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 April 1982 and July 1990, 101 patients underwent allogeneic or syngeneic bone marrow transplantation at the Mayo Clinic. This patient population consisted of 30 with acute nonlymphocytic leukemia, 25 with acute lymphoblastic leukemia, 29 with chronic granulocytic leukemia, and 17 with other diseases (aplastic anemia in 7, myelodysplastic syndrome in 5, and lymphoma in 5). The results achieved in our patients who underwent transplantation in first complete remission of both acute nonlymphocytic leukemia and acute lymphoblastic leukemia compare favorably with previously reported results. Only 1 of 15 patients (7%) with acute nonlymphocytic leukemia and 2 of 8 patients (25%) with acute lymphoblastic leukemia who underwent transplantation in first complete remission had a relapse. Thus, we recommend early bone marrow transplantation during initial complete remission for patients with either of these disorders who have adverse prognostic factors. In contrast, of 12 patients with either acute nonlymphocytic leukemia or acute lymphoblastic leukemia who underwent transplantation during relapse, 11 died within 6 months. Therefore, such patients should be offered new experimental treatments. Our patients with chronic granulocytic leukemia fared better when they underwent transplantation early during the course of their disease rather than during the accelerated or blast phase. Prospective studies are needed to determine the best approach in these patients.
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PMID:Mayo Clinic experience with allogeneic and syngeneic bone marrow transplantation, 1982 through 1990. 154 82

The karyotypes of 98 patients between the ages of 8 and 81 years with acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), myelodysplastic syndromes (MDS), and chronic myeloid leukemia (CML) are presented. Although the well-described cytogenetic abnormalities associated with particular FAB subtypes in the West were observed, certain important local differences were noted. In ALL, hyperdiploidy was rarely observed, whereas the Philadelphia chromosome was observed in 50% of abnormal karyotypes. In AML, the t(8;21) was infrequently observed in M2 case, whereas trisomy 4 and 6, rarely reported elsewhere, formed 12% of the abnormal cases. In MDS, the incidence of -5/5q- and/or -7/7q- was 83% of cases with aberrant cytogenetic findings. Neither i(17q) nor an extra Ph was seen in 26 cases of CML including 9 cases of accelerated phase/blast crisis. In addition, previously unreported cytogenetic abnormalities occurring as single cases are presented. These findings are discussed in the context of geographical heterogeneity of chromosomal abnormalities in leukemia and emphasize the importance of continued epidemiologic studies of cytogenetics in hematologic malignancies.
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PMID:Cytogenetic analysis of hematologic malignancies in Hong Kong. A study of 98 cases. 139 2

The expression of interleukin-2 receptors (IL-2R) was examined in 328 adult patients with non-T-cell (non-T) acute leukaemia and blast crisis of chronic myelocytic leukaemia (CML.BC) using two monoclonal antibodies, anti-Tac for IL-2R alpha chain (IL-2R alpha) and Mik beta 1 for IL-2R beta chain (IL-2R beta). Leukaemic cells in the following cases were positive for anti-Tac; 28/192 of acute myelocytic leukaemia (AML), 24/44 CML-BC, 4/28 CD19(+)CD10(-) acute lymphoblastic leukaemia (ALL), and 20/64 common ALL (c-ALL). IL-2R beta was not detected on leukaemic cells of any case examined. Eleven of IL-2R alpha(+) AML were derived from myelodysplastic syndrome. None of the IL-2R alpha positive leukaemic cells responded to exogenous recombinant human IL-2 (rhIL-2) in culture. In addition, IL-2R alpha expression on non-T leukaemic cells was closely correlated with coexpressing different lineage markers and the presence of the Philadelphia abnormality. Marked increase of serum soluble IL-2R alpha was demonstrated in the IL-2R alpha(+) patients examined. Clinically, the IL-2R alpha(+) patients showed significantly lower response to chemotherapy and poorer prognosis than IL-2R alpha(-) patients. Our results clearly indicate the diagnostic importance of IL-2R alpha expression in non-T acute leukaemia with a close relation to the particular cellular characteristics and the prognosis.
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PMID:Diagnostic and clinical importance of interleukin-2 receptor alpha chain expression on non-T-cell acute leukaemia cells. 158 Dec 11

