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)

Sixty patients with adult acute lymphocytic leukemia (ALL) and 40 patients with blastic crisis of chronic myeloid leukemia (CML . BC) were randomly allocated by envelope method to receive either vindesine (VDS; 2 mg/m2 i.v., twice or once weekly) or vincristine (VCR; 1.2 mg/m2 i.v., once weekly) in combination with prednisolone (Pred; 40 mg/m2 p.o., daily). Out of 100 patients entered, 53 patients with ALL and 34 patients with CML . BC were evaluable. Remissions for ALL were seen in 20 of 25 patients (80.0%; 12 CRs and 8 PRs) treated with VDS regimen, and in 17 of 28 patients (60.7%; 7 CRs and 10 PRs) treated with VCR regimen, respectively. For CML . BC, however, remission rates for VDS regimen (42.1%; 5 CRs and 3 PRs in 19 patients) and for VCR regimen (40.0%; 2 CRs and 4 PRs in 15 patients) were equivalent. Overall remission rates of VDS regimen for both diseases, twice weekly regimen (65.5%; 11 CRs and 8 PRs in 29 patients) and once weekly regimen (60.0%; 6 CRs and 3 PRs in 15 patients) were similar. Patients treated with either regimen experienced high incidence of neurotoxicity. Neurotoxic disturbance appeared severer in patients treated with VCR regimen. Incidence of leukopenia and alopecia was high in patients treated with VDS regimen. These data suggest that VDS in combination with Pred is comparable-rather superior-to VCR in combination with Pred for adult ALL and CML . BC. Less neurotoxic and sufficiently effective dosage of VDS is considered to be 2 mg/m2, once weekly.
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PMID:[A randomized controlled study on vindesine and vincristine in combination with prednisolone in the treatment of adult acute lymphocytic leukemia and blastic crisis of chronic myeloid leukemia]. 658 Aug 40

Between June 1991 and September 1992, 80 patients with adult acute lymphoblastic leukemia (ALL) (newly diagnosed, n = 68; relapsed or refractory ALL, n = 7; lymphoid blast transformation of Philadelphia chromosome-positive chronic myelogenous leukemia [LT-CML], n = 5) were managed with a combination regimen consisting of idarubicin 36, 20, or 10 mg/m2 plus vincristine, L-asparaginase, and prednisolone (IVAP-1, -2, -3). Three patients with LT-CML and four with relapsing ALL had a complete remission. In the group of newly diagnosed patients aged 15 to 60 years treated with IVAP-1, the complete remission rate was only 44% due to the high incidence of toxic deaths. In contrast, 39 of 44 cases who subsequently received IVAP-2 achieved a complete remission (89%, P = .001), as did 62% of elderly patients who received IVAP-3. Hematologic and nonhematologic toxicity was significantly reduced with IVAP-2 compared with IVAP-1. The use of recombinant human granulocyte colony-stimulating factor in 24 patients was not associated with a reduced duration of granulocytopenia less than 0.5 x 10(9)/L, although there was a lower incidence of documented infections in patients receiving granulocyte colony-stimulating factor than in controls. Post-remission intensification with idarubicin-based courses, high-dose therapy with autologous bone marrow stem cell rescue, and rotational weekly therapy was feasible and its toxicity was manageable. These preliminary findings indicate that IVAP-2 (idarubicin 20 mg/m2) is a highly effective and well-tolerated regimen for remission induction of adult ALL.
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PMID:Intensive therapy for adult acute lymphoblastic leukemia: preliminary results of the idarubicin/vincristine/L-asparaginase/prednisolone regimen. 750 63

A basic helix-loop-helix phosphoprotein gene, G0S8, was recently isolated by differential screening of cDNA from human blood mononuclear cells stimulated with a T cell mitogen and cycloheximide. In this study, G0S8 expression was examined in normal and malignant hematopoietic cells by Northern blot analysis and reverse transcription-polymerase chain reaction (RT-PCR). G0S8 expression was observed in most fresh samples of acute myelogenous leukemia (AML) (28/30) and most cases of adult acute lymphoblastic leukemia (ALL) (9/11) regardless of clinical classification. G0S8 mRNA was also detected in all cases tested of chronic myelogenous leukemia (CML) in blast crisis. However, G0S8 expression was not detected in CML patients in chronic phase, nor in normal bone marrow or other hematopoietic cells. G0S8 has been mapped using fluorescence in situ hybridization (FISH) to human chromosome 1q31, the same site reported for the B cell homolog BL34/1R20 and within a region implicated in the development of hematological malignancies. The consistent observation of G0S8 mRNA in patient samples of acute leukemia suggests that G0S8 expression may either play a role in leukemogenesis or represent a common consequence of dysregulated growth.
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PMID:Differential expression of a basic helix-loop-helix phosphoprotein gene, G0S8, in acute leukemia and localization to human chromosome 1q31. 764 15

