were significantly lower in P-170-positive (23/71, 32%) than in P-170-negative cases (64/79, 81%) (P less than 10(-5)). CD34 positivity was also associated with a low remission rate (P less than 10(-5)). Survival was shorter for P-170- and CD34-positive patients (P less than 10(-5)). The prognostic value of both markers was confirmed in multivariate analysis. CR duration was also shorter for P-170-positive cases, but the difference is less significant (P = .05). It is concluded that P-170 analysis may be an important tool for predicting the outcome of intensive chemotherapy in ANLL patients.
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PMID:Clinical significance of multidrug resistance P-glycoprotein expression on acute nonlymphoblastic leukemia cells at diagnosis. 162 8

As part of an epidemiological survey of myelodysplastic syndromes (MDS) in southern Tasmania, 62 MDS patients identified over a 2 year period were tested for the presence of CD34, the human progenitor cell antigen (HPCA), in their peripheral blood. The results were correlated with transformation to acute myeloid leukemia (AML) and patient survival, and CD34+ status was compared as a prognostic indicator with Bournemouth score, cytogenetics, and CFU-GM colony growth which were also assessed. Circulating CD34+ cells were found in 23 of the 62 MDS patients; 9 of the 23 patients with circulating CD34+ cells transformed to AML, as compared with none of the 39 CD34 negative patients (P less than 0.0001); and 11 of the 23 patients with circulating CD34+ cells were dead at the end of the 2 year period, as opposed to 6 of the 39 with no CD34+ cells (P less than 0.03). The Bournemouth score was also significantly associated with transformation to AML (P less than 0.0001) and poor survival (P less than 0.04). These were the only significant associations of the possible prognostic factors studied with either transformation or survival. In summary, the presence of circulating CD34+ cells was significantly associated with both progression to AML and poor survival and was found to be a better prognostic indicator than cytogenetics or CFU-GM colony growth.
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PMID:Circulating CD34+ cells: an adverse prognostic factor in the myelodysplastic syndromes. 137 68

In order to analyze the correlation between environmental exposure and the clinicopathological picture in acute myeloid leukemia (AML), cytogenetic, cyto-immunologic and clinical studies were performed in 70 newly diagnosed AML patients, 30 of which were anamnestically exposed to pesticides (21 cases) or to organic solvents (9 cases). Clonal chromosome aberrations, with involvement of chromosome 5 and/or 7 were more frequently encountered among exposed patients. While the classical t(15;17), t(8;21) and t(9;11) were detected more frequently among non-exposed patients, other recurring chromosome changes in the exposed group were: rearrangements leading to total or partial monosomy 17p (5 cases), structural aberrations involving the band 16q22 (4 cases), trisomy 11q (2 cases), breaks involving bands 6p23, 7p14, 11q13 (2 cases each). Cytologically, trilineage myelodysplasia was observed in 21 exposed patients, whereas morphologic aberrations of the non-blast cell population were confined to a minority of cells in most patients non-exposed. Immunologic studies revealed positivity for the CD34 stem cell marker in 80% exposed patients vs 22% in the non-exposed group. Conventional chemotherapy achieved complete remission in 3/21 patients exposed and in 16/32 patients non-exposed. Median survival was 2 months in the former group and 9 months in the latter group. These findings show that AML following occupational exposure to pesticides and organic solvents may represent a distinct cytogenetic and clinicopathological entity.
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PMID:Morphologic, immunologic and cytogenetic studies in acute myeloid leukemia following occupational exposure to pesticides and organic solvents. 152 67

Clonality of myeloid and lymphoid cell fractions obtained from peripheral blood (PB) or bone marrow (BM) of five patients with a myelodysplastic syndrome (MDS), was studied by combined immunophenotypic analysis and DNA in situ hybridization. This novel technique enables quantitative and direct analysis of cytogenetic alterations in nondividing cells of distinct cell lineages. Four patients with a trisomy 8 and one patient with a translocation (1;7) were studied. For cell lineage determination, antibodies specific for progenitor cells (CD34), myeloid cells (CD15), monocytes (63D3), T cells (CD3), and B cells (CD19,20,22) were used. In one patient with a trisomy 8, BM cells were available and the erythroid lineage could be studied. For detection of cytogenetic aberrations, we used chromosome-specific repetitive DNA probes. In three patients, all nonlymphoid cells carried the cytogenetic abnormality; in two patients, mosaicism within these lineages was suggested by the relative low numbers (35% to 55%) of aberrant cells. None of the T or B cells of the five patients carried the chromosomal aberrations. We conclude that combined immunophenotyping and in situ hybridization is a feasible technique to study lineage involvement. Our data suggest that the chromosomal aberrations studied in MDS are restricted to the myeloid lineages.
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PMID:Combined immunophenotyping and DNA in situ hybridization to study lineage involvement in patients with myelodysplastic syndromes. 155 74