Defects of 3q in bands q21 and q26 have been reported in more than 70 cases of acute nonlymphocytic leukemia (ANLL), myelodysplastic syndrome (MDS), and myeloproliferative disorder (MPD) in blast crisis. In this paper three additional patients are described: patient 1 with refractory anemia with excess of blasts in transformation (RAEB-T) and inv(3)(q21q26), patient 2 with RAEB-T and t(3;3)(q21;q26), and patient 3 with myelofibrosis with myeloid metaplasia (MMM) in blast crisis and inv(3)(q21q26). In addition to 3q rearrangements, monosomy 7 and del(7)(q22q36) were observed in patients 1 and 2, respectively. In the three patients, the most characteristic clinical features were elevated platelet counts, marked hyperplasia with dysplasia of the megakaryocytes, and poor prognosis. Although disturbance of thrombopoiesis was not systematically observed in all patients with t(3;3)(q21;q26), inv(3)(q21q26), and ins or dup(3)(q21----q26), study of the 77 cases reported and of the three cases presented here brings further evidence to the existence of a cytogenetic syndrome involving bands q21 and q26 simultaneously, which represents a subtype of ANLL, MDS, and MPD, characterized by normal or elevated platelet counts, hyperplasia with dysplasia of megakaryocytes, multilineage involvement, young median age of patients with MDS, preferential involvement of women in t(3;3), high incidence of chromosome 7 defects in MDS and ANLL, short duration of the MDS phase, no response to chemotherapy, short survival, and por prognosis.
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PMID:Three new cases of chromosome 3 rearrangement in bands q21 and q26 with abnormal thrombopoiesis bring further evidence to the existence of a 3q21q26 syndrome. 158 80

Two cases of unclassified chronic myeloproliferative disorders (UCMPD), diagnosed by hematological, cytogenetic and DNA analyses, are described. Case 1: a 63 year old female was admitted because of leukocytosis (96,800/microliters) and splenomegaly. Hematological examinations revealed an increase of the granulocytes in the peripheral blood and bone marrow. The neutrophil alkaline phosphatase (NAP) score was 121. The patient developed blast crisis after 12 months of the chronic phase. Case 2: a 48 year old male was presented with fever and leukocytosis (20,000/microliters). Hematological examinations revealed an increase of granulocytes in the peripheral blood and bone marrow. The NAP score was 33. Maturation-arrest in granulocytic series and morphological abnormalities of marrow cells were not observed in the two cases. Cytogenetic analysis of bone marrow cells disclosed 46, XX, i (17 q) in case 1 and 47, XY, +8 in case 2. Southern blot analysis using 3' bcr probe and TransProbe-1 showed no bcr rearrangement. These cases are thought to be valuable in order to clarify the relationship between UCMPD and CMPD such as Ph1 negative chronic myelocytic leukemia and myelodysplastic syndromes.
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PMID:[Two cases of unclassified chronic myeloproliferative disorders]. 160 19

Mutations of the p53 tumour suppressor gene have frequently been observed in several types of solid tumours and are believed to be implicated in the development of these tumours. To determine the relevance of p53 mutations in haematologic neoplasms, we performed polymerase chain reaction-single strand conformation polymorphism analysis on the p53 gene in 45 patients with various types of haematologic neoplasms. In exons 5-8 containing highly conserved regions, mobility shifts indicating sequence alterations were detected in four of the 45 patients, and subsequent sequencing was performed. A point mutation resulting in a novel stop codon was detected at codon 213 in one of 23 cases of chronic myelogenous leukaemia (one of five cases of blast crisis). Point mutations causing amino acid substitutions were detected in one of four cases of myelodysplastic syndrome at codon 195, one of three cases of adult T-cell leukaemia at codon 281, and one of eight cases of acute lymphoblastic leukaemia at codon 281, and these missense mutations were accompanied by loss of the wild type allele. Patients harbouring these nonsense and missense mutations were in advanced disease stages. These findings suggest that mutational inactivation of the p53 gene is infrequent but is involved in the tumorigenesis of several types of haematologic neoplasms at least in some cases.
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PMID:Mutations of the p53 tumour suppressor gene in haematologic neoplasms. 848 63

The retinoblastoma-susceptibility (Rb) gene is an antioncogene that is frequently altered in retinoblastomas, sarcomas, and some epithelial tumors. We examined the structure of the Rb gene by Southern blotting in 215 cases of leukemias and lymphomas of diverse phenotype and in 15 leukemic cell lines. In selected cases Rb protein expression was examined with specific monoclonal antibodies. Structural abnormalities of the Rb gene with absent protein expression were frequent in all types of human acute leukemia, but were particularly common (27% incidence) in M4 and M5 myeloid leukemia with monocytic differentiation and in Philadelphia chromosome (Ph1)-positive leukemia of lymphoid phenotype (11% to 29% incidence). Changes in Rb were observed early in the transition to acute leukemia in cases of myelodysplastic syndrome and in the accelerated phase of chronic myelocytic leukemia in transition to blast crisis. In one case, molecular changes in Rb could be correlated with leukemia remission and relapse. We conclude that the Rb antioncogene is commonly involved in the evolution of human acute leukemias, particularly in those of a monocytic phenotype and in lymphoid leukemia in which there is an antecedent alteration of the Ph1 chromosome.
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PMID:Abnormalities of the retinoblastoma gene in the pathogenesis of acute leukemia. 168 97

