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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic myelogenous leukemia (CML) is a human disease associated with a consistent chromosomal translocation that results in sequences from the c-abl locus on chromosome 9 being fused to sequences in a breakpoint cluster region (bcr) on chromosome 22. CML cells have two novel products: an 8.5-kilobase RNA transcript containing both abl and bcr and a 210-kilodalton phosphoprotein (P210) recognized by v-abl-specific antisera. To test whether the P210 is the product of the novel 8.5-kilobase bcr/abl fusion transcript, antibodies were prepared against c-abl and bcr determinants. By using these reagents and v-abl-specific antisera, it was demonstrated that the P210 in CML cells is indeed the protein product of the 8.5-kilobase transcript. By analogy to the gag/abl fusion protein of Abelson murine leukemia virus, the replacement of amino terminal c-abl sequences by bcr sequences in P210 may create a transforming protein involved in CML. A 190-kilodalton phosphoprotein that is a candidate for the normal bcr protein was identified in both HeLa and K562 cells.
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PMID:The chronic myelogenous leukemia-specific P210 protein is the product of the bcr/abl hybrid gene. 346 Jan 76

The cellular abl oncogene and those derived by viral transduction and chromosomal translocation events encode a family of closely related proteins with intrinsic tyrosine kinase activity. The known in vitro and in vivo manifestations of these tyrosine specific kinase activities are, in general, very similar to those of other members of the src gene family. The expression of the normal c-abl messages and gene products is not remarkably different among most tissues, including the haemolymphoid system. However, the broad haemopoietic transformation spectrum of the murine v-abl protein and the association of the abl oncogene with human chronic myelogenous leukaemia suggest that some special structure-function relationship for the abl protein might hold for the growth regulation of blood forming cells. This article concentrates on recent data that have pointed the way toward several testable models for the intracellular behaviour of the c-abl proteins and their altered counterparts which function in cellular transformation and other altered growth states. More detailed review articles which cover the historical development of the field (Baltimore et al, 1979; Rosenberg and Baltimore, 1980), biological properties of the Abelson murine leukaemia virus (Risser, 1982; Whitlock and Witte, 1985) and the structure of the abl gene and its products (Witte, 1983; Konopka and Witte, 1985a) are available.
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PMID:Functions of the abl oncogene. 346 40

An analysis of five patients with Philadelphia chromosome (Ph) negative chronic myeloid leukaemia (CML) revealed that two were clinically and haematologically identical to Ph-positive CML whereas three should be reclassified as chronic myelomonocytic leukaemia (CMML). At a molecular level the first two patients showed the same juxtaposition of c-abl and bcr genes as is seen in Ph-positive CML. These genomic changes were not seen in the other three patients. Observations on these five patients suggest that the clinical course and prognosis of the rare patient who carries the Ph 'molecular defect' but lacks the Philadelphia chromosome is no different from Ph-positive CML.
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PMID:Ph-negative chronic myeloid leukaemia. 347 49

A new hematopoietic cell line derived from a patient with Philadelphia chromosome (Ph1)-negative myeloblastic leukemia arising from a form of myelodysplastic syndrome (MDS) is described. This cell line, designated TMM, consists of immature cells with the morphological characteristics of young myeloblasts and grows in suspension culture with a doubling time of about 30 hours. By cytochemical analysis the cultured cells were positive for acid phosphatase. They were free of the Epstein-Barr virus-associated nuclear antigen as well as terminal deoxynucleotidyl transferase. Further phenotypic analysis revealed the expression of the myelomonocytic-specific antigen Leu-M1 and receptors for the Fc portion of IgG. Partial differentiation of these cells could be induced by dimethyl sulfoxide, tetradecanoyl phorbol acetate, or hypoxanthine and resulted in cells of the myeloid series expressing lysozyme and receptors for the C3b complement protein. The karyotype was 46,XY, lacked the Ph1 chromosome, and displayed no abnormalities at the light microscopic level. No rearrangement of the bcr-c-abl gene complex was found. This cell line should be useful for studying an important type of the heterogeneous population constituting Ph1-negative myeloblastic leukemia, arising in this instance from MDS, as well as for studying differentiation and proliferation of human pluripotent stem cells.
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PMID:Establishment and characterization of a human myeloid cell line from Philadelphia chromosome-negative myeloblastic leukemia arising in a patient with myelodysplastic syndrome. 347 6

