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)

Four-stem-cell assays, which evaluate megakaryocytic (CFU-Meg), immature and mature erythropoietic (BFU-E, CFU-E), and granulocyte-macrophage (CFU-GM) colony formation, were performed in nine patients with myelodysplastic syndromes (MDS). The CFU-Meg, BFU-E, and CFU-E colony growths were disturbed more often than the CFU-GM colony formation. A CFU-E increase was not recognized in most MDS patients, but a dose-dependent increase of bone marrow CFU-Es in response to erythropoietin (EPO) was recognized only in two refractory anemia (RA) patients whose CFU-Es were more than one tenth of normal controls. One patient with RA and the other with chronic myelomonocytic leukemia (CMML), both of whose bone marrow CFU-Es did not increase at the higher dose of EPO in vitro, were treated with recombinant human EPO (rHuEPO), resulting in no effects. The responsiveness of patients with MDS to various recombinant hemopoietic factors might be predicted by both the residual degree of bone marrow hematopoietic precursor cells and the response of stem cells to the higher doses of each hemopoietic factor.
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PMID:Three-lineage hemopoietic precursor cells and effectiveness of recombinant human erythropoietin in patients with myelodysplastic syndromes. 158 47

Two patients with acute myeloid leukemia (AML) developed a chronic myelomonocytic leukemia (CMMoL)-like state after chemotherapy. Both patients showed morphological evidence of myelodysplasia together with acute leukemia at presentation (Case 1: M5b with trilineage myelodysplasia and Case 2: M4 with dysmegakaryocytopoiesis). They also showed persistent monocytosis without prominent blast cell proliferation after induction therapy. The possibility was suggested that these two patients were in acute transformation from CMMoL at presentation and returned to a CMMoL-like state after induction therapy.
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PMID:Two cases of acute myeloid leukemia evolving into a chronic myelomonocytic leukemia-like state after induction therapy. 160 Feb 70

Myelodysplastic syndromes originate from a pluripotent stem cell. This view, previously suggested by G-6-PD and cytogenetic investigations, has been established unequivocally by X-chromosome inactivation analysis based on DNA polymorphisms and by studies of mutated oncogenes. Two genomic alterations associated with MDS have been analyzed in more detail. Activation of the RAS oncogenes, preferentially N-RAS, is demonstrated in approximately 35% of MDS patients. Mutations in the FMS gene, encoding the CSF-1 receptor, are found in 16% of cases. Interestingly, RAS and FMS mutations are predominantly observed in disorders of myelomonoctic differentiation, i.e., the CMML subtype in MDS and the AML FAB type M4. Moreover, homozygous deletion of the FMS gene may be an important event in the genesis of the MDS variant 5q- syndrome. Preliminary data indicate that defects in tumor-suppressor genes, namely p53, may also contribute to the development of MDS. Different lines of evidence suggest that clinical preleukemia is preceded by a phase in which genetic alterations accumulate without any hematologic change. Cases in point are the detection of RAS and FMS mutations in healthy individuals who had been treated in the past with cytotoxic therapy for lymphoma, the frequent observation of clonal remission in AML patients, or the identification of oncogene mutations in healthy individuals without even a history of malignancy or chemotherapy. Possibly, either germline mutations of oncogenes or tumor-suppressor genes and the process of genomic imprinting may constitute additional factors that predispose hematopoietic stem cells to malignant transformation. Limited as they are, the currently available data suggest that accumulation of genomic lesions, rather than their precise order of development with respect to one another, characterize the multistep process of leukemogenesis in which MDS already represent more advanced stages. The prognostic significance of oncogene mutations in MDS patients is controversially discussed. This issue awaits prospective analyses taking into account the influence of treatment modalities. However, the clinical relevance of molecularly defined parameters has already been established for their use as clonal markers in determining the mode of action and efficiency of different therapeutic approaches.
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PMID:Molecular genetic aspects of myelodysplastic syndromes. 161 6