Previous studies have indicated relative resistance to chemotherapy in the myelodysplastic syndromes (MDS) and associated acute leukaemia. To determine if multidrug resistance may contribute to chemoresistance in these disorders, we studied bone marrow specimens for P-glycoprotein expression (P-GP) by immunocytochemical staining with monoclonal antibodies reactive with cytoplasmic (C219) or surface epitopes (MRK16) of P-GP. Forty-five case specimens from 43 patients were studied, including 32 cases of primary MDS, seven cases of acute myeloid leukaemia (AML) following MDS, and six therapy-related haematological disorders. Cytogenetic analysis was available on 36 specimens. Two staining patterns were detected: (1) cytoplasm and plasma membrane, and (2) staining restricted primarily to the nuclear-cytoplasmic junction. P-GP was detected in seven (22%) cases of primary MDS, four (57%) cases of AML evolving from MDS, and five (83%) cases of therapy-related haematological disorders. Expression of P-GP was restricted to blasts and leukaemic monocytes, and was otherwise absent from terminally differentiated blood cells. Analysis of the relation between P-GP expression and reactivity with the human progenitor cell antigen CD34, revealed a highly significant association (P = 0.001). P-GP reactivity was distributed equally among normal and abnormal karyotypes and did not correlate with specific cytogenetic abnormalities. These findings indicate that multidrug resistance in MDS and karyotypically-related haematological disorders is closely linked to a stem cell phenotype and may contribute to chemoresistance in these disorders.
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PMID:Expression of the multidrug resistance gene product (P-glycoprotein) in myelodysplasia is associated with a stem cell phenotype. 167 16

The effects of four recombinant hemopoietic growth factors (HGF) and of the impure factor HTB9 on proliferation and maturation of marrow myeloid (CFU-GM) and erythroid (BFU-E) progenitor cells were studied in 22 cases of myelodysplastic syndromes (MDS). In most cases, IL-3, GM-CSF and G-CSF increased significantly the number of myeloid colonies, the best combination being IL-3 + GM-CSF. A significant increase in the myeloid colony/cluster ratio was also noted, but cytological examination of colony cells showed little maturation. The analysis of myeloid colony surface markers with four monoclonal antibodies (to CD13, CD15, CD33 and CD34) showed minor modifications with an increase of CD13 and CD15 in about one third of cases when compared to control without HGF. Erythroid colonies were obtained in one case with erythropoietin alone, and in 19 cases with the addition of GM-CSF and/or IL-3. In short-term liquid cultures, IL-3, GM-CSF and G-CSF increased 3H-thymidine incorporation. We conclude that progenitor cells of most MDS are able to proliferate in the presence of HGF, with wide case-to-case variations. However, the pattern of growth remains abnormal when compared to normal marrow. Although the combination of IL-3 and GM-CSF is the most efficient, there is a large overlap in the stimulating effects of all factors studied.
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PMID:In vitro effects of recombinant hemopoietic growth factors on progenitor cells from patients with myelodysplastic syndromes. 170 6

We have established a new nonlymphoid leukemic cell ine from a patient with myelodysplastic syndrome (MDS), which progressed to overt leukemia. The parental cell line and a subline derived from this line have absolute dependency on several cytokines for their long-term survival and growth. The parental line designated F-36P requires granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3) for continuous growth, while a subline designated F-36E can be maintained in the presence of erythropoietin (Epo) alone. When these cytokines are depleted, both the parental and the subline cells die within several days, even in medium supplemented with fetal calf serum (FCS). F-36E, maintained in the presence of Epo, constitutively synthesizes hemoglobin at a significant level. F-36P, which is usually maintained in the presence of GM-CSF or IL-3, can be induced to synthesize hemoglobin when GM-CSF or IL-3 is substituted by Epo. The surface marker profile shows that the F-36P cells are positive for the leukocyte common antigen (CD45) and some common multilineage markers such as CD13, CD33, and CD34, and negative for T- and B-cell antigens and mature myelomonocytic antigens. However, some monoclonal antibodies recognizing erythroid and platelet glycoproteins react with these cells. Thus, this cell line has a multilineage phenotype, suggesting that the transformation event occurred in a multipotent stem cell. It is also evident that the F-36 cells can be induced to differentiate into the erythroid lineage in the presence of Epo. This, to our knowledge, is the first description of a human leukemic cell line that can be stimulated to synthesize hemoglobin by Epo.
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PMID:Establishment and erythroid differentiation of a cytokine-dependent human leukemic cell line F-36: a parental line requiring granulocyte-macrophage colony-stimulating factor or interleukin-3, and a subline requiring erythropoietin. 183 51