The Ph1 chromosome is present in 95% of patients with chronic myelogenous leukaemia (CML). The Ph1 chromosome also occurs in 5-25% of children and adults with acute lymphoblastic leukaemia (ALL). This observation raises questions as to whether these diseases are similar or identical. In patients with CML the c-abl and bcr genes are translocated and abnormally expressed. We studied molecular events related to bcr and c-abl in five patients with ALL to determine its relationship to CML. Four had the Ph1 chromosome; the fifth a probable Ph1 chromosome. c-abl and bcr abnormalities identical to CML were detected in four suggesting a common molecular basis. One patient with the Ph1 chromosome and c-abl translocation lacked these molecular changes but had abnormal c-abl gene transcription apparently unrelated to bcr. These data suggest that Ph1 chromosome positive ALL is heterogeneous; in some patients the molecular abnormality is identical to CML; in others c-abl is likewise involved but via a different mechanism.
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PMID:Multiple molecular abnormalities in Ph1 chromosome positive acute lymphoblastic leukaemia. 347 97

A combination of monosomy 7 and translocation t(9;22) (q34;q11), rarely observed in acute lymphoblastic leukaemia (ALL), is here reported: a peculiarity of this case was that the "breakpoint cluster region" on chromosome 22 was not rearranged, as demonstrated by molecular analysis, and a new c-abl protein (p190) was found, instead of the usual p210 protein usually associated with the Ph chromosome; moreover a rearrangement of c-abl oncogene was found. The clinical course of this patient was, as expected, unfavorable: a few normal metaphases were observed during a short partial remission.
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PMID:Monosomy 7 and Ph-positive acute lymphoblastic leukaemia: cytogenetic and molecular aspects. 348 Apr

Analysis of v-abl-homologous transcripts in peripheral blood leukocytes from 20 leukemia patients revealed a 5-kb species as the major abl-mRNA present. Elevated levels of this 5-kb transcript, together with detectable levels of 2- and 10-kb abl-homologous species, were observed in mRNA samples from two patients, one with Philadelphia chromosome (Ph')-positive chronic myeloid leukemia (CML) in lymphoid blast crisis, and the other with childhood Burkitt-type B-lymphoblastic leukemia. These abl-homologous transcripts differed from the aberrant 8-kb abl-mRNA reported by others in Ph'-positive CML patients in both size and extent of v-abl-homology. No alteration in the organization of v-abl-homologous sequences was detected in the genomic DNA of the Ph'-positive CML patient. Karyotypic analysis of the Burkitt-type B-lymphoblastic leukemia patient revealed the presence of an 8,14 translocation together with a number of other chromosomal aberrations. However, no abnormality of chromosome 9 could be detected. Hence, the observed increase in c-abl transcription is not consistently associated with either gross gene rearrangement or presence of the Ph'. The high levels of c-abl mRNA may be a function of the cell type involved (early lymphoid blast), suggesting that failure to down-regulate c-abl may be a factor in the onset of pre- or early B-lymphoid leukemias.
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PMID:Elevation of c-abl-mRNA in human leukemic B lymphoblasts. 349 35