Serum concentration of interleukin 6 (IL-6) was measured in 45 patients with myelodysplastic syndromes (MDS). A commercially available enzyme-linked immunosorbent assay (ELISA) with a sensitivity of 3 pg/ml was used. While IL-6 was undetectable in healthy volunteers, 32 of the patients with MDS showed IL-6 concentrations higher than 3 pg/ml. In MDS we found serum concentrations of IL-6 between 0 and 150 pg/ml with a median of 9 pg/ml, mean and standard deviation (SD) were 15 and 26 pg/ml respectively. In refractory anemia with excess of blasts in transformation (RAEB-t) the serum IL-6 concentrations were significantly higher than in refractory anemia (RA; p = 0.0025), in refractory anemia with excess of blasts (RAEB; p = 0.0050) and in chronic myelomonocytic leukemia (CMML; 0.0449). No significant difference was detected between RA and RAEB or between CMML and the other types of MDS, while s significant negative correlation was found between the concentrations of IL-6 and hemoglobin (p = 0.0228).
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PMID:Increased serum interleukin 6 levels in patients with myelodysplastic syndromes. 163 76

Forty-three patients with myelodysplastic syndrome (MDS) were retrospectively analyzed for its prognostic factors. We evaluated the relationship of the clinical, biochemical, and hematological data, as well as colony-forming unit myeloid (CFU-C) culture, Bournemouth score, modified Bournemouth score, and modified Dutcher score to the prognosis. The median age was 65 years. Eighteen patients had refractory anemia (RA), 4 had refractory anemia with ringed sideroblasts (RARS), 15 had refractory anemia with excess blasts (RAEB), 2 had refractory anemia with excess blasts in transformation (RAEB-t), and 4 had chronic myelomonocytic leukemia (CMMoL). The median survival of all patients was 482 days. The median survival for each subtype was as follows: RA, 628 days; CMMoL, 350 days; RAEB, 240 days; RAEB-t, 90 days. For RARS, no data have yet been obtained, because only one out of 4 patients with RARS has died. We subdivided all patients into two groups: one group included patients with RA or RARS and the other group included patients with RAEB, RAEB-t or CMMoL. The former group had a median survival of 677 days and the latter group 240 days, p = 0.0035. In the former group, 3 out of 22 patients (13.6%) developed acute myeloid leukemia (AML), as compared to 8 out of 21 patients (38.1%) in the latter group, p = 0.0661. Twenty-five of the 43 patients died: 10 from AML and 15 from infection and/or bleeding.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Myelodysplastic syndrome: a study of prognostic factors. 167 97

More than 1300 MDS cases with clonal cytogenetic abnormalities, 200 of them secondary MDS, have been reported. The most common aberrations in primary MDS are del(5q) (27%), trisomy 8 (19%), monosomy 7 (15%), der(11q) (7%), -5, der(12p) and -Y (5%), del(7q) (4%), and t(1;7), der(3q), del(13q), i(17q) and del(20q) in 2% or less. The 5q- is mostly, but not always, a del(5)(q13q33); it is the cytogenetic hall-mark of the "5q- syndrome" and is frequently found as the sole abnormality. The frequency of the aberrations varies among MDS subgroups: 5q- is most frequent in RA, -5, -7, and der(12p) are more common in CMML and especially in RAEB, and +8 and der(11q) are more often found in RARS. The most common aberrations in secondary MDS are -7 (41%), del(5q) (28%), -5 (11%), der(21q) (9%), 7q-, +8 and der(12p) (8%), t(1;7) and -12 (7%), der(17p) (6%), der(3p) and der(6p) (5%), and der(3q), der(11q), -17, -18 and der(19q) (4%). The average number of abnormalities per case is 5.3, compared with 2.9 in unspecified MDS. The frequency of cytogenetically unrelated clones is 5.7% in secondary and 4.3% in primary MDS. When the literature data are broken down by type of genotoxic exposure, it turns out that -5, -7, and der(17p) are over-represented in patients who have received chemotherapy, whereas 5q- is associated with no exposure or preceding radiotherapy only. The karyotypic profile is prognostically important: patients with -7 or complex karyotypes have a higher risk of progression to acute leukemia and shorter survival.
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PMID:Cytogenetic findings in primary and secondary MDS. 173 69

MDS is primarily a disease of the elderly. Cases who give a history of exposure to X-rays, cytotoxic drugs or leukaemogenic chemicals may be younger. Many cases of MDS present because of an incidental blood count. The most prominent clinical features are those of anaemia, neutropenia, thrombocytopenia. Because haemopoietic tissue is also dysfunctional the pathological effect is often greater than the figures would suggest, even leading to infection of bleeding with normal neutrophil or platelet counts. Occult abscesses are a particular feature. Despite documented abnormalities of the lymphoid system, neither infections characteristic of T-cell immunodeficiency nor autoimmunity is a problem. The proliferation of monocytes in CMML leads to organomegaly, leukaemia cutis, serous effusions and vasculitic lesions caused by the mishandling of circulating immune complexes. Cancer is no commoner than in age-matched controls, but coincident lymphoid tumours do occur. Many patients require long-term blood transfusion and will run into problems of iron overload unless precautions are taken.
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PMID:Clinical features of MDS. 173 80

