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)

We determined the expression levels of the mdr1 and mdr3 multidrug-resistance genes (also known as PGY1 and PGY3, respectively) in peripheral blood cells from 69 adult patients with acute and chronic leukemias, using an RNase protection assay. Expression of mdr1 was found in samples from patients with acute nonlymphocytic leukemia (13 of 17), chronic myelocytic leukemia (CML, chronic phase, 10 of 10; blast crisis, three of four), acute lymphocytic leukemia (ALL, eight of 11), B-cell chronic lymphocytic leukemia (B-CLL, 17 of 17), hairy cell leukemia (HCL, one of two), and T-cell prolymphocytic leukemia (one of one), but not in B-cell prolymphocytic leukemia (B-PLL, 0 of seven). Expression of mdr3 was only detected in samples from B-cell lymphocytic leukemias: CML, lymphoid blast crisis (one of one), B-cell ALL (two of two), B-CLL (17 of 17), B-PLL (seven of seven), and HCL (two of two). In vitro drug uptake studies by on-line flow cytometry showed that in leukemia cells expressing either mdr1 or mdr3, the steady-state accumulation of daunorubicin could be significantly increased by addition of cyclosporine and, to a lesser extent, by verapamil. Because cyclosporine and verapamil are known as inhibitors of the mdr1-encoded P-glycoprotein drug-efflux pump, and because the mdr1 and mdr3 genes are highly homologous, our data suggest that the mdr3 gene encodes a functional drug pump in B-cell lymphocytic leukemias. The results of this study may have implications for clinical therapy for acute or chronic leukemias expressing the mdr1 or mdr3 gene, in particular, treatment with combinations of cytotoxic drugs plus agents that reverse multidrug resistance. Since mdr1 and mdr3 are frequently expressed in untreated as well as treated leukemia, such combination therapy should be considered for untreated patients as well as treated patients.
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PMID:Expression of mdr1 and mdr3 multidrug-resistance genes in human acute and chronic leukemias and association with stimulation of drug accumulation by cyclosporine. 197 61

Usefulness of DNA analysis in diagnosis of hematopoietic malignancy was discussed. Examination on the presence of rearrangement in immunoglobulin (Ig) and T cell receptor (TCR) was the first DNA analysis used for clinical diagnosis of lymphoid malignancy to determine the cell-lineage and clonality of proliferating lymphoid cells. One point mutation in ras oncogene has also been used to detect residual leukemic cells as well as diagnosis of the early relapse of leukemia, although not all leukemic cells have this mutation. Presence of BCR-abl fused gene is a genetic marker for Ph1 chromosome. Analysis of BCR-abl gene has made it possible to diagnose the Ph1 ALL and masked Ph1 CML. Development of PCR technique markedly increased the possibility for the use of DNA analysis in clinical medicine. In addition to Ph1 chromosome, various chromosomal abnormalities resulted in a reciprocal translocation between Ig or TCR gene and other genes in various lymphoid malignancies, such as Burkitt lymphoma and follicular lymphoma. These translocations can be analyzed by Southern hybridization and used for clinical diagnosis.
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PMID:[DNA diagnosis of human cancers: lymphoid malignancies and leukemia]. 198

We describe the properties of three monoclonal antibodies (McAbs) (21H73, 37G7 and 49C12) against K562 cell surface antigens correlated with differentiation induced by 12-O-tetradecanoyl phorbol-13-acetate (TPA). Each of the McAbs immunoprecipitated K562 cell surface antigen with molecular weight (MW) of approximately 51 kD, 82 kD or 92 kD, respectively. The antigens detected by McAbs 21H73 and 37G7 were not immunoprecipitated from K562 cells differentiated into monocyte-macrophages by TPA (K562-TPA). On the other hand, 49C12 immunoprecipitated an antigen with MW of 92 kD from K562-TPA cells, but not from undifferentiated K562 cells. To examine the distribution of these antigens among human haematopoietic stem cells, bone marrow cells were separated by the panning method using these McAbs and subjected to colony-forming assays. The McAb 21H73 reacted with CFU-mix and BFU-E but with neither CFU-E nor CFU-GM. CFU-mix and BFU-E were enriched approximately 6.2-14.7-fold and 2-fold by the panning procedure using 21H73, respectively. On the other hand, 37G7 reacted only with BFU-E, and 49C12 reacted with CFU-GM but not with any other haematopoietic progenitor cells. We also examined the reactivity of these McAbs with leukaemia cells freshly isolated from 26 patients. The antigen defined by 21H73 was not expressed on any leukaemia cells from patients except for cells from an acute lymphocytic leukaemia (ALL, L3) and a CML in blastic crisis. The McAb 37G7 reacted with several types of leukaemia cells. The antigen defined by 49C12 was expressed on almost all leukaemia cells isolated from patients. These results suggest that 21H73 allows purification and enrichment of normal haematopoietic pluripotent stem cells from both normal and leukaemia patients' bone marrow specimens, especially following the step to remove leukaemia cells and haematopoietic progenitor cells other than CFU-mix by using 37G7 and/or 49C12.
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PMID:Monoclonal antibodies raised against K562 cells reacted with human haematopoietic pluripotent stem cells. 203 Jun

