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)

We studied bone marrow chromosomes in 85 consecutive patients with myelodysplastic syndrome (MDS). Fifty-seven (67%) had a clone with an abnormal karyotype at diagnosis. Eight had secondary MDS, all with abnormal karyotypes. The frequency of abnormal karyotypes in the primary MDS was 64.9%. During subsequent follow-up, five patients acquired chromosome abnormalities; thus, at the end of the study, 72.0% of patients had an abnormal karyotype. The most frequent chromosome abnormalities were 5q-, +8, -7, -5, and -22. Forty patients (i.e., 70% of those with an abnormal karyotype and 47% of the whole group) had one of the karyotype abnormalities associated with secondary MDS or acute nonlymphocytic leukemia; in other words, 5q- or -5, or -7. Of all patients, 21.1% progressed into ANLL. Unfavorable prognostic factors associated with the risk of evolution into ANLL and with shorter overall survival were the presence of greater than 5% of bone marrow blasts, major chromosome abnormalities, and monosomy 7.
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PMID:Chromosome study of 85 patients with myelodysplastic syndrome. 316 39

The efficacy of a methotrexate (MTX) block/thymidine release synchronization technique has been assessed in bone marrow cultures from patients with acute nonlymphocytic leukemia and myelodysplasia. In contrast to cultures of stimulated lymphocytes from normal individuals, no improvement in mitotic index (MI) or metaphase quality could be detected using this technique. Demonstration of an unchanged level of division in bone marrow cultures in the presence of MTX suggests that the technique is unsuitable for synchronization purposes in this tissue. The influence of preincubation prior to MTX exposure and duration of exposure to colcemid on MI and metaphase quality have also been examined.
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PMID:Methotrexate and bone marrow metaphases. 316 45

The clinical, hematologic, and phenotypic features of 28 patients with acute leukemia with megakaryocytic involvement (AMKL) were analyzed. The prevalence of this type of leukemia in the entire series was 11.6%, with a higher incidence among patients with acute transformation of a previous myeloproliferative disorder (MPD) (24%) than among the transformed myelodysplastic syndrome (13%) patients. The incidence in the "de novo" ANLL was 8% and 16% among secondary leukemias. The presence of bone marrow fibrosis together with low WBC and normal or increased platelet counts despite a severe anemia are the most relevant features in these patients who otherwise displayed an apparently poor prognosis. Megakaryoblasts were morphologically recognized more frequently in the acute transformations of MPD than in de novo ANLL. Only two cases were considered pure AMKL, and in the remaining 26 patients, megakaryoblasts coexisted with other granulomonocytic and/or erythroid populations. Antiglycoprotein IIIa (anti-GPIIIa) (C17) and anti-GPIIb/IIIa (CDw41-, J15-) antibodies are probably the best markers for AMKL, although the monoclonal antibody against GPIX (FMC25) was also positive in a majority of cases but in a lower percentage of cells. On the other hand, megakaryoblasts were generally negative for granulocytic or monocytic markers (CD13, CD14, CD15); the expression of HLA-DR antigens in these cells was variable. Our present results indicate that megakaryoblastic involvement is more common than previously recognized. This is true not only in acute transformed leukemias but also in de novo ANLL. Although the diagnosis of these cases should be based on megakaryocytic markers, it is often possible to suspect a diagnosis according to certain clinical and hematologic features.
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PMID:Leukemias with megakaryoblastic involvement: clinical, hematologic, and immunologic characteristics. 316 92

Seventeen patients with therapy-related myelodysplastic syndrome (t-MDS) or therapy-related acute nonlymphocytic leukemia (t-ANLL) were treated with single-agent high-dose cytarabine (HDAC; 1 to 3 g/m2 every 12 hours for 12 doses). The initial neoplasm was still present in eight patients when t-MDS/t-ANLL developed. Fifteen of the 16 patients with chromosomal abnormalities in bone marrow cells had loss or rearrangement of chromosomes 5 and/or 7. One patient had a t(15;17), and one had inadequate material for cytogenetic analysis. Twelve patients had normal metaphase cells (3% to 71%). Indications for HDAC therapy were progressive pancytopenia in 13 patients or rising blast count in four. Five patients died of marrow hypoplasia following therapy. Four others had refractory t-ANLL and died within the subsequent 5 months. Only one of ten patients with a poor performance status (PS greater than or equal to 2 using the ECOG scale) achieved a complete remission, but all seven patients with a good performance status (PS less than or equal to 1) had a complete remission. Hematologic remissions were achieved in 8 patients (47%) after one (6 patients) or two (2 patients) induction courses and were confirmed by recovery of a 100% normal marrow karyotype in six of the seven patients who were retested. Patients in remission received one to four consolidation courses with HDAC alternating with cytarabine/doxorubicin, but seven relapsed within 8 months (median remission duration, 5 months). In every case, the original chromosomal abnormality reappeared at relapse. HDAC has a high response rate for good-performance patients with t-MDS/t-ANLL, but complete remissions are short even when confirmed cytogenetically and consolidated intensively.
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PMID:Short remission durations in therapy-related leukemia despite cytogenetic complete responses to high-dose cytarabine. 316 10

A case of acute nonlymphocytic leukemia with a new translocation, t(2;7)(p13;q36), as the sole karyotypic abnormality is reported. The patient's leukemia evolved from a cytogenetically normal myelodysplastic syndrome of 4 years' duration. Following treatment the patient entered complete remission with loss of the cytogenetically abnormal clone. Subsequent bone marrow analyses showed recurrence of the myelodysplastic syndrome with a normal karyotype. Although both chromosomes 2 and 7 are known to be involved in nonrandom karyotypic changes in human cancer and leukemia, t(2;7)(p13;q36) has not been reported previously.
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PMID:Translocation (2;7)(p13;q36) in a case of acute nonlymphocytic leukemia evolving from a myelodysplastic syndrome. 318 21