In an attempt to identify prognostic factors for survival and leukemic transformation, 235 untreated patients with primary myelodysplastic syndromes (MDS) were analyzed in a single center retrospective study. To the well known FAB classification of MDS a supplementary group of patients with pure sideroblastic anemia (PSA) was added, characterized by the absence of dysplastic features of non-erythroid cells. Accordingly, the morphological subtypes were refractory anemia (RA), n = 55; PSA, n = 40; RA with ring sideroblasts (RARS), n = 33; RA with excess of blasts (RAEB), n = 53; RAEB in transformation (RAEB/T) n = 29; and chronic myelomonocytic leukemia (CMML), n = 25. Having screened 28 clinical, cytological, and laboratory parameters by univariate analysis, multiple regression analysis identified six variables with independent prognostic value: percentage of bone marrow blasts, serum LDH activity, PSA, hemoglobin concentration, age, and platelet count. If patients with PSA were excluded, the FAB classification no longer contributed independent prognostic information. Based on the results of this multivariate analysis, a simple scoring system was devised for predicting the survival of patients with MDS. A score of unity was allocated to each of the following parameters: bone marrow blasts greater than or equal to 5%, LDH greater than 200 U/I, hemoglobin less than or equal to 9 g/dl, and platelets less than or equal to 100 x 10(9)/I. As a function of their total score, patients were divided into three risk groups (group A, score 0; group B, score 1-2; group C, score 3-4), which differed significantly in both survival and rates of leukemic transformation. The cumulative survival 2 years after diagnosis was 91% in group A, 52% in group B, and 9% in group C (p less than 0.00005). The actuarial risk of transformation to acute myeloid leukemia at 2 years was 0, 19, and 54%, respectively (p less than 0.05). The inclusion of LDH enzyme levels qualified this scoring system for an accurate assessment of patients with CMML whose prognosis is viewed too favorably when rated by other scores. Furthermore, this score was able to identify those patients with RA and RARS who, without showing an excess of marrow blasts, have an unfavorable prognosis.
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PMID:Primary myelodysplastic syndromes: analysis of prognostic factors in 235 patients and proposals for an improved scoring system. 173 14

1-beta-D-Arabinofuranosylcytosine-5'-stearylphosphate (fosteabine) was administered orally to patients with myelodysplastic syndromes (MDS); refractory anemia with excess of blasts (RAEB), RAEB in transformation, acute leukemia derived from RAEB and chronic myelomonocytic leukemia, in an early phase II study in a multi-institutional study. Among 62 evaluable patients, 2 patients achieved a complete remission, 6 a good response and 8 partial response by daily oral administration of 100-200 mg of fosteabine. The overall response rate was 25.8%. The response rates were almost the same among the four subtypes of MDS. Responses were reached 2-23 weeks (median, 8 weeks) after the start of therapy and continued for 3-50 weeks (median, 10 weeks). Major side effects were myelosuppression and gastrointestinal toxicities. In spite of the disadvantages, such as unpredictable absorption, this newly developed orally administrable cytarabine analogue will be a useful drug in the treatment of MDS.
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PMID:Treatment of myelodysplastic syndromes with orally administered 1-beta-D-arabinofuranosylcytosine-5'-stearylphosphate. 174 80

From 1980 to 1987, three cases of chronic myelomonocytic leukemia (CMML) were encountered among 68 cases of multiple myeloma who survived more than three years from the diagnosis. The incidence (4.8%) of secondary myelodysplastic syndrome (MDS) is almost identical to previous reports, but case reports of chronic myelomonocytic leukemia were rare. In Japan, there are few reports of multiple myeloma patients who later developed secondary MDS or acute myelogenous leukemia (AML). In our cases, none of the 31 patients treated with cyclophosphamide developed secondary MDS, while three of 37 patients treated with melphalan developed CMML. This difference is not statistically significant.
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PMID:Three cases of multiple myeloma developing into melphalan-related chronic myelomonocytic leukemia. 177 Mar 23


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