The Ph chromosome was the first specific karyotype abnormality associated with a particular neoplastic disease in humans. For many years it was suspected that chromosome abnormalities might cause cancer by alteration of specific genes or their expression. Significant recent developments in our understanding of the molecular consequences of the Ph translocation strengthen that assumption. The Ph translocation generates a hybrid gene consisting of 5' regulatory, promotor, and exon sequences of the bcr gene on chromosome 22 fused to 3' exons and polyadenylation/termination sequences of the ABL proto-oncogene from chromosome 9. It is well established that fusion of bcr and abl genes plays a crucial role in the pathogenesis of CML and ALL. Molecular methods can therefore be used as diagnostic tools to detect the Ph chromosome. Presently, the model of oncogenesis provided by our knowledge of how the abl proto-oncogene becomes activated as a result of the Ph translocation is one of the clearest models of oncogene activation. Despite the progress made, many areas remain to be explored. One important question is, how the hybrid protein is involved in leukemia. Research aimed at investigating the normal function of abl and bcr may be important in efforts to understand their abnormal functioning in leukemia and to increase our understanding of the disease.
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PMID:Molecular insights into the Philadelphia translocation. 205 Jun

N-ras oncogenes activated by point mutation have been frequently detected in various types of human leukemias. Analysis of a large number of leukemias revealed that activated N-ras oncogenes were observed preferentially in AML, AMoL, T-ALL and Null-ALL but rarely in CML and B-cell leukemia. These results suggest that N-ras oncogene plays an important role in human leukemogenesis. Activated N-ras oncogenes were also detected in myelodysplastic syndrome (MDS) that is considered to be a preleukemic disease. MDS patients bearing an activated N-ras oncogene frequently showed leukemic progression of the disease, suggesting that an activated N-ras oncogene can be a critical factor for prognosis of MDS patients. Thus, detection of an activated N-ras oncogene is useful for diagnosis, prognostic evaluation and therapeutic decision. Recently, we demonstrated that detection of the minimal residual disease by analysis of N-ras oncogene can lead to improvement of the remission rate in leukemias. Moreover, we made it possible to screen N-ras oncogene by a sensitive non-radioactive method. Our research procedure seems to be a good model for clinical application of the molecular biological technique.
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PMID:[Activation of ras oncogene in myelodysplastic syndrome and acute myelogenous leukemia]. 205 67

A total of 293 cases of various types of leukaemia admitted in Central Hospital (Riyadh) were studied from January 1981 to December 1988. The incidence of leukaemia was worked out to be 0.13% of the total hospital population during this period. Acute non-lymphocytic leukaemia (ANLL) or acute myeloid leukaemia (AML) group was the most frequent (37.54%), followed by acute lymphocytic leukaemia (24.23%) followed by chronic myeloid leukaemia [corrected] (19.11%), chronic lymphocytic leukaemia (CLL) group (18.77%) and lymphosarcoma cell leukaemia (LSCL) (0.35%). Acute leukaemias were further classified into subtypes on the basis of FAB (French-American-British) classification. In ANLL or AML group, the pattern was M2 greater than M4 greater than M3 greater than M6 greater than M1 greater than M5. In ALL group, the pattern was L2 greater than L1 greater than L3. Among FAB subtypes of acute leukaemias, the pattern was L2 greater than M2 greater than M4 greater than M3 greater than M6 greater than M1 and L1 greater than L3 greater than M5. The age range of these patients was 5 years to 80 years; only 9 cases were less than 11 years of age. In childhood and young adults, acute leukaemias (ALL and AML) were the commonest types (particularly ALL was common in childhood), whereas CML was common in adults and CLL in old age. Males dominated the females in all the types of leukaemia (male to female ratio was 2.4:1). Out of 293 leukaemia cases, 149 (51.0%) were Saudi Arabs, the rest were expatriates. AML was found to be the most common type in central, western and southern Saudi Arabia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Leukaemia cases in Central Hospital, Riyadh (Saudi Arabia) 205 74

