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

Leukemias induced with the v-abl or BCR/ABL oncogene undergo a process of tumor progression which suggests that the ABL oncogene is required but not sufficient for full transformation. In order to identify cellular changes that correlate with progression to full transformation in v-abl transformed lymphoblasts Abelson virus (A-MuLV)-infected murine bone marrow was plated over a pre-established stromal feeder layer. Shortly after A-MuLV infection, transformed lymphoblasts were poorly oncogenic, but over time, progressed in a stepwide manner to a more oncogenic state. The transformants first acquired the ability to grow efficiently in agar, but only over the feeder layer. They next progressed to efficient feeder-independent growth in liquid culture, and then to efficient feeder-independent growth in soft agar. Cell lines that reached the advanced stage of feeder-independent agar growth showed increased detection by antiphosphotyrosine Western blot of the GAP-associated p62 phosphoprotein as well as of a 55 kDa phosphoprotein while detection of the P160 v-abl phosphoprotein remained constant throughout all stages of progression. Although the identity of the p55 phosphoprotein and the mechanism by which detection of p55 and p62 phosphoproteins change on the Western blots during tumor progression are unknown, the data demonstrate that these changes strongly correlate with the stage of progression of v-abl-transformed cells and raise the possibility that these changes may play a role in tumor progression in this model.
Leukemia 1995 Jan
PMID:Increased detection of specific tyrosine phosphoproteins correlates with tumor progression of Abelson virus-infected lymphocytes. 784 13

The role of BCR gene sequences in Philadelphia (Ph) chromosome-positive leukemia is not well understood. Our previous studies demonstrated that P210 BCR-ABL co-precipitates with P160 BCR following immunoprecipitation with antibodies to the C-terminal domain of P160 BCR, sequences lacking in P210 BCR-ABL. We now report that tryptic peptides shared by both P160 BCR and P210 BCR-ABL are phosphorylated on tyrosine in vitro either when using immune complexes containing P160 BCR complexed to BCR-ABL or when P160 BCR is phosphorylated in trans by P210 BCR-ABL immune complexes from cells lacking functional P160 BCR. P185 BCR-ABL produced in a cell line derived from a Ph chromosome-positive acute lymphocytic leukemia patient also co-immunoprecipitated with P160 BCR. As with P210 BCR-ABL, P160 BCR tyrosine phosphopeptides were shared with P185 BCR-ABL, indicating that the major sites of tyrosine phosphorylation in vitro are contained within the first exon of P160 BCR. Similarly, BCR-ABL autophosphorylation was found to occur predominantly at tyrosines within BCR exon 1 sequences. These results raise the possibility that the activated ABL protein kinase of BCR-ABL proteins modulates the putative signal transduction activities of P160 BCR by tyrosine phosphorylation of exon 1 sequences.
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PMID:BCR-ABL tyrosine kinase is autophosphorylated or transphosphorylates P160 BCR on tyrosine predominantly within the first BCR exon. 842 87

The genome of Abelson murine leukemia virus (A-MuLV) consists of sequences derived from both BALB/c mouse deoxyribonucleic acid and the genome of Moloney murine leukemia virus. Using deoxyribonucleic acid linear intermediates as a source of retroviral deoxyribonucleic acid, we isolated a recombinant plasmid which contained 1.9 kilobases of the 3.5-kilobase mouse-derived sequences found in A-MuLV (A-MuLV-specific sequences). We used this clone, designated pSA-17, as a probe restriction enzyme and Southern blot analyses to examine the arrangement of homologous sequences in BALB/c deoxyribonucleic acid (endogenous Abelson sequences). The endogenous Abelson sequences within the mouse genome were interrupted by noncoding regions, suggesting that a rearrangement of the cell sequences was required to produce the sequence found in the virus. Endogenous Abelson sequences were arranged similarly in mice that were susceptible to A-MuLV tumors and in mice that were resistant to A-MuLV tumors. An examination of three BALB/c plasmacytomas and a BALB/c early B-cell tumor likewise revealed no alteration in the arrangement of the endogenous Abelson sequences. Homology to pSA-17 was also observed in deoxyribonucleic acids prepared from rat, hamster, chicken, and human cells. An isolate of A-MuLV which encoded a 160,000-dalton transforming protein (P160) contained 700 more base pairs of mouse sequences than the standard A-MuLV isolate, which encoded a 120,000-dalton transforming protein (P120).
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PMID:Characterization of mouse cellular deoxyribonucleic acid homologous to Abelson murine leukemia virus-specific sequences. 927 86

The abi-1 gene encodes a protein that binds and is phosphorylated by the Abelson protein tyrosine kinase. Constructs expressing a full-length abi-1 cDNA, and a smaller cDNA arising from an alternatively spliced form, were generated and tested for their effect on transformation of NIH3T3 cells by the Abelson murine leukemia virus. Overexpression of both forms of the protein strongly inhibited transformation by the wild-type P160 strain of the virus, but not by the non-interacting mutant P90A strain. The inhibition required the SH3 domain of Abi-1, suggesting that a direct interaction was required for the effect. Rare breakthrough P160 transformants of the Abi-1 overexpressing lines were found to have downregulated Abi-1 protein levels by a post-transcriptional mechanism.
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PMID:Inhibition of v-Abl transformation in 3T3 cells overexpressing different forms of the Abelson interactor protein Abi-1. 1152 77


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