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

Chromosomal translocation within B and T cell malignancies has proven a rich source for proto-oncogenes. The obligate DNA breaks within immunoglobulin (Ig) and T cell receptor (TCR) loci are frequently the sites of recurrent translocations. Burkitt's lymphoma established the paradigm by introducing the myc oncogene from chromosome segment 8q24 into the Ig heavy chain gene locus at 14q32. Molecular cloning of an aberrant Ig rearrangement in follicular lymphoma revealed Bcl-2. Bcl-2 constitutes the first member of a new category of oncogenes: regulators of programmed cell death. Bcl-2 blocks apoptosis and maintains long-term immune responsiveness including B-cell memory. The PRAD1 gene of parathyroid adenomas appears to be the elusive Bcl-1 gene of t(11;14)(q13;q32) bearing lymphomas. It proves to be a novel G1 cyclin. Acute lymphoblastic leukemias (ALL) pre-B phenotype produce a E2A/PBX fusion protein that possesses the leucine zipper of E2A with the homeodomain of PBX. Two molecular forms of the BCR/ABL fusion protein are produced by the Philadelphia chromosome. A deregulated p210 tyrosine kinase is found in chronic myelogenous leukemia, while a p190 form predominates in Ph+ ALL. In contrast, T-cell ALLs introduce a potpourri of genes into their T cell receptor loci. However, a common theme is emerging. These oncogenes (Ttg1, Ttg2, SCL, LylI, H0X11) all belong to classic families of transcription factors, possessing LIM domains, helix-loop-helix motifs, or homeodomains. Provocatively, these transcription factors are normally intended for lineages other than T cells. These genes have widened the horizons of both oncogenesis and normal development.
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PMID:Chromosomal translocations in lymphoid malignancies reveal novel proto-oncogenes. 159 Oct 3

The pattern of immunoglobulin (Ig) and T cell receptor (TCR) gene rearrangements was determined in 87 patients with acute and chronic leukaemias and myelodysplastic syndromes by Southern blot hybridisation. All 31 cases of common, B cell and null cell acute lymphoblastic leukaemia, and B cell chronic lymphocytic leukaemia showed Ig heavy chain (JH) rearrangement, and TCR (beta-chain) rearrangement was seen in all 5 cases of T cell acute lymphoblastic leukaemia. Inappropriate JH and TCR (beta) rearrangements were present in some cases of T-ALL (60%) and common acute lymphoblastic leukaemia (18%), respectively. For the 19 patients with acute leukaemias following chronic myeloid leukaemia, blastic transformation, all 4 with lymphoid transformation and 3 of the 15 with myeloid transformation had JH rearrangement, and 3 CD10-positive lymphoid transformation and 2 myeloid transformation had their TCR (beta) genes rearranged. In conclusion, the pattern of Ig and TCR gene rearrangements correlated well with the cell lineage. However, cross-lineage rearrangements were more commonly seen in patients with acute leukaemias following chronic myeloid leukaemia blastic transformation, as compared to the de novo cases.
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PMID:Rearrangement of immunoglobulin and T cell receptor genes in acute and chronic leukaemias. 185 Sep 43

The authors investigated cytoplasmic immunoglobulins of the leukemic cells from 20 adult cases with non-T-cell acute lymphocytic leukemia (ALL) and from three cases with chronic myelogenous leukemia in lymphoid blast crisis using immunoelectron microscopy. They also studied these cases using various monoclonal antibodies. Of the 23 examined cases, nine were negative for both heavy and light chains of immunoglobulins; the authors defined these as common ALL. Two cases were positive for the mu chain but were negative for light chains; the authors defined these as pre-B-cell ALL. The remaining 12 cases were positive for either kappa or lambda light chains; these were defined as B-cell ALL. Of the 12 cases positive for light chains, 11 were positive for the lambda chain. Seven cases of the 11 positive cases for the lambda chain were negative for heavy chains. Eleven cases were positive either for both My4 and My9 or for one of the two antibodies. From these results, the authors conclude the following: (1) the ratio of pre-B-cell ALL among non-T-cell ALL cases (two of 23 cases) was lower in adults than in children; (2) of the light chain-positive cases, the lambda light chain-positive cases predominated (11 of 12 cases); (3) heavy chain-negative, lambda chain-positive cases (seven cases) were observed; and (4) one half of the leukemia cases showed dual phenotypes of B-cell and myeloid cell lineages.
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PMID:Predominant expression of lambda light chain in adult cases with non-T-cell acute lymphocytic and chronic myelogenous leukemia in lymphoid blast crisis. 190 73

