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)

Between 1983-1988 bone marrow samples obtained from 195 peroxidase-negative leukemia patients were analyzed for their surface antigens. Thirteen of these patients (6.7%) had myelomonocytic-positive and lymphoid-negative antigens. These leukemic cells reacted with CD13 in eight patients, CD33 in seven, CD11 in six and CDw41 in two. In none of these patients did the leukemic cells react with CD1, CD2, CD3, CD4, CD5, CD8, CD10, CD19 or CD20. Leukemic cells from two patients were reactive with CD7. These leukemic cells demonstrated L2 morphology in 11 patients and L1 morphology in one patient. The leukemic cells from the final patient were diagnosed as those of leukemic transformation of myelodysplastic syndrome. Chromosomal abnormality was observed in approximately half of the patients examined (6/10). Cytochemical analysis revealed that the leukemic cells were negative for periodic acid Schiff stain but positive for acid phosphatase. The prognosis of these patients was markedly poor as compared to acute lymphocytic leukemia or typical peroxidase-positive nonlymphocytic leukemia. Complete remission was induced in only 30% of patients and duration of survival was short (4.7 months). This suggests that myelomonocytic antigen-positive peroxidase-negative acute leukemia is a distinct type of leukemia and may require more aggressive therapy to improve survival.
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PMID:Peroxidase-negative and myelomonocytic antigen-positive acute leukemia. 132 47

Conflicting results have been published on whether or not myelodysplastic syndromes (MDS) affect all cell lineages. Involvement of myeloid and erythroid cell lineages has been regularly observed, but it remains controversial whether the different lymphoid cell lineages are involved. In this study of eight patients with MDS associated with monosomy 7, fluorescent in situ hybridization (FISH) was used to enumerate the chromosomes 7 in interphase cells. With the probe D7Z1, the rate of false-positive detection of monosomy 7 was 3% +/- 2% in normal cells. T- and B-cell lines were established from eight patients with MDS and monosomy 7. As determined by FISH in interphase cells, 1.9% (0% to 3%) of the cells in the B-cell lines showed one fluorescent spot and 1.1% (0% to 2.9%) of the cells in the T-cell lines. These values do not differ from normal values. However, the possibility that normal cells were selected when the T- and B-cell lines were established could not be excluded. Therefore, peripheral blood cells were obtained, separated according to surface markers specific for lymphoid and myeloid cell lineage with a cell sorter, and analyzed for the expression of monosomy 7 by FISH. Antibodies recognizing T cells (CD3), B cells (CD20), natural killer (NK) cells (CD57), monocytes and granulocytes (low and high expression of CD11b antigen), and myeloid progenitors (CD33) were used to separate cells. The expression of monosomy 7 in the T cells, NK cells, and B cells did not differ from control values. These results in the lymphoid subpopulations are in stark contrast with the observations in the myeloid populations; the percentage of cells with monosomy 7 ranged from 9% to 78% (controls: 6% +/- 2%) in cells with low CD11b expression, 20% to 89% in cells with a high expression of the CD11b antigen (controls: 7% +/- 3%), and 23% to 91% in the CD33 positive cells (controls: 5% +/- 3%). The results of this study suggest that monosomy 7 does not usually affect lymphoid subpopulations but is restricted to committed progenitor cells with the capacity to differentiate into mature myeloid cells.
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PMID:Clonal analysis of myelodysplastic syndrome: monosomy 7 is expressed in the myeloid lineage, but not in the lymphoid lineage as detected by fluorescent in situ hybridization. 161 Oct 87

