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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 report a case of acute leukemia in which studies at presentation showed both myeloid and lymphoid cell surface markers. At relapse membrane markers studies were consistent with a leukemia of B-lymphoid lineage. However, immunoglobulin (Ig) and T cell receptor (TCR) beta chain genes were both found in a rearranged configuration. The majority of metaphases from the leukemic cells at presentation showed the Philadelphia chromosome, t(9;22)(q34;q11), whereas a minority were normal. At relapse both Ph-positive and -negative metaphases were still present in the bone marrow but some of the Ph-negative metaphases had acquired an additional chromosome #19 [47,XY, + 19]. Southern analysis of DNA from leukemic bone marrow cells at diagnosis showed no rearrangement of breakpoint cluster region (bcr). There was no bcr-abl chimeric mRNA typical of Ph-positive chronic myeloid leukemia (CML). However, the cells expressed an abl-related protein of Mr 190 kd with enhanced tyrosine kinase activity. Leukemic cell metaphases were studied by the technique of in situ hybridization with probes for C-lambda, sis, abl, and 5' bcr. The c-abl probe mapped to chromosome 22q11 in Ph-positive metaphases. The 5' bcr probe mapped to 9q+ in the Ph-positive metaphases and the C-lambda gene mapped to the Ph chromosome. Thus, the genomic breakpoint in this patient must lie upstream of the BCR defined by study of Ph-positive CML and downstream of the C-lambda gene locus. We speculate that the Ph-negative cells in this patient may represent a leukemic proliferation susceptible to acquisition of specific chromosomal changes.
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PMID:The genomic breakpoint in a patient with Philadelphia-positive acute leukemia is 5' of the breakpoint cluster region. 325 55

Nonrandom patterns of chromosome abnormality in tumors are providing clues to the location of oncogenes and their activation mechanisms. Studies of translocations in Burkitt's lymphoma cells have shown that the c-myc proto-oncogene is consistently juxtaposed with a rearranged and transcriptionally active immunoglobulin gene locus, with resultant myc gene deregulation. In other B cell tumors, translocations appear to bring previously unrecognized oncogenes (bcl-1, bcl-2) into similar association with the immunoglobulin heavy-chain locus. T cell receptor genes may also "activate" known and unknown oncogenes after chromosome translocation. In chronic myelogenous leukemia, the translocated c-abl oncogene forms a "hybrid" gene in its new location on the Philadelphia chromosome, with altered function. Gene amplification units, seen as cytogenetically homogeneous staining regions in chromosomes or as double-minute bodies in metaphases, can represent multiple copies of oncogenes and be important in late stages of tumor progression. Other significant alterations in gene dosage, recognized as gain or loss of all or part of a specific chromosome, also occur in human neoplasms, but their specific role in carcinogenesis is largely undefined.
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PMID:Chromosomal approaches to the molecular basis of neoplasia. 332 6

Six patients with Philadelphia-positive (Ph1+) acute nonlymphocytic leukemia (ANLL) were studied by morphological, immunological, cytogenetic, and molecular techniques. Seven Ph1+ acute lymphocytic leukemia (ALL) cases were also studied for comparison. Three of ANLL cases were classified in M1, M2, and M4 groups of the FAB nomenclature, while the three other cases do not fit with any FAB subgroup and are described as M0. Immunophenotypical marker studies, double immunolabeling, and combined immunological and cytogenetic studies of metaphases showed that these ANLL expressed several lineage differentiation antigens. Rearrangements of immunoglobulin heavy chain gene (C mu) were detected in the six ANLL cases and in the seven ALL cases studied, as well as, in most cases, rearrangement of T cell receptor beta chain genes and/or T cell rearranging gamma genes. The results favored the assumption that the Ph1 translocation originated from a multipotent stem cell in Ph1+ ANLL. A common t(9;22) translocation was found in all cases, and additional chromosomal abnormalities were present in the six ANLL cases and in five of the seven ALL cases. Molecular studies of bcr gene configuration and c-abl transcription allowed two groups of Ph1+ ANLL to be distinguished. Three cases had bcr rearrangement and c-abl mRNA expression comparable to those reported in Ph1+ chronic myeloid leukemia, while three others had not detectable bcr rearrangement and a 7.2-7.5 kb c-abl mRNA. The existence of Ph1+ ALL with and without classical bcr rearrangement was confirmed.
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PMID:Philadelphia-positive acute leukemia: lineage promiscuity and inconsistently rearranged breakpoint cluster region. 337 67

