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

Structural alterations of the oncogenes in human tumors are reported to result from a variety of mechanisms: point mutations, chromosomal translocations and gene amplifications. In over 90% of the cases of chronic myelogenous leukemia (CML), the c-abl oncogene is translocated from chromosome 9 to chromosome 22, and forms in part the Philadelphia (Ph1) chromosome. We have molecularly analysed a double Ph1-positive (Ph1+) cell line, KBM-5 that was established from a patient with CML in the blast-transformed phase (CML-BP). We report that the c-abl, bcr, and C lambda genes are amplified approximately eight-fold in the cell line but not in the fresh uncultured cells from which KBM-5 was derived.
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PMID:The c-abl, bcr and C lambda genes are amplified in a cell line but not in the uncultured cells from a patient with chronic myelogenous leukemia. 309 97

The major consequence of the formation of the Philadelphia (Ph1) chromosome characteristic of leukemia cells of patients with chronic myelogenous leukemia (CML) is fusion of c-abl and bcr genes. Using a sensitive RNase protection technique, we analyzed mRNA from a large number of CML patients. In most, we identified one or both species of bcr-abl chimeric transcripts. These two mRNAs vary in the specific bcr exon joined to abl exon II and are translated into slightly different proteins. The amounts of the fused mRNA within leukemia cells vary considerably between individuals and do not correlate with the phase of the disease.
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PMID:bcr-abl RNA in patients with chronic myelogenous leukemia. 310 69

A new Philadelphia chromosome (Ph1)-positive cell line, designated TOM-1, was derived from bone marrow cells of a patient with Ph1-positive acute lymphocytic leukemia (ALL). The TOM-1 cells were positive for Ia and B1 antigens and terminal deoxynucleotidyl transferase (TdT) but negative for common ALL antigen. Although neither surface Ig nor cytoplasmic Ig was detected, the TOM-1 cells contained rearranged immunoglobulin-H chain genes but retained germ-line kappa chain and germ-line T cell receptor beta-chain genes. These results indicate that the TOM-1 cells reside as the progenitor of pre-B cells. We have investigated the chromosome 22 breakpoint and c-abl gene expression in the TOM-1 cells. We found that the breakpoint on chromosome 22 was within the breakpoint cluster region (bcr) in the TOM-1 cells. We also found the breakpoints within or near bcr in four of six Ph1-positive ALL cases, similar to the findings in Ph1-positive CML cases. Amplification of the c-abl gene was not detected in the TOM-1 cells. The leukemic cells isolated from a patient with CML in myeloid crisis contained a novel 8-kilobase (kb) abl-related messenger RNA (mRNA), but the TOM-1 cells contained c-abl transcripts of only normal sizes, despite the fact that they showed the bcr gene rearrangement.
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PMID:Establishment and characterization of a cell line, TOM-1, derived from a patient with Philadelphia chromosome-positive acute lymphocytic leukemia. 310 21

The hallmark of human chronic myeloid leukaemia is a 9;22 chromosome translocation that fuses most of the c-abl oncogene to the 5' portion of the breakpoint cluster region (bcr) gene, such that a hybrid bcr-abl mRNA and polypeptide are generated. To clarify further the nature of this translocation, we have analysed the structure of normal human bcr mRNA by isolating large cDNA clones that collectively span the entire coding region and extend 2.6 kb upstream of those previously described. The 3150-bp nucleotide sequence reported here includes 534 bp of a GC-rich 5' non-coding segment and indicates, in conjunction with published sequences, that the bcr polypeptide comprises 1271 amino acid residues. The predicted polypeptide is unrelated to serine or tyrosine kinases, or indeed to any previously published sequence; its structure provides no evidence of a transmembrane region. Since probes from throughout the 4.8-kb cloned region hybridized to both the 4.5 and 6.7 kb normal bcr transcripts, both RNAs contain most or all of that region.
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PMID:cDNA sequence for human bcr, the gene that translocates to the abl oncogene in chronic myeloid leukaemia. 310 80

The expression of c-abl, c-sis, c-myc and N-ras oncogenes was examined in 2 lymphoblastoid cell lines, one with Ph1 (PB-1049) and the other without Ph1 (LN-1049), both established from a patient with chronic myelogenous leukemia (CML), and in a Ph1-positive cell line (PB-1049-T) derived from a tumor formed after transplantation of PB-1049 cells in a nude mouse with reference to their tumorigenic potential in nude mice. The normal transcripts of c-abl were detected in all 3 lymphoblastoid cell lines. Although in situ hybridization of v-abl proved, and restriction endonuclease analyses of the bcr region strongly indicated the occurrence of bcr-abl rearrangement in PB-1049 and PB-1049-T, we could not obtain any evidence for the expression of the hybrid bcr-abl mRNA. These results indicate that the Ph1 translocation does not ensure the production of the hybrid bcr-abl mRNA, and that the expression of hybrid bcr-abl gene is not essential for the maintenance of tumorigenicity of these cell lines. Expression of c-sis was not detected in any of the cell lines examined, whereas the expression of c-myc was uniformly higher in the 3 cell lines than in normal control cells. The levels of N-ras expression varied considerably, probably in parallel with the changes in tumorigenicity of the cell lines. N-ras expression in the PB-1049 and PB-1049-T cell lines was higher than that in the LN-1049 line when they retained tumorigenic potential, but it fell to the level of LN-1049 with loss or decline of tumorigenicity.
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PMID:Absence of the hybrid bcr-abl mRNA in Ph1-positive B lymphoblastoid cell lines established from a patient with chronic myelogenous leukemia. 312 21

