Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

We report two patients with a myelodysplastic syndrome and the Philadelphia (Ph) chromosome. The first patient was a 73-year-old man who was diagnosed as having a chronic myelomonocytic leukemia in combination with features suggestive of a myeloproliferative syndrome. Chromosomal analysis showed a normal karyotype in the majority of cells, mixed with metaphases containing a standard Ph translocation, t(9;22)(q34;q11), as well as a translocation between chromosome 4 and 6: t(4;6)(p15;p12). Southern blot analysis showed breakpoint cluster region rearrangement as observed in classic chronic myeloid leukemia. The second patient was a 63-year-old man with a myelodysplastic syndrome, type refractory anemia. Cytogenetic study of bone marrow cells at the time of diagnosis revealed a normal karyotype: 46,XY. The initial myelodysplastic syndrome evolved to a myeloproliferative phase with progressive leukocytosis and thrombocytosis. During the terminal phase the Ph chromosome was discovered in 100% of the examined cells. We discuss the correlation between MDS and myeloproliferative diseases, the de novo acquisition of the Ph chromosome during the course of a myelodysplastic syndrome, and review the literature.
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PMID:Cytogenetic and molecular studies of the Philadelphia translocation in myelodysplastic syndromes. Report of two cases and review of the literature. 158 81

Translocation (6;9)(p23;q34) is a cytogenetic aberration that can be found in specific subtypes of both acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). This translocation is associated with an unfavourable prognosis. Recently, the genes involved in the t(6;9) were isolated and characterized. Breakpoints in both the dek gene on chromosome 6 and the can gene on chromosome 9 appear to occur in defined regions, which allows us to diagnose this type of leukemia at the molecular level. Moreover, because of the translocation a chimeric dek-can mRNA is formed which, as we show here, is an additional target for diagnosis via cDNA-preparation and the polymerase chain reaction (PCR). We studied 17 patients whose blood cells and/or bone marrow cells showed a t(6;9) with karyotypic analysis. Fourteen patients suffered from AML, one patient had a refractory anemia with excess of blasts in transformation (RAEBt), one patient had an acute myelofibrosis (AMF), and one patient a chronic myeloid leukemia (CML). In nine cases studies at the DNA and RNA levels were possible while in seven cases only the DNA could be analyzed. In one case only RNA was available. Conventional Southern blot analysis showed the presence of rearrangements of both the dek gene and the can gene. In both genes, breakpoints cluster in one intron in the patients investigated. The presence of a consistent chimeric dek-can product after cDNA preparation followed by the PCR was demonstrated. We conclude from our data that the t(6;9) is found in myeloproliferative disorders with typical clinical characteristics. This translocation results in highly consistent abnormalities at the molecular level.
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PMID:The translocation (6;9) (p23;q34) shows consistent rearrangement of two genes and defines a myeloproliferative disorder with specific clinical features. 158 43

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

For severe aplastic anemia and several malignant hemopathies allogeneic bone marrow transplantation is the only treatment with curative potential. This is the case for chronic myelogenous leukemia, the myelodysplastic syndromes and probably multiple myeloma and chronic lymphocytic leukemia. It seems also the best therapeutic option for young adults who suffer from acute leukemia and for whom an adequate family donor is available. We review here the main complications of the procedure. Their better knowledge and the way to prevent and to treat them has decreased the mortality and morbidity of this treatment which is mostly successful when applied on patients in the early phase of their disease. Recently, the availability of HLA typed registered volunteers has extended the applicability of allogeneic bone marrow transplantation for those patients who lack adequate familial donors.
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PMID:[Bone marrow allograft in adults hemopathies. The Team of the Sterile Unit]. 160 90