We have examined the immunophenotype and genotype of leukemic cells from 20 patients with the blastic phase of chronic myelogenous leukemia (CML), which is known to arise from a pluripotential hematopoietic stem cell. The phenotypic analysis of surface antigens with a panel of lineage-specific monoclonal antibodies revealed that six of 20 cases expressed phenotypes of lymphoid blastic transformation with pre-B cell markers. One of these cases was shown to coexpress cluster designation 2 of T cell marker on the same cells by two-color immunofluorescence analysis. Eight cases, including two cases that also had a megakaryocytic component, showed phenotypes expressing differentiation antigens of myeloid series. Three expressed a phenotype of megakaryoblastic transformation. The remaining three cases had no surface marker characteristic of any cellular lineage. The genotypic analysis by Southern blot hybridization showed that immunoglobulin heavy chain genes were rearranged in all of six lymphoid blastic transformations and that rearrangement of a T cell receptor beta chain gene was present in only one lymphoid blastic transformation that had no T cell surface marker. DNA samples in all cases of nonlymphoid blastic transformation were retained in the germ line configuration for both immunoglobulin and T cell receptor genes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Analysis of immunophenotype, genotype, and lineage fidelity in blastic transformation of chronic myelogenous leukemia: a study of 20 cases. 342 82

Immunoglobulin and T cell receptor gene mapping were undertaken in 10 patients during both chronic and blastic phases of chronic granulocytic leukemia. Twenty percent were shown to undergo lymphoblastic transformation. DNA changes did not predict blastic transformation or those who would respond favourably to treatment with vincristine and prednisone.
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PMID:DNA changes during blastic transformation in chronic granulocytic leukemia. 348 Oct 64

To study the possible involvement of T lymphocytes in Philadelphia chromosome (Ph)-positive chronic myelocytic leukemia (CML) we analyzed the arrangement of the bcr gene in T cell and non-T cell samples of 12 CML patients. Although all the patients showed bcr rearrangements in non-T cell fractions, T cell populations lacked respective gene recombinations. Moreover, by Southern blot analyses using T cell receptor beta chain sequences our data indicate polyclonality of T cell samples from 11 of 12 cases; in one patient a clonal T cell population could be identified. These results suggest that T lineages of most Ph-positive CML patients are not derived from pluripotent stem cells involved in leukemogenesis and thus confirm previous investigations based on cytogenetic or glucose-6-phosphate dehydrogenase analyses. The demonstration of polyclonal T cell populations may reflect persistence of stem cells committed to differentiate only into T cells.
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PMID:T lymphocytes lack rearrangement of the bcr gene in Philadelphia chromosome-positive chronic myelocytic leukemia. 349 3

We established a novel T cell line, designated TK-6, from a patient with T cell lineage blast crisis of chronic myelogenous leukemia (CML) complicated by hypercalcemia. A surface marker study showed T cell phenotype, cluster designation (CD)4, CD5 and CD7. Light and electron microscopic examination revealed myeloperoxidase (MPO)-negative, however, ultrastructural examination under certain specific conditions demonstrated that some cells were MPO-positive. The TK-6 cell karyotype carried a t(9;22)(q34;q11) and additional chromosome aberrations, including a deletion of the long arm of chromosome 6 and the abnormality of chromosome 7. Southern blot analysis showed rearrangement of the T cell receptor beta-chain (TCR beta) gene and the major breakpoint cluster region (bcr) gene. Northern blot analysis detected the expression of the parathyroid hormone-related protein (PTHrP) gene, however, the proviral genome of human T cell leukemia virus type I (HTLV-I) was negative. This cell line will provide a valuable resource for the analysis of the relationship between T cell lineage crisis and myeloid differentiation and for the analysis of humoral hypercalcemia of malignancy (HHM) or leukemia.
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PMID:Establishment and characterization of a novel cell line, TK-6, derived from T cell blast crisis of chronic myelogenous leukemia, with the secretion of parathyroid hormone-related protein. 747 85