Indirect immunofluorescence staining with monoclonal antibody (MoAb) CL203.4 of malignant cells from 269 patients with hematologic malignancies showed a heterogeneous expression of CD54/intercellular adhesion molecule-1 (ICAM-1). This marker was expressed by malignant cells of 57 out of 118 patients with myeloid malignancies and 69 out of 135 with B-lymphoid malignancies. On the other hand, CD54 was not detected on malignant cells of 16 patients with T-lymphoid malignancies. In myeloid malignancies, CD54 is preferentially expressed by "stem cell-derived" malignancies, being detectable on blast cells from almost all patients affected by chronic myelogenous leukemia in blast phase or myelodysplastic syndromes and by only 34% of patients with de novo acute myeloid leukemia (AML). The expression of CD54 did not correlate with any specific myeloid FAB subtype, although three cases of highly undifferentiated AML (FAB MO) displayed maximal levels of the antigen. The expression of CD54 in AML was significantly associated with that of CD34 and HLA-DR antigens. In B-lymphoid malignancies, CD54 expression appears to correlate with the differentiation stage of malignant cells, since B-origin acute lymphoblastic leukemias and conventional B-chronic lymphocytic leukemias (B-CLL; ie, "dim SIg" CLL) expressed lower levels of CD54 than more mature lymphoproliferative disorders ("bright SIg" CLL, prolymphocytic leukemias, and lymphoplasmacytic tumors). "High-grade" B-cell non-Hodgkin's lymphomas (B-NHL) express in general a higher level of CD54 than "low-grade" ones. This finding in conjunction with the expression of CD54 in all 17 patients with "bright SIg" CLL investigated (characterized by marked organomegaly and poor prognosis) suggest that the differential expression of CD54 in lymphoproliferative disorders may also relate to their degree of malignancy.
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PMID:Differential expression of CD54/intercellular adhesion molecule-1 in myeloid leukemias and in lymphoproliferative disorders. 197 71

A study of surface markers and in vitro growth in semi-solid and liquid medium was performed in 35 patients with newly diagnosed myelodysplastic syndrome (MDS). Surface markers were studied by CD34, CD13, CD14, CD15, and CD33 monoclonal antibodies. There was no strict correlation with the FAB typing, but CD34 was expressed only in refractory anemia with excess of blasts (RAEB) or RAEB in transformation (RAEB-t). CD14 was markedly positive in the 4 cases of chronic myelomonocytic leukemia. Colony-forming cells were assessed by culture in semi-solid medium in the presence of HTB9 as growth factor. Four growth patterns were identified: a) normal growth (6 cases); b) no growth or low plating efficiency (10 cases); c) low colony and high cluster number (15 cases); and d) normal or high colony number with high number of clusters (4 cases). Expression of CD34 was associated with low colony and high cluster number. Finally we studied the proliferation and differentiation capacities in liquid culture without stimulating factor. Fifteen patients had a spontaneous proliferation. This was not correlated with any surface marker. Differentiation assessed by the loss of CD34 and/or the increase of CD15 by more than 20% at day 7 was observed in 21 cases. None of the surface markers or growth patterns was associated with a specific chromosomal abnormality, except the lack of growth in liquid culture observed in all 5q deletion cases. In univariate analysis, RAEB and RAEB-t FAB subtypes, percentage of blasts higher than 5%, staining by CD33 and CD34, and lack of differentiation in liquid culture were significantly associated with progression to leukemia and shorter survival. In multivariate analysis, only CD34 expression (P = .002) and percentage of blasts (P = .05) remained independent significant variables. CD34 was the only significant variable for prediction of survival (P = .05). It is concluded that surface marker analysis at diagnosis and after liquid culture may be a useful tool for the initial evaluation of MDS.
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PMID:Myelodysplastic syndromes: a study of surface markers and in vitro growth patterns. 232 1


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