The sensitivity and clinical utility of the polymerase chain reaction (PCR) assay for the detection of BCR-ABL gene rearrangement was compared to conventional cytogenetics for the Philadelphia chromosome (Ph1) in adult acute lymphoblastic leukemia (ALL) patients entered onto a single clinical trial. Ninety-three patients had evaluable PCR assays for both the p190bcr-abl and p210bcr-abl type of BCR-ABL gene rearrangements. Twenty-one of 93 patients (23%) were positive for the BCR-ABL rearrangement by the PCR assay. Fourteen of these patients had the p210brc-abl BCR-ABL rearrangement characteristically seen in CML patients, while seven had the p190bcr-abl rearrangement seen in ALL alone. Of 61 patients analyzed, both with conventional cytogenetics and PCR, eight (13%) were positive for the Ph1, while 14 (23%) were positive for the BCR-ABL rearrangement by the PCR assay. Discordance between the PCR assay and cytogenetics occurred in eight cases where the PCR assay was positive and the cytogenetics negative, and two cases where the PCR assay was negative and cytogenetics positive. PCR positivity did not correlate with treatment response, survival, or relapse-free survival, but there was a higher percentage of L2 FAB morphology in the PCR+ cases compared to the PCR-cases (67 vs. 28%, p = 0.003). In addition, the data suggested that patients with a p190bcr-abl rearrangement have a better response to induction therapy, but a worse relapse-free survival compared to patients with a p210bcr-abl breakpoint, but these differences were not statistically significant. These data suggest that PCR and conventional cytogenetics may provide complementary information, since there appear to be a subset of patients who are Ph1-negative yet BCR-ABL positive by PCR. Further studies will be required to determine the prognostic significance of the detailed information about BCR-ABL breakpoints that is available from the PCR assay.
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PMID:Detection of BCR-ABL fusion genes in adult acute lymphoblastic leukemia by the polymerase chain reaction. 793 64

We herein report a rare case of Ph chromosome-negative acute T-lymphoblastic leukemia (T-ALL) with a classical BCR rearrangement seen in chronic myelogenous leukemia (CML). There were no clinical or morphologic features to suggest a previous chronic phase of CML. The importance of a full analysis of the BCR gene in the case of adult acute lymphoblastic leukemia (ALL), especially in T-ALL, are discussed.
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PMID:De novo Ph-negative acute T-lymphoblastic leukemia with BCR gene rearrangement. 809 40

Philadelphia chromosome (Ph1) is detected in more than 95% of chronic myelogenous leukemia (CML) and approximately 20% of adult acute lymphocytic leukemia (ALL). In order to discriminate Ph1-positive ALL from Ph1-positive CML as a clinical entity, I studied on biological and genetic characteristics of Ph1-positive ALL cells. Two cases out of 11 Ph1-positive ALL showed hybrid leukemia phenotypes; in one hybrid case simultaneous proliferation of lymphoid and myeloid blast cells was observed and contained rearranged alleles of heavy chain genes, thus indicating that both blast cells might originate from a common precursor. Two Ph1-positive ALL cell lines (TOM-1 and ALL-MIK) were established from two patients and were investigated for their differentiation potential in vitro. Both cell lines showed the potency to differentiate into monocytic lineage cells, thus suggesting that these Ph1-positive ALL cells might reside at the stage of multipotent progenitor cell along hematopoietic cell differentiation. As to Ph1-chromosome, 4 out of 9 Ph1-positive ALL cases showed rearrangements within the classical sequence (M-bcr), similar to those in CML cases. Two out of 5 cases without rearrangement of M-bcr showed breakpoints in the first intron of the BCR gene. In the rest of 3 cases, BCR-ABL rearrangement was not detected by Southern analysis. However, a leukemic cell line established from one of these patients (TOM-1) were contained P190bcr-abl mRNA as analyzed through RT-PCR. Thus, breakpoints of the BCR gene in Ph1-positive ALL cases were heterogenous, in contrast to those of CML. Then, I investigated whether or not the activation of transforming genes other than BCR-ABL might be involved in pathogenesis of Ph1-positive ALL. Three out of 15 Ph1-negative ALL cases showed the mutations of RAS gene by the PCR. However, no activated oncogene was detected in Ph1-positive ALL cases by both DNA transfection assay and PCR.
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PMID:[The cellular and molecular-biological studies on Philadelphia chromosome-positive acute lymphocytic leukemia]. 831 33