Cytofluorographic analysis of surface immunoglobulin (sIg) light chain clonal excess (CE), defined as (%kappa+ - %lambda+)/(%kappa+ + %lambda+) cells per discrete level of fluorescence intensity, was carried out on mononuclear cells of 32 leukemic patients. Eight demonstrated sIg light chain CE, including four blastic chronic myeloid leukemias (BL-CML), three "null" acute lymphoblastic leukemias (ALL), and one leukemic lymphoblastic lymphoma. Six of the leukemias demonstrated a kappa CE and two had a lambda CE. Sorted kappa+ PB cells from a BL-CML patient were shown to have a diploid DNA stem line and to bear the "common" ALL antigen. To provide further support for our finding of the expression of sIg light chains in ALL, we studied the REH cell line, derived from a "common" ALL patient and found cytoplasmic mu heavy chain and surface Ig lambda CE. Nucleic acid blotting experiments on REH revealed that both kappa genes had been deleted and that lambda genes had been rearranged, as expected in B cells expressing lambda light chains. Moreover, REH cells contained mu and lambda RNA. When REH cells were treated with TPA the amount of mu chain RNA increased by approximately fivefold and the amount of lambda chain RNA increased by approximately twofold. The finding of sIg light chain in pre-B cell leukemias and in the REH cell line, suggests that these leukemic cells are further differentiated along the B-cell lineage than was previously believed.
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PMID:Surface immunoglobulin light chain expression in pre-B cell leukemias. 242 86

Recombinant tumor necrosis factor (rTNF) and rIFN-gamma induce in the human leukemia cell lines HL-60, ML3, and U937 the accumulation of transcripts of the X chromosome-linked chronic granulomatous disease (X-CGD) gene, encoding the 91-kD heavy chain of cytochrome b-245, a component of the NADPH oxidase of phagocytic cells. The gene is induced within 6 h by either cytokine, and its accumulation is observed upon induction with rIFN-gamma up to 5 d. The combined effect of the two cytokines is more than additive. rIFN-gamma also induces accumulation of X-CGD mRNA in immature myeloid cells from peripheral blood of chronic myeloid leukemia (CML) patients, whereas rTNF has almost no effect. The cells from CML patients constitutively express TNF mRNA, suggesting that endogenously produced TNF may play a role in the effect of rIFN-gamma on these cells. rTNF induces X-CGD gene expression in the myeloid cell lines acting, at least in part, at the transcriptional level, as shown in nuclear run-on experiments. The gene encoding the 22-kD light chain of cytochrome b-245 is constitutively expressed in the human myeloid cell lines and the accumulation of its transcripts is affected by neither rTNF nor rIFN-gamma, rTNF and rIFN-gamma synergistically to induce the cell lines to express the cytochrome b-245 heterodimer (as evaluated by its visible spectrum), and to produce NADPH oxidase activity and H2O2 upon stimulation with phorbol diesters.
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PMID:Tumor necrosis factor and immune interferon synergistically induce cytochrome b-245 heavy-chain gene expression and nicotinamide-adenine dinucleotide phosphate hydrogenase oxidase in human leukemic myeloid cells. 249 43

We have determined the arrangement and expression of immunoglobulin (Ig) and beta-T-cell receptor (TCR) genes in six established Philadelphia chromosome-positive (Ph1) chronic myelogenous leukemia (CML) cell lines, and correlated these results with their phenotypic characteristics. Three cell lines with nonlymphoid characteristics, EM2, EM3, and K562, did not demonstrate rearrangement or expression of Ig or beta-TCR genes. A new cell line, MB, with a mature B-cell phenotype recently established in our laboratory, contained light and heavy chain immunoglobulin gene rearrangements and expressed mature Ig RNA. In a cell line with an early lymphoid phenotype, BV173, this analysis showed rearrangement of Ig heavy chain and beta-TCR genes, unrearranged Ig light chain DNA, and expression of only an immature beta-TCR transcript. This line provides evidence for T-cell lineage involvement in Ph1 CML. One cell line without markers of any cell type, KCL-22, demonstrated rearranged, unexpressed Ig heavy chain genes, suggesting these cells are at the very earliest stages of lymphoid differentiation. These lines should provide valuable tools to dissect the molecular biology of differentiation in CML and in early lymphocytes.
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PMID:Rearrangement and expression of beta-T-cell receptor and immunoglobulin genes in established Ph1 chronic myelogenous leukemia cell lines. 255 59

