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Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three patients had complex translocations involving 9q34, 22q11, and a third chromosome (Xq11, 7q11.2, or 15q11.2). Two patients had apparently simple variant Philadelphia (Ph) translocations, t(19;22) and t(11;22), with no obvious involvement of chromosome 9, and the Ph was masked in the t(11;22). In situ hybridization studies showed transposition of the abl gene from chromosome 9q34 to the breakpoint cluster region (bcr) of chromosome 22 in all five patients; this was confirmed by rearrangements of the bcr gene in leukemic DNA. In situ hybridization also showed that the bcr-3' and c-sis probes consistently translocated to recipient chromosomes X, 1, 7, 11, and 15, whereas IgC lambda remained on chromosome 22q. These results confirm that association of abl and bcr is a consistent feature of chronic myeloid leukemia irrespective of the cytogenetic presentation and support the conclusion of Hagemeijer that all simple variant Ph translocations are, in fact, complex and involve at least three chromosomes.
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PMID:A cytogenetic and molecular analysis of five variant Philadelphia translocations in chronic myeloid leukemia. 318 20

The incidence of breakpoints in CML patients with variant translocations was investigated. There was no relationship between the length of various chromosomes with breakpoint frequency. However, a significantly higher (p less than 0.05) incidence of breaks were seen on the long arms as compared to the short arms due mainly to the involvement of 9q and 22q in these translocations. Chromosome 17 showed a significantly (p less than 0.005) higher involvement in these translocations, however only when 9q34-qter was not cytogenetically involved. A total of 683 breaks were found in 225 cases. 362 of these were located at c-abl and c-sis, while 110 were at other oncogenetic sites. The prognostic and hematologic features of patients with variant translocations are not significantly different from those of CML cases with the typical 9q;22q translocation. Some of these complex translocation, where the breakpoints are correlated with oncogenetic sites, are further discussed in molecular terms.
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PMID:Genomic diversity of Philadelphia-positive chronic myelogenous leukemia. 331 28

Chronic myelogenous leukaemia (CML) is a clonal disease arising from malignant transformation of pluripotent hematopoietic stem cells. In most cases, it is characterized by the presence of the Philadelphia (Ph1) chromosome (22q-) which results from a reciprocal translocation between chromosomes 9 and 22 (refs 1-3). In this translocation, the human homologue of the Abelson virus oncogene, c-abl, normally on chromosome 9, is moved to chromosome 22, while c-sis, the cellular homologue of the simian sarcoma virus oncogene, is moved from chromosome 22 to chromosome 9 (refs 4-6). CML cells carrying the t(9;22) chromosomal translocation are known to produce an 8-kilobase (kb) c-abl transcript in addition to the normal 6- and 7-kb transcripts and to express the normal p145 abl protein and a p210 c-abl protein possessing a tyrosine kinase activity not detected in the p145 species. Results of our analyses using somatic cell hybrids between a mouse fibroblast line and two human CML-derived cell lines which carry the Ph1 chromosome and are phenotypically identical to the fibroblast parent indicate that only the hybrid cells containing Ph1 chromosome express both the 8-kb c-abl RNA and the p210 protein. Thus, expression of the altered c-abl transcripts and protein depends on the presence of the Ph1 chromosome and is not myeloid-specific.
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PMID:Expression of a translocated c-abl gene in hybrids of mouse fibroblasts and chronic myelogenous leukaemia cells. 345 50

Cellular oncogenes have been localized at the breakpoints of characteristic chromosomal rearrangements occurring in certain hematologic malignancies. This has been reported to result in aberrant expression of the involved oncogenes. Over 90% of chronic myelogenous leukemia (CML) is characterized by a reciprocal translocation that brings c-abl from chromosome 9 to chromosome 22, and c-sis from chromosome 22 to chromosome 9. To investigate the possible role of these two oncogenes in the leukemic process, we studied their expression in a number of fresh samples obtained from patients with various forms of leukemia, by Northern blot analysis using c-onc probes. Seven of 24 samples obtained from patients with either CML or chronic myelomonocytic leukemia expressed a normal 4.0-kilobase (kb) c-sis transcript. C-sis expression was found only in the accelerated/blast phases but not in the chronic phase of CML. All of the CML Philadelphia chromosome-positive (Ph1+) samples expressed an aberrant 8-kb c-abl transcript. The expression of c-sis in
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PMID:C-sis and C-abl expression in chronic myelogenous leukemia and other hematologic malignancies. 345 50