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

A five-year-old boy initially diagnosed common ALL was developed to acute myelomonocytic leukemia. At onset, the bone marrow was hypercellular and 77% of the cells were blasts, mainly lymphoblast-like cells and cytogenetic study demonstrated 45, XY, -7 in all blasts. Cytochemically most of those blasts were negative for peroxidase, sudan black B, alpha-NB esterase staining. The immunological phenotype was J5 (CD10)+, I2 (HLA-DR)+, SmIg-, CyIgmu-, Leu1 (CD5)-, OKT11 (CD2)-, MY7 (CD13)-, suggesting common ALL. Eight months later, the bone marrow cells were occupied with large sized blasts which were almost positive for peroxidase stain and the cells showed coexpression of Mo1 (CD11b)+, MY4 (CD14)+, MY7+, MY9 (CD33)+, MCS2 (CD13)+, I2+, J5-, B4 (CD19)-, Mo2 (CDw14)-, at relapse. He died 2 years and 6 months after his initial diagnosis. An autopsy was performed which revealed generalized infiltration of leukemic cells and aspergillosis of the lung. In general, monosomy 7 is associated with myelodysplastic syndrome in childhood, and is terminated to acute myeloblastic leukemia. In this case, bone marrow blasts demonstrated monosomy 7 cytogenetically, and this case was considered as an acute mixed lineage leukemia of bilineal type. And this case proved that a monosomy 7 can also be terminated to acute mixed lineage leukemia with both lymphoid and myeloid phenotypes.
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PMID:[An autopsy case of acute mixed lineage leukemia with monosomy 7 in a child]. 194 26

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

Based on a 6 1/2-year study of bone marrows (BM) from 74 consecutive adult patients with newly diagnosed primary myelodysplastic syndromes (MDS), we have evaluated the role of immunophenotyping (IP) for subclassification purposes with a selected panel of monoclonal antibodies (Mab). Compared to normal BM IP revealed increased numbers of Mab-defined immature myeloid cells (defined by Mab MY7 [CD13] and MY9 [CD33] (P less than 0.05). Furthermore, decreased numbers of mature myeloid cells (defined by Mab NAT-9 II:3F-6F [NAT-9]) (P less than 0.001) were demonstrated in all French-American-British (FAB) subtypes except refractory anaemia with sideroblasts (RA-S). Since expression of CD13 and CD33 antigens on immature myeloid cells is variable, IP based on a single Mab was often found to be non-informative. However, the construction of myeloid antibody ratios (MAR), designed to give higher figures with increasing numbers of immature myeloid cells and/or decreasing numbers of mature myeloid cells in the BM, disclosed increasing mean ratio values with progressing FAB subtypes. More significant however, was that different prognostic subgroups based on the MAR could be identified independently of the FAB classification. We conclude that the use of IP--especially when MAR is included--is useful in prognostic scoring systems in MDS.
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PMID:Monoclonal antibody ratios in malignant myeloid diseases: diagnostic and prognostic use in myelodysplastic syndromes. 233 36

Cancer and Leukemia Group B demonstrated that adults with acute lymphoid leukemia (ALL) possessing blast cells with myeloid antigens (My+ALL), as identified by monoclonal antibodies against CD13 and CD33, have a worse prognosis than those lacking myeloid antigens (My-ALL). Consequently, we further studied this group of adults with ALL to determine if these immunological groups could be distinguished by morphological and cytochemical criteria. Bone marrow films were classified according to French-American-British Co-operative Group Criteria, assessed for myelodysplasia, and examined for blasts with azurophilic granules. More cases of My+ALL had L2 morphology than did My-ALL (68% vs. 49%, p = 0.04), and more cases of My+ALL were positive for acid alpha-naphthyl acetate esterase (61% vs. 31%, p = 0.03). The presence of myelodysplastic changes was not significantly different in My+ALL (13%) as compared to My-ALL (5%), but more cases of My+ALL had unusual blasts (monocytoid features and cytoplasmic buds) than did My-ALL (19% vs. 0%, p less than 0.01). In addition, more cases of My+ALL had greater than 5% of the blasts with azurophilic granules (42% vs. 13%, p = 0.01). In the My+ALL group the presence of azurophilic granules was associated with a longer median survival (13.5 months vs. 1.5 months, p less than 0.01). We conclude that My+ALL can be suspected when cases possess L2 morphology, unusual blasts, positive staining for acid alpha-naphthyl acetate esterase, and greater than 5% azurophilic granules. In addition, the poor risk group (My+ALL) can be further subdivided into better and poorer risk subgroups based on the presence of azurophilic granules.
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PMID:Morphologic and cytochemical characterization of adult lymphoid leukemias which express myeloid antigen. 316 98