We describe 2 cases of "bilineal" crisis in chronic myelogenous leukemia (CML) with T cell and myeloid phenotypes. In both cases, morphocytochemically distinct myeloid and T lymphoid blast populations proliferated simultaneously in the phase of blastic crisis--myeloperoxidase (MPO)-positive, CD7+/CD33+ myeloblasts in the peripheral blood, and MPO-negative, periodic acid Schiff (PAS)-positive lymphoblasts in the lymph nodes. In each case, common karyotypes containing Ph1 translocation were demonstrated in both the peripheral blood and the lymph node samples. In Case 1, the lymph nodes were occupied by > 90% lymphoblasts, which were positive for CD2, cytoplasmic CD3 (cCD3), CD5 and CD7 and terminal deoxynucleotidyl transferase (TdT), but negative for myeloid antigens. Myeloblasts and T lymphoblasts showed an identical rearrangement of the bcr gene by Southern blotting analysis, although the clonal rearrangement of the T cell receptor (TcR)-delta gene was seen only in T lymphoblasts. In Case 2, simultaneous proliferation of myeloblasts and lymphoblasts was documented morphocytochemically in the lymph node, and a flow cytometric analysis revealed the coexistence of CD7+/CD33+ and CD7+/CD33- blast populations. Each blast population was enriched by antibody-conjugated immunomagnetic beads; the former was positive for MPO by 64% but negative for cCD3 and TdT, whereas the latter was positive for cCD3 and TdT but negative for MPO (< 1%). CD7+/CD33+ myeloblasts and CD7+/CD33- lymphoblasts showed an identical rearrangement of the bcr gene. Neither TcR-beta, TcR-gamma nor the TcR-delta gene was clonally rearranged in either population. These observations clearly indicate that T lymphoid and myeloid blasts share common Ph1-positive progenitors, and that Ph1-positive T lymphoid/myeloid progenitors are probably involved in the development of blastic transformation in some percentage of CML patients.
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PMID:T lymphoid/myeloid bilineal crisis in chronic myelogenous leukemia. 768 98

A patient presented with lymphoblastic lymphoma in lymph-nodes and chronic myelogenous leukemia (CML) in narrow and peripheral blood. All marrow and unstimulated peripheral blood cells contained the Philadelphia chromosome[t(9:22)]. Lymphoma cells were analyzed by flow cytometry and were identified as T cells (CD2+CD5+CD7+CD34+). All fresh lymphoma cells contained the t(9:22) translocation. Cultures of purified peripheral blood T and B cells and specifically stimulated NK cells revealed that 59% of the B cells, 10% of the NK cells, and none of the normal T cells contained the translocation. The lack of translocation in normal peripheral T cells is attributed to their long lifespan. No rearrangement of immunoglobulin or T cell receptor beta or gamma genes was found in either the leukemia or lymphoma cells. Analysis of the DNA from cryopreserved lymphoma biopsy showed clonal rearrangement within the common breakpoint cluster region of the bcr gene identical to the bcr rearrangement in DNA from leukemia blood cells. The data support the concept that T and B cells originate in the patient's totipotent stem cell from which the CML is also derived.
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PMID:Simultaneous demonstration of the Philadelphia chromosome in T, B, and myeloid cells. 768 79

Genes encoding T-cell-receptor alpha/delta chains, neutrophil cathepsin G, and lymphocyte CGL/granzymes are closely linked on chromosomal band 14q11.2. The current work identifies the human mast cell chymase gene (CMA1) as the fourth protease in this cluster and maps the gene to within 150 kb of the cathepsin G gene. The gene order is centromere-T cell receptor alpha/delta-CGL-1/granzyme B-CGL-2/granzyme H-cathepsin G-chymase. Chymase and cathepsin G genes are shown to be cotranscribed in the human mast cell line HMC-1 and in U-937 cells. Other cells transcribe cathepsin G or CGL/granzyme genes, but not chymase genes, suggesting a capacity for independent regulation. Comparison of the 5' flank of the chymase gene with those of cathepsin G and CGL/granzymes reveals little overall homology. Only short regions of the 5' flanks of the human and murine chymase gene sequenced to date are similar, suggesting that they are more distantly related than human and rodent CGL-1/granzyme B, the flanks of which are highly homologous. The expression patterns and clustering of genes provide possible clues to the presence of locus control regions that orchestrate lineage-restricted expression of leukocyte and mast cell proteases.
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PMID:The human mast cell chymase gene (CMA1): mapping to the cathepsin G/granzyme gene cluster and lineage-restricted expression. 846 56


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