Diagnosing chronic myeloproliferative disorders (CMPD) can be difficult because of overlap and possible transitions between the different conditions and their similarity to reactive myeloproliferations. DNA analysis was applied to improve differentiation of CMPDs. All subtypes of CMPD analyzed, including chronic myeloid leukemia, agnogenic myeloid metaplasia, polycythemia vera, and essential thrombocythemia, had in common that granulocytes and bone marrow cells were clonal in origin, as shown by X chromosome-linked DNA polymorphism in conjunction with methylation patterns (n = 32). Reactive myeloproliferations, by contrast, showed polyclonal inactivation patterns. Clonality could not distinguish CMPD from cases of myelodysplastic syndrome because the latter (n = 7) also exhibited clonal hematopoiesis. Because of their clonal origin, peripheral granulocytes were used in all cases (n = 201) to detect bcr gene rearrangement. Despite possible morphologic overlap between different types of CMPD, bcr gene rearrangement was specific for chronic myeloid leukemia and could be applied to differentiate chronic myeloid leukemia from other CMPDs in cases of equivocal morphologic diagnosis. Chronic myeloproliferative disorders represent clonal hemopoietic diseases that probably have specific underlying genetic defects. Thus DNA analysis can aid substantially in the differential diagnosis of CMPD.
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PMID:DNA analysis to aid in the diagnosis of chronic myeloproliferative disorders. 161 25

Myelodysplastic syndrome (refractory anemia with excess of blasts; RAEB) with marked basophilia and eosinophilia is described. An 82-year-old male was admitted to our hospital because of severe normocytic normochromic anemia (Hb 5.6 g/dl). The white cell count was 9,200/microliters with marked basophilia (34.5%) and eosinophilia (19.5%). The bone marrow aspiration also revealed both basophilia and eosinophilia, with blast contents of 9%. Diagnosis of RAEB was established. Although the treatment with red cell transfusion and ubenimex (Bastatin) was started, anemia was not improved. A karyotype of the bone marrow cells from this patient showed 47, XY, +8, i (17q), which has been observed as additional chromosomal abnormalities in blastic crisis of chronic myelogenous leukemia. The diagnosis of CML was not compatible with this case, because Ph1 chromosome and bcr gene rearrangement were negative. It is concluded that eosinophilia and basophilia might be derived from clonal abnormalities associated with MDS.
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PMID:[Myelodysplastic syndrome associated with marked eosinophilia and basophilia]. 163 67

Mast cell growth factor (MGF), the ligand for the c-kit receptor, has been shown to be a hematopoietic growth factor that preferentially stimulates the proliferation of immature hematopoietic progenitor cells (HPC). We studied the effect of MGF on the in vitro growth of clonogenic leukemic precursor cells in the presence or absence of interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), and/or erythropoietin (EPO). Leukemic blood and bone marrow cells from patients with various types of acute myeloid leukemia (AML), chronic myeloid leukemia (CML) in chronic phase, as well as bone marrow samples from patients with myelodysplastic syndromes (MDS) were studied. MGF as a single factor did not induce significant colony formation by clonogenic leukemic precursor cells. In the presence of IL-3 and/or GM-CSF, MGF weakly stimulated the colony formation by clonogenic precursor cells from patients with AML. In contrast, in the presence of IL-3 and/or GM-CSF, MGF strongly induced both size and number of leukemic colonies from patients with CML in chronic phase. Furthermore, in the presence of EPO, MGF strongly stimulated erythroid colony formation by CML precursor cells. Cytogenetic analysis of the colonies showed that all metaphases after 1 week of culture were derived from the leukemic clone. In patients with MDS, MGF strongly stimulated myeloid colony formation in the presence of IL-3 and/or GM-CSF (up to fourfold), and erythroid colony formation in the presence of EPO (up to eightfold). Not only the number, but also the size of the colonies increased. In the presence of MGF, the percentage of normal metaphases increased in three patients tested after 1 week of culture compared with the initial suspension, suggesting that the normal HPC were preferentially stimulated compared with the preleukemic precursor cells. In the absence of exogenous EPO and in the presence of 10% human AB serum, MGF in the presence of IL-3 and/or GM-CSF induced erythroid colony formation from normal bone marrow and patients with MDS or CML, illustrating that MGF greatly diminished the EPO requirement for erythroid differentiation. These results indicate that MGF may be a candidate as a hematopoietic growth factor to stimulate normal hematopoiesis in patients with acute myeloid leukemia, or with myelodysplastic syndromes.
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PMID:Effect of mast cell growth factor (c-kit ligand) on clonogenic leukemic precursor cells. 163 26

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


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