The CML-specific Philadelphia (Ph1) chromosome is relatively common cytogenetic abnormality of ALL, which has been shown 20% of adult ALL and 5% of child ALL. We analysed here the 12 patients of Ph1-positive ALL, aged 35 to 69-years old, who were experienced in our hospital for latest eight years. In comparison with Ph1-negative ALL, these 12 patients were elder and showed high peripheral and bone marrow leukemic cell counts. Of these, seven patients had 100% Ph1 abnormality in the bone marrow and another five patients showed mosaic marrow patterns of Ph1 and normal chromosomes. Remissioned eight cases had no more Ph1 abnormalities in their bone marrows. Our Ph1-positive ALL revealed B-cell lineage leukemia, since their surface phenotype were Ia+ and CD10+ and they have rearranged immunoglobulin JH genes. Four out of these nine patients had such gene rearrangement in the 5.8kb bcr (major BCR: M-BCR) as CML's patient had. Eight out of twelve Ph1-positive ALL patients (66.7%) achieved complete remission, but the prognosis was so bad since they had shorter remission duration (median 6.7 mos) and survival months (median 11.9 mos) than those of Ph1-negatives.
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PMID:[Philadelphia chromosome-positive adult acute lymphocytic leukemia]. 206 78

Chronic myeloid leukaemia (CML) is an excellent model for the study of molecular rearrangements caused by a cytogenetic anomaly associated with a disease. The formation of a Philadelphia chromosome by translocation between chromosomes 9 and 22 provokes the breaking and migration of a cellular oncogen (ABL), located in the 9q34 region, towards chromosome 22 and the 22q11 region where the PHL gene is situated. This gene is broken in the bcr area the rearrangements of which are specific to CML. The ABL and PHL genes fragments fuse together, creating a new hybrid gene which is transcribed into an 8.5 kilobase messenger RNA specific to CML. This RNA is translated into a 210 kilodalton protein whose abnormally high tyrosine kinase activity seems to contribute to the development of the disease. Genetic engineering techniques improve our understanding of CML molecular mechanisms and can be very useful to clinicians as they permit the diagnosis of CML in some cases devoid of chromosomal markers, and the detection of a possible relapse in marrow-grafted patients with a much greater sensitivity (one in 100,000 cells) than that of cytogenetics.
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PMID:[Chronic myeloid leukemia: from cytogenetics to molecular biology]. 209 36

From a bank of 50,000 HLA typed French bone marrow donors, 125 transplants have been performed since 1986, with HLA AB and DR--identical MLC--negative donors. The median age was 25 years and the diagnosis was CGL in 59 cases, ALL in 22 cases, AML in 17 cases, SAA in 7 cases, inborn errors in 7 cases and others in 13 cases. Most of the patients received a standard conditioning regimen according to their diagnosis. The prophylaxis of GVHD was methotrexate and cyclosporine A in 77 cases; in addition to this combination 44 patients received an anti-IL2 receptor monoclonal antibody from day +1 to day +28. There was no difference between the two groups as regards the incidence and severity of GVH or survival. The actuarial survival was 36% with a median follow up of 300 days. Unlike matched sibling grafts, the usual prognostic factors such as stage of disease or age were not found to significantly modify the incidence of GVHD, which was 75%. The results of matched unrelated donor transplants are reasonably good, but must be improved by a better selection of donors and better prevention of GVHD.
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PMID:Matched unrelated bone marrow transplants. Results from the French group (GEGMO). 209 99

Until recently, T cells were believed not to be involved in chronic myeloid leukemia. We describe an example of CML in T lymphoblastic crisis with massive generalized lymphadenopathy in which the blasts were CD2(+), CD5(+), and CD7(+), variably CD1(+) and CD3(+), and both responded to and could be induced to produce the T cell growth factor, interleukin-2. Additionally, the blasts were shown to contain the CML-related tyrosine kinase P210bcr-abl rather than the smaller kinase associated with Ph1(+) ALL. Finally, the participation of the T lymphoid lineage in the CML clone was proven by the presence of the same BCR rearrangement in blasts as in granulocytes, suggesting the existence of a bone marrow progenitor common to the T cell and myeloid lineages.
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PMID:Chronic myeloid leukemia arising in a progenitor common to T cells and myeloid cells. 216 6


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