Expression of P-glycoprotein (PGP), the product of the multi-drug resistance mdr1 gene was studied by immunocytochemistry on bone marrow slides using JSB1 monoclonal antibody and the alkaline phosphatase-antialkaline phosphatase (APAAP) and avidin-biotin-peroxidase (ABC) techniques in 82 cases of untreated myelodysplastic syndromes (MDS), of whom ten had evolved to AML (MDS-AML). The relationship between PGP expression, myeloperoxidase activity and immunophenotype of blast cells, karyotype and outcome was also analyzed. PGP expression was found in the blasts of 34 of the 82 patients (41%), the majority of blasts being stained in positive cases. PGP positivity was rare in 'low risk' MDS (RA and RARS: 2/12 cases) as opposed to 'high risk' MDS (RAEB, RAEB-T, CMML: 25/60 cases) and MDS-AML (7/10 cases) (p = 0.04). PGP expression was positively correlated to the presence of myeloperoxidase activity in less than 3% of blasts (p = 0.025), and CD34 antigen expression (p = 0.04), whereas CD33 antigen expression had borderline significance (p = 0.07), demonstrating that PGP expression predominated in blasts with an immature phenotype. An abnormal karyotype, and especially the presence of monosomy 7, was not correlated to a higher incidence of PGP expression, however. There was a trend for more frequent progression to AML and for shorter survival in PGP-positive cases, but differences with PGP-negative cases were not significant. Twenty patients received intensive anthracycline-Ara-C chemotherapy and ten (50%) achieved complete response, including 9/13 (69%) PGP-negative cases and 1/7 (14%) PGP-positive cases (p = 0.03). Twenty other patients were treated with low-dose Ara-C and ten (50%) responded (complete or partial response). PGP-positivity did not negatively affect response to low-dose Ara-C: 4/11 responses in PGP-negative, and 6/9 responses in PGP-positive patients (p = 0.18). Because the treatment choice in advanced MDS (especially between anthracycline-Ara-C or low-dose Ara-C, chemotherapy) is difficult, our preliminary therapeutic results suggest that the analysis of PGP expression could have practical importance in MDS. These findings however, will have to be confirmed on larger numbers of patients. Clinical trials using drugs potentially reverting mdr, activity could also be warranted in MDS.
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PMID:Expression of the multidrug resistance P-glycoprotein and its relationship to hematological characteristics and response to treatment in myelodysplastic syndromes. 751 32

In a search for a mechanism to explain the impaired growth of progenitor cells in patients with myelodysplastic syndromes (MDS), marrow CD34+ cells were purified up to 94.9% +/- 4.2% for normal individuals and 88.1% +/- 17.6% for MDS patients, using monoclonal antibodies and immunomagnetic microspheres (MDS CD34+ cells). Phenotypic subpopulations of these CD34+ cells were analyzed for CD38, HLA-DR, CD33, CD13, CD14, CD41 and CD3 plus CD19, in association with proliferative and differentiative capacities. The 15 studies performed included 12 MDS patients. Coexpression rate of CD13 significantly increased in the MDS CD34+ cell population with a value of 91.4% +/- 11.6% and ranging from 60.3% to 100%, and exceeded 99% in four studies, whereas that of normal CD34+ cells was 49.9% +/- 15.8%, ranging from 28.2% to 70.1% (P < .001). Coexpression rate of CD38, HLA-DR, CD33, CD14, and CD3 plus CD19 in MDS CD34+ cells did not significantly differ from that of normal CD34+ cells. The total number of colonies and clusters grown from 100 normal marrow CD34+ cells was 40.4 +/- 8.6, the range being from 27.2 to 50.3; this varied in MDS marrow CD34+ cells with a value of 34.0 +/- 28.7, the range being 0 to 95.9. The lineage of colonies and clusters promoted by MDS marrow CD34+ cells was predominantly committed to nonerythroid with impaired differentiation in 13 of 15 studies (87%). CD13 is first expressed during hematopoiesis by colony-forming unit granulocyte-macrophage and is absent in erythroid progenitors. Therefore, this study provides direct evidence for the lineage commitment of MDS CD34+ cells to nonerythroid with impaired differentiation and explains the mechanism of nil or low colony expression of MDS progenitor cells to erythroid lineage.
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PMID:Proliferation and differentiation of myelodysplastic CD34+ cells: phenotypic subpopulations of marrow CD34+ cells. 752 67


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