The reciprocal translocation between human chromosomes 9 and 22, termed the Philadelphia chromosome (Ph1), is observed in more than 90% of patients with chronic myelogenous leukemia. This translocation fuses sequences from a variable distance 5' to the c-abl locus on chromosome 9 to sequences in a breakpoint cluster region (bcr) on chromosome 22. The appearance of the Ph1 chromosome is correlated with the production of a novel 8.7-kb RNA transcript containing both bcr and c-abl sequences as well as with a 210-kd phosphoprotein (p210c-abl) representing non-abl polypeptide sequences fused to c-abl-derived sequences. Antibodies prepared to a number of different c-abl domains and to bcr determinants were employed to characterize the normal and altered c-abl gene products. By combining a variety of cDNA cloning techniques, we have isolated bcr/abl clones representing 8.7 kb of contiguous mRNA sequence.
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PMID:Molecular cloning and serological characterization of an altered c-abl gene product produced in Ph1 CML patients. 312 80

Leukemic cells from patients with Philadelphia chromosome (Ph1)-positive chronic myelogenous leukemia (CML) contain a 210 kDa protein (P210bcr-abl) with a protein tyrosine kinase activity that is a product of fused bcr and abl genes. We have prepared two monoclonal anti-peptide antibodies, one from each gene product, and have affinity purified each. Incubation of anti-abl (c-abl 51-64) immunoprecipitates of K562 cells with [gamma-32P]ATP in protein kinase assays resulted in the labeling of P210bcr-abl and a 53 kDa (ph-P53) protein. Increasing concentrations of antibody detected similar ratios of P210bcr-abl: ph-P53, suggesting the presence of a complex between the proteins. Several different anti-abl and anti-bcr antibodies detected the ph-P53/P210 complex. Sodium dodecyl sulfate (SDS) treatment without 2-mercaptoethanol eluted P210bcr-abl and ph-P53 from the monoclonal antibody in the form of complexes which migrated on 6% SDS-polyacrylamide gels and had apparent molecular weights of 275,000 and more than 500,000. Both complexes yielded ph-P53 and P210bcr-abl upon treatment with SDS-mercaptoethanol. Studies involving glycerol gradient centrifugation also detected complexes of P210bcr-abl and ph-P53. Our results indicate that ph-P53 is not a degraded product of P210bcr-abl, does not share antigenic determinants with P210bcr-abl since it is not recognized by anti-abl and bcr antibodies in immunoblots, is not the phosphorylated heavy chain of immunoglobulin G, and is different from p53 (the nonviral T protein) complexed to the large T antigen of simian virus 40. Previous studies (Maxwell et al., 1987) have shown that ph-P53 has a different peptide map than P210bcr-abl. Therefore, we conclude that ph-P53 is a distinct cellular protein complexed to P210bcr-abl in K562 cells.
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PMID:A novel 53 kDa protein complexed with P210bcr-abl in human chronic myelogenous leukemia cells. 313 27

Activation of the oncogenic potential of c-abl proto-oncogene has been correlated with the activation of its tyrosine kinase activity. The oncogenes derived from c-abl, e.g., gag/v-abl in Abelson murine leukemia virus or bcr/abl in chronic myelogenous leukemia, lack N-terminal coding sequences of the normal c-abl gene. In mouse and human cells, two sets of N-terminal amino acids encoded by 5'-variable exons are found in c-abl proteins. To assess the importance of N-terminal deletion in the activation of c-abl tyrosine kinase, a full length or an N-terminal deleted c-abl protein was expressed in bacteria and in monkey COS cells. Measurements of the autokinase activity of these two c-abl proteins showed that deletion of the N-terminal amino acids led to a three to five fold increase of the c-abl tyrosine kinase activity. Thus, the N-terminal deletion is important in the activation of c-abl proto-oncogene.
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PMID:Negative regulation of c-abl tyrosine kinase by its variable N-terminal amino acids. 314 98

In chronic myeloid leukemia (CML), a chromosome translocation has fused the bcr gene to the c-abl oncogene, such that a chimeric bcr-abl polypeptide can be made. To explore the biological properties of bcr-abl and compare them with those of the Abelson virus (AMuLV) transforming gene (gag-v-abl), we have used either a synthetic bcr-v-abl gene that mimics the translocation product or, in some experiments, a bcr-c-abl cDNA. A new retroviral vector was used to introduce the genes into the factor-dependent myeloid line FDC-P1. Both bcr-abl and v-abl efficiently rendered the myeloid cells factor independent and tumorigenic. Their fully autonomous growth may be due to the myeloid growth factor interleukin-3 (IL-3) made in small amounts by the infected cells. Hence autocrine factor production may feature in CML development and Abelson virus transformation.
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PMID:bcr-abl oncogene renders myeloid cell line factor independent: potential autocrine mechanism in chronic myeloid leukemia. 314 34

A female with chronic myelocytic leukemia (CML) in blastic phase (BP) showed a masked Ph chromosome that had originated by a translocation between chromosomes 8 and 22, with no obvious involvement of chromosome 9. A duplication of the masked Ph and trisomy 13 were present as additional anomalies. The karyotype on peripheral blood unstimulated cultures was 48,XX,t(8;22)(p12;q11),+13,+der(22) t(8;22)/47,XX,t(8;22)(p12;q11),+der(22)t(8;22). While the duplication of the Ph is a frequent finding in BP of CML, we did not find any other case in the literature with duplication of a masked Ph. In situ hybridization with c-abl and bcr probes showed that a 3' bcr sequence was translocated to the der(8) chromosome, while the c-abl oncogene was transposed to the masked Ph.
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PMID:Transposition of c-abl oncogene in a case of masked Ph chromosome duplicated in blastic phase. 316 25


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