The structure and the expression of 11 cellular oncogenes (protooncogenes) were analyzed in primary cells from 20 acute lymphocytic (ALL) and 31 acute myelogenous (AML) leukemia patients. Neoplastic cells, obtained prior to initiation of therapy, were purified and classified, on the basis of both surface antigen pattern and morphology, into pre-B, B, and T ALL and M1-M5 AML. RNA was extracted and analyzed for expression of cellular oncogenes coding for nuclear proteins (c-myc, c-myb, c-fos), the beta-chain of platelet-derived growth factor (c-sis), growth factor receptors or related proteins (c-src, c-abl, c-fes, c-erbB), or putative intermediate transducers of mitogenic signals (c-Ha-ras, c-Ki-ras, c-N-ras). Quantitative analysis of total RNA was carried out by dot blot hybridization to specific cDNA or genomic probes. Number and size of transcripts were evaluated by blot hybridization of electrophoretically fractionated poly(A)+ RNA. Expression of c-myc and c-myb was detected in all leukemic cells at variable levels and was characterized by well-defined patterns within ALL subtypes. Conversely, significant levels of c-fos transcripts were detected only in myelomonocytic (M4) and monocytic (M5) leukemias. Among the "src-family," c-fes was expressed more in AML than ALL, and c-abl was expressed at variable but not elevated levels in all leukemia types. c-Ha-ras was uniformly expressed at low levels, as in non-neoplastic cells. c-Ki-ras transcription was detected only in T ALL; N-ras expression was barely demonstrable. The structure of these protooncogenes was not grossly modified, as evaluated by Southern analysis, except for c-myc rearrangement in B ALL. These studies indicate that cellular oncogene expression in specific subtypes of leukemic cells may relate to either the proliferative activity (c-myc, c-myb) or the differentiation state (c-fos) of the cells, or possibly to expression of receptors for putative hemopoiesis-related growth factors (c-fes, c-abl). Our data provide a basis for in-depth analysis of protooncogene expression in normal and neoplastic hemopoiesis.
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PMID:Expression of cellular oncogenes in primary cells from human acute leukemias. 352 May 70

Activation of cellular proto-oncogenes as a result of chromosomal abnormalities has been implicated in the development of some human malignancies. Perhaps one of the most striking examples of this association occurs in chronic myelogenous leukaemia, where the Philadelphia (Ph) translocation results in substitution of the 5' end of the c-abl proto-oncogene with bcr gene sequences. A unique hybrid bcr-abl message is produced. As the Ph translocation is also present in some patients with acute lymphoblastic leukaemia, we initiated studies to determine if similar genomic events occur in these two different forms of Ph-positive leukaemia. Here we report that the Ph translocation in acute lymphoblastic leukaemia can result in production of a novel aberrant c-abl protein that is distinct from the bcr-abl protein found in Ph-positive chronic myelogenous leukaemia. Our observations suggest that alternative mechanisms of activation of c-abl exist, and may be important in the development of human acute lymphoid rather than chronic myeloid malignancies.
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PMID:A novel c-abl protein product in Philadelphia-positive acute lymphoblastic leukaemia. 2838 4

The hallmark of chronic myelocytic leukemia is the presence of the Philadelphia chromosome (Ph1). In recent studies, we obtained data that strongly suggested the involvement of an oncogene, c-abl, in this type of leukemia. This oncogene, normally located on chromosome 9, is translocated to chromosome 22 as a result of the Ph1 translocation. In addition, we identified a region on chromosome 22, the breakpoint cluster region (bcr), which contains the chromosomal breakpoint in all patients with chronic myelocytic leukemia who are positive for Ph1. Recent studies have suggested that the bcr is part of a gene that is truncated as a consequence of the Ph1 translocation. The deleted part of this gene could be replaced by c-abl sequences; to test this hypothesis we analyzed the RNA of five patients with chronic myelocytic leukemia. All five had chimeric bcr/c-abl messenger RNA, suggesting that the deleterious effects of this disease can be associated with an abnormal chimeric protein encoded by the bcr and the c-abl oncogene.
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PMID:Evidence of a new chimeric bcr/c-abl mRNA in patients with chronic myelocytic leukemia and the Philadelphia chromosome. 386 9


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