A patient with chronic myeloid leukemia (CML) presented with an apparently simple Ph translocation t(19;22)(q13;q11). In-situ hybridization revealed movement of the c-abl oncogene from a cytogenetically normal chromosome 9 to the Ph. Bcr-3' and c-sis probes hybridized to distal 1p and not to the 19q+ chromosome as expected from the cytogenetic findings. We concluded that this patient had a complex translocation involving four chromosomes: t(1;9;19;22)(p36;q34;q13;q11).
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PMID:Complexity of an apparently simple variant Ph translocation in chronic myeloid leukemia. 346 84

We and other investigators have previously reported our findings on oncogene expression in human leukemia in an attempt to study the possible involvement of these genes in the leukemic state. An important shortcoming of these studies has been the lack of information on the expression of these genes in normal hematopoietic cells. To address this question we analyzed both the transcript size and level of expression of six oncogenes in fresh hematopoietic cells obtained from hematologically normal individuals and compared the results to those found in fresh samples obtained from patients with various forms of leukemia (acute myelogenous leukemia, acute lymphocytic leukemia, and chronic myelogenous leukemia). We found low level expression of c-myc, c-myb, c-fes, and c-raf in normal bone marrow in sharp contrast to the high levels of expression found in some forms of leukemia. C-fos was highly expressed in both normal bone marrow and certain leukemias. We were unable to detect c-sis expression in our normal samples. With the exception of c-fes, there was no variation in transcript size when comparing normal and leukemic samples. Having defined the transcript sizes and levels of expression for these proto-oncogenes in normal hematopoietic cells, we know that aberrant transcript size for the genes we have studied is not a common event in leukemias. The levels of expression, however, vary widely between normal hematopoietic cells and leukemia as well as between different types of leukemia.
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PMID:Proto-oncogene expression in human normal bone marrow. 366 72

Remarkable chromosome abnormalities were observed in bone marrow cells from a woman with chronic myelocytic leukemia and atypical tuberculosis due to Mycobacterium avium-intracellulare infection. Four chromosome breaks occurred at bands 1p13, 1q32, 11p15, and 22q11. These breaks resulted in a complex Philadelphia (Ph) translocation between chromosomes #1, #11, and #22 and in an inversion of chromosome #1. Oncogenes on these chromosomes include N-ras and c-sk on chromosome #1, c-H-ras on chromosome #11, and c-sis on chromosome #22. Complex chromosome rearrangements may facilitate multiple oncogene changes, thereby permitting several steps in cancer development to occur simultaneously.
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PMID:The Philadelphia (Ph) chromosome in leukemia. III. Complex Ph translocation plus inversion in chronic myelocytic leukemia. 385 75

The CML patients with so called masked Ph1-chromosome have been reviewed. Although the importance of c-sis and c-abl oncogenes is gaining popularity yet their role in the genesis of CML remain obscure. Patients with masked Ph1-chromosomes where chromosome 9 is not involved in the translocation(s) will provide a clue to the role of c-abl and/or c-sis in oncogenesis.
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PMID:"Masked" Ph1-chromosome in chronic myelogenous leukaemia (CML). 385 57

Application of recombinant DNA techniques led to the characterization of a heterogenous group of evolutionary conserved genes with potential transforming activity, called oncogenes. Regularly they seem to be involved in normal cell proliferation and differentiation. Various mechanisms including an increased dosage of gene product as well as subtile point mutations activate these sequences to oncogenes sensu strictu. Molecular analysis of the Philadelphia translocation in leukemic cells of CML-patients revealed a consistent translocation of the human c-abl-oncogene from chromosome 9 to the Ph1-chromosome, regardless of the cytogenetic subtype. Moreover we could demonstrate individual breakpoints for every patient investigated so far. However, these breakpoints are clustered on chromosome 22 within sequences of the bcr-gene. In leukemic cells containing the rearranged-c-abl/bcr sequences a new transcript is detected which is possibly the mRNA for an altered c-abl-protein that unmasks associated tyrosine specific kinase activity. These gene rearrangements were not detected in Ph1-negative CML-patients. Another human oncogene, c-sis, is located on chromosome 22, but seems not to play a crucial role in the generation of CML. These results are discussed in the context of recent advances in oncogene-research.
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PMID:[Philadelphia translocation and the human c-abl oncogene--relations in the light of molecular genetics]. 401 Feb 19

By analysis of a series of somatic cell hybrids derived by fusion of either mouse or Chinese hamster cells with leukocytes from different chronic myelocytic leukemia (CML) patients or from normal donors, we have localized the human oncogene, c-sis, on the q11 to qter segment of chromosome 22 and demonstrated its translocation from chromosome 22 to chromosome 9 (q34) in CML.
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PMID:c-sis is translocated from chromosome 22 to chromosome 9 in chronic myelocytic leukemia. 630 34


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