Background. Although colony-stimulating factors have been shown to accelerate recovery from severe neutropenia after intensive chemotherapy or bone marrow transplantation, their use in acute leukemia has been controversial because in vitro they stimulate leukemic colonies as well as normal granulocyte colonies. Methods. We conducted a prospective, randomized, controlled study to determine the safety and efficacy of recombinant human granulocyte colony-stimulating factor (CSF) after a standard course of intensive therapy in 108 patients with relapsed or refractory acute leukemia (67 with acute myelogenous leukemia, 30 with acute lymphocytic leukemia, 9 in blast crisis from chronic myelogenous leukemia, and 2 with acute leukemia arising from myelodysplastic syndromes). Treatment with granulocyte CSF (200 micrograms per square meter of body-surface area per day in a 30-minute infusion) was begun two days after the end of the chemotherapy and continued until the neutrophil count rose above 1500 per cubic millimeter. Results. Treatment with granulocyte CSF accelerated the recovery of neutrophils significantly (P less than 0.01), shortening it by about a week, but it had no effect on platelet recovery. Although the incidence of febrile episodes was almost the same, documented infections were significantly less frequent in the group treated with granulocyte CSF (P = 0.028). There was no evidence that granulocyte CSF accelerated the regrowth of leukemic cells. Fifty percent of 48 patients in the CSF group who could be evaluated and 36 percent of 50 controls had complete remission. The rate of relapse was almost the same in the two groups. Conclusions. It appears that recombinant human granulocyte CSF is safe in acute leukemia, accelerating neutrophil recovery and thereby reducing the incidence of documented infection without affecting the regrowth of leukemic cells. It should be used with caution, however, pending further confirmation of these early results.
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PMID:Effect of granulocyte colony-stimulating factor after intensive induction therapy in relapsed or refractory acute leukemia. 169 46

Relapse continues to be a problem after bone marrow transplantation (BMT) for hematologic malignancies, particularly in recipients of autologous or T-cell-depleted allogeneic grafts and in patients with advanced disease. Interferon (IFN) has shown antiproliferative activity in several malignant hematologic diseases and potentially may be of benefit when administered early after BMT when the number of residual cells is minimal. We tested in a phase I study the maximum tolerated daily dose of recombinant IFN alpha-2b in patients who had received a transplant for a disease at high risk for relapse (acute myeloid leukemia or non-Hodgkin's lymphoma beyond first remission, advanced myelodysplastic syndrome, acute lymphoblastic leukemia at any stage, chronic myeloid leukemia in accelerated or blast phase. Recombinant IFN alpha-2b was started at a dose of 0.5 x 10(6) IU/m2 and escalated by 0.5 x 10(6) IU/m2 in groups of three or four patients. The intention was to administer IFN as soon as stable engraftment after BMT was achieved (defined as an absolute neutrophil count of greater than 2.0 x 10(9)/L and platelet count greater than 100 x 10(9)/L for 5 consecutive days) and continued for 2 months. A total of 14 patients were enrolled after autologous (n = 3) or allogeneic (n = 11) BMT. Dose-limiting toxicity was myelosuppression. Significant (grade 2 to 4) neutropenia and thrombocytopenia led to discontinuation or dose reduction in five of eight patients receiving 1.5 x 10(6) or 2 x 10(6) IU/m2 IFN. Mild to moderate (grade 1 or 2) anorexia, weight loss, and fatigue occurred in the majority of patients independent of the IFN dose. De novo acute GVHD responsive to steroid treatment developed in 3 of 11 allograft recipients. Natural killer (NK) cell function was low before IFN treatment and was not improved with the cytokine. Conversely, interleukin-2-activated NK cells showed normal function even before starting IFN and no change was seen during IFN treatment. Clonogenic hematopoietic progenitor studies showed depression of all progenitor lines (colony-forming unit [CFU]-granulocyte, erythroid, monocyte, megakaryocyte, CFU granulocyte-macrophage, burst-forming unit-erythroid) by IFN at all dose levels except at 0.5 x 10(6) IU/m2. Considering this result and the incidence and severity of marrow depression seen at doses greater than 1.0 x 10(6) IU/m2, we would consider this the maximum dose safely tolerated if IFN alpha-2b is administered in this setting for a prolonged course on a daily basis.
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PMID:Treatment with recombinant interferon (alpha-2b) early after bone marrow transplantation in patients at high risk for relapse [corrected]. 174 91

Three patients, one with Philadelphia (Ph) chromosome positive chronic myelocytic leukemia (CML) and two with primary acquired myelodysplastic syndromes (MDS), have been identified to have a t(3;21)(q26;q22). In the patient with CML, the t(3;21) was detected only in the blast phase. The t(3;21) as the sole abnormality appeared at presentation of MDS [refractory anemia with excess blasts (RAEB)] in one patient and remained as such when progression to RAEB in transformation (RAEB-t) occurred. The other patient with MDS had the t(3;21), in addition to other changes, during the progression of the disease. Thus, t(3;21) may characterize myeloid crises of clonal hematopoietic stem cell disorders (HSCD) and indicates a poor prognosis. As a primary cytogenetic event it may be also involved in the genesis of myelodysplasia with subsequent leukemic transformation.
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PMID:Translocation (3;21) characterizes crises in myeloid stem cell disorders. 175 92


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