We performed cytogenetic and molecular analysis of the BCR-ABL rearrangement by polymerase chain reaction (PCR) in 39 consecutive cases of adult acute lymphoblastic leukemia (ALL). Eleven patients had a Philadelphia (Ph) chromosome. Thirteen patients had a BCR-ABL rearrangement, involving minor breakpoint cluster region (m-bcr, situated in intron 1 of the BCR gene) in 11 cases, and major breakpoint cluster region (M-bcr, 'specific' of chronic myeloid leukemia) in the remaining two cases. All of the 12 BCR-ABL cases studied immunologically were of early B, CALLA-positive immunophenotype. The 13 BCR-ABL positive cases included the 11 Ph-positive cases, and two patients with normal karyotype at diagnosis. In the two Ph-negative BCR-positive cases, seven (patient 1) and 18 (patient 2) mitoses had been examined at diagnosis. In patient 1, Ph negativity at diagnosis could certainly be explained by the small number of mitoses analyzed, as a Ph chromosome was found at relapse. This was less probable in patient 2, who raised the issue of whether authentic Ph-negative BCR-ABL-positive ALL exists (as in the chronic myeloid leukemia model) or not. Whatever the explanation, our results suggest that molecular detection of BCR-ABL should be more widely used in B-lineage ALL.
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PMID:Philadelphia negative, BCR-ABL positive adult acute lymphoblastic leukemia (ALL) in 2 of 39 patients with combined cytogenetic and molecular analysis. 832 Oct 20

Estrogen appears to be a negative regulator of normal hematopoiesis. Chromosome 6q, which contains the estrogen receptor (ER) gene, is frequently altered in human hematopoietic neoplasms. The ER gene, which has growth and metastasis suppressor activity in many different cell types, is inactivated by promoter methylation in some ER-negative breast tumors and 100% of colorectal tumors. We now report that the promoter region of the ER gene is aberrantly methylated in 86% of human hematopoietic tumors, including 8 of 9 pediatric acute lymphocytic leukemia, 17 of 18 adult acute lymphocytic leukemia, 21 of 23 adult acute myelogenous leukemia, 3 of 6 chronic phase chronic myelogenous leukemia, 9 of 9 blast crisis chronic myelogenous leukemia and 5 of 8 lymphomas. This methylation event was also present in all nine leukemia cell lines examined, where it was associated with very low or absent ER expression. In addition, rat and mouse leukemia cell line also exhibited this change, indicating that ER CpG island methylation in leukemias is conserved among species. Our results suggest that ER CpG island methylation could be an important step in the genesis of human hematopoietic neoplasms and might be a useful molecular marker for monitoring the clinical status of these diseases.
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PMID:The estrogen receptor CpG island is methylated in most hematopoietic neoplasms. 864 Jul 88

Expression of the myeloperoxidase (MPO) gene at the mRNA level is a better lineage marker than enzymatic activity in early myeloid precursors and their leukemic counterparts. Its diagnostic use depends on the specificity of expression for myeloblasts and its absence in blasts of lymphoid lineage. The present study investigates MPO mRNA expression in adult acute lymphoblastic leukemia (ALL), using reverse transcription-polymerase chain reaction. Of a total of 13 cases, six were found to have blasts positive for MPO mRNA; in all of these cases, the blasts were cytochemically negative for MPO. This unexpected finding of MPO mRNA positivity in six of 13 cases was further investigated at the molecular level. Bcr gene rearrangement analysis was positive in all six cases for the bcr breakpoint diagnostic of chronic myelogenous leukemia (CML). Only three of these six cases were cytogenetically positive for a Philadelphia (Ph) chromosome. Based on molecular analysis, these cases are considered as CML presenting in blast crisis of lymphoid lineage, as opposed to de novo ALL. The remaining seven cases were Ph negative at the cytogenetic and molecular levels; the leukemic blasts were MPO mRNA negative, confirming the lack of MPO gene expression in de novo ALL.
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PMID:Myeloperoxidase mRNA analysis in acute lymphoblastic leukemia. 927 91

A number of fusion genes have been identified by study of acquired chromosomal translocations. Their detailed characterization has provided insights into mechanisms of leukaemogenesis and has enabled the development of molecular methods to assist in the diagnosis and monitoring of residual disease after treatment. The TEL-AML1 fusion gene is associated with a cryptic t(12:21)(p12:q22) translocation, and is the commonest known genetic abnormality in childhood B-cell precursor acute lymphoblastic leukaemia (ALL), occurring in about 25% of cases. We have used RT-PCR, followed by Southern blotting and direct sequencing, to establish the incidence of TEL-AML1 rearrangement in 131 adults with acute leukaemia (101 with ALL and 30 with chronic myeloid leukaemia in blastic crisis). Three patients were positive for TEL-AML1 transcripts. All three had common-ALL. All other patients were negative for TEL-AML1. We conclude that the TEL-AML1 fusion gene is found in adult ALL, though less commonly than in children.
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PMID:TEL-AML1 fusion in acute lymphoblastic leukaemia of adults. M.R.C. Adult Leukaemia Working Party. 898 44


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