Four cases with trisomy 11 as the sole chromosomal anomaly are reported, three with de novo acute nonlymphocytic leukemia (ANLL) and one with a myelodysplastic syndrome (MDS) after treatment for multiple myeloma. In reviewing the literature, we found 19 additional cases with trisomy 11 as the sole cytogenetic defect. All patients except one were reported to have ANLL or MDS. Thus, it seems that trisomy 11 is another rare but nonrandom chromosomal anomaly in ANLL and MDS. So far, no apparently characteristic clinical or cytologic signs have been found in these cases.
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PMID:Is trisomy 11 another nonrandom chromosomal anomaly in acute nonlymphocytic leukemia and myelodysplastic syndromes? 318 22

Twenty-nine adult patients with primary myelodysplastic syndromes (MDS) and an excess of marrow blasts were treated by aggressive chemotherapy while still in MDS phase (20 cases) or after progression to ANLL (9 cases). Median age was 47.5 (range 18-68). Twenty-eight patients received a combination of Rubidazone and Ara C and 1 received High dose Ara C. Fourteen patients (48%) achieved complete remission (CR), 5 (17%) were treatment failures (F) and 10 (35%) died during therapy induced aplasia (DA). Median disease free survival was 8.5 months. Median survival of the whole population was 6 months from the onset of treatment, and 17 months in patients achieving CR. These results were significantly less favorable than those obtained at our institution in de novo ANLL with the same chemotherapy regimens. No statistically significant prognostic factors of treatment outcome emerged but patients with normal cytogenetic findings seemed to have both a higher CR rate and longer remissions than patients with abnormal karyotypes. Patients under 50 did not have higher CR rates than older patients, although they had longer remissions (with 3 out of 6 CRs exceeding 2 years). Finally, treatment outcome and survival were identical in patients treated in the MDS phase and in those treated after progression to ANLL. Combination chemotherapy is a highly toxic approach in MDS and essentially seems to benefit younger patients with a normal karyotype, in whom some long remissions can be obtained.
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PMID:Aggressive chemotherapy in adult primary myelodysplastic syndromes. A report on 29 cases. 319 80

Nine cases of overt acute nonlymphocytic leukemia and four cases of preleukemia or a myelodysplastic syndrome, all related to intensive treatment with alkylating agents, were studied cytogenetically and investigated using a rapid and sensitive dot blot screening procedure for point mutations in the Ha-ras, Ki-ras, and N-ras protooncogenes within codons 12, 13, and 61. The technique involves a selective amplification of genomic DNA sequences containing the codon sequence of interest, in combination with oligonucleotide hybridization. Examining fractionated mononuclear cells from bone marrow or peripheral blood, an N-ras mutation at position 13 was observed in one patient with overt leukemia, resulting in a base change from GGT to TGT thus converting glycine to cysteine. The other cases exhibited no ras gene mutations. It is surprising that c-ras mutations are only occasionally observed in overt acute nonlymphocytic leukemia related to treatment with alkylating agents, as such abnormalities have often been observed in acute nonlymphocytic leukemia de novo, and as many alkylating agents are known to produce DNA adducts leading to point mutations and substitution of single amino acids. The fact that deletions of varying parts of the long arms of chromosomes 5 and 7 are observed in most cases of therapy-related acute nonlymphocytic leukemia and preleukemia, as confirmed by our own series of 71 patients, suggests that loss of heterozygosity for specific alleles on the two chromosomes, rather than activation of a protooncogene, could be an important step in leukemogenesis.
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PMID:Point mutation of the ras protooncogenes and chromosome aberrations in acute nonlymphocytic leukemia and preleukemia related to therapy with alkylating agents. 328 Jan 21

The use of chemical agents that induce differentiation of malignant cells to normal cells has held great promise as an adjunct to standard chemotherapy. In vitro data has shown that 13-cis-retinoic acid can differentiate certain leukemia cell lines (e.g., HL-60) into stable granulocyte cells. In this study, oral 13-cis-retinoic acid was administered to four patients with the myelodysplastic syndrome (MDS) and to four patients with acute nonlymphocytic leukemia (ANLL). None of the MDS patients showed an hematologic response to the drug, while three of four ANLL patients responded with normalized peripheral blood counts. The side effects of the drug at 80-120 mg/d (dry skin, cheilitis, epistaxis) were self limiting.
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PMID:Use of differentiation-inducing agents in the myelodysplastic syndrome and acute non-lymphocytic leukemia. 329 38

The arrangement of the immunoglobulin and T-cell receptor genes has been analysed in 72 cases of primary myelodysplastic syndrome and 17 cases of acute nonlymphocytic leukemia. DNA was extracted from bone marrow aspirates, digested with at least two restriction enzymes, and hybridised with probes for the joining region of the immunoglobulin heavy chain gene, the constant region of the T-cell receptor beta chain gene, and the joining region of the T-cell receptor gamma chain gene. All cases showed germline arrangements of the immunoglobulin and the T cell receptor genes. Thus, true interlineage infidelity, myeloid to lymphoid, is a rare occurrence in myelodysplasia and in myeloid leukemias.
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PMID:Absence of immunoglobulin and T-cell receptor gene rearrangements in myelodysplastic syndromes and acute nonlymphocytic leukemias. 329 39


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