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

Class I antigens were isolated by immunoprecipitation from cell extracts prepared from mitogenically stimulated and internally radiolabeled peripheral blood lymphocytes (PLBs). The precipitating antibodies used are monomorphic and recognize a determinant on the heavy chain of HLA-A, B, C antigens regardless of their allelic specificities when complexed with beta 2m, or determinants on beta 2m itself. Comparison of class I molecules isolated from 25 different homozygous typing cells (HTC) and analyzed by two-dimensional (2-D) gel electrophoresis allowed the identification of those HLA-A, B locus specificities most common in the European Caucasoid population. Class I antigens isolated from HTC that are HLA identical are biochemically indistinguishable also. Evidence was obtained for the expression of additional class I antigens besides the HLA-A, B, C locus products: for some haplotypes, up to six class I genes may be active in mitogenically activated PBLs.No differences in molecular weight and isoelectric point of the class I heavy chains were observed between the antigens recognized by W6/32, the anti-heavy chain reagent, and anti beta 2m reagents. The nature of the mitogenic stimulus, i.e., pokeweed mitogen or phytohemagglutinin, was irrelevant with respect to the class I antigens isolated by this method. Using the HTCs as reference, a panel of HLA-B27 positive heterozygous cells was analyzed. Two types of HLA-B27 antigens, distinct by CML typing were represented. These two forms differed also in their biochemical properties. In addition, we obtained evidence for the existence of an A2 variant. This finding was likewise confirmed by CML typing.
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PMID:Analysis of human class I antigens by two-dimensional gel electrophoresis. I. Polymorphism, evidence for additional (non-HLA-A, B, C) gene products, and identification of variant HLA-A, B antigens. 618 77

IgG heavy chain constant region allotypes, Gm, the genetic marker of human chromosome 14q32, are markers for susceptibility to certain diseases. We tested Gm allotypes in 365 patients with various types of haematological malignancies, 528 healthy controls and 35 healthy HTLV carriers. The frequency of specific Gm phenotypes was significantly increased in patients with adult onset null-ALL, AML, AMoL and CML in blastic crisis. Among these diseases, the frequency of Gm1,2,21 haplotype was significantly increased with adult onset null-ALL, AML and AMoL.
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PMID:IgG heavy chain allotype (Gm), a genetic marker for human chromosome 14q32, and haematopoietic malignancies. 643 Jun 11

We have investigated the configuration of immunoglobulin (Ig) genes in leukaemic cells in 17 patients with B-cell leukaemias (11 chronic lymphocytic leukaemias (B-CLL); 4 prolymphocytic leukaemias (B-PLL), and two hairy cell leukaemias (HCL)). In addition we studied four patients with T chronic lymphocytic leukaemia (T-CLL); four patients with acute leukaemia (3 acute lymphoblastic leukaemias (ALL), and 1 mixed acute leukaemia (M.AL)); and six patients with chronic granulocytic leukaemias in blastic crisis (CGL.BC). The heavy chain genes (H) were analysed by using probes for the constant region of the mu chains (C mu) and for the joining region (JH). The light chain genes were analysed by using probes for the constant region of the kappa (C kappa) and lambda (C lambda) chains. We have found rearranged Ig genes in all cases of B-CLL, B-PLL and HCL, but in none of the patients with T-CLL. In one case of HCL, both mu genes were deleted, indicating that in this case the class switch has taken place. In four out of six cases with either ALL or lymphoid CGL.BC and in one case of M.AL, an Ig gene rearrangement was also found. No rearrangement was detected in two cases of myeloid CGL.BC. When the combination of rearrangement versus germ-line configuration was considered, a variety of patterns emerge, but in no case did we find a L chain gene rearranged without at least one H chain gene being rearranged as well. Whereas in the majority of cases of B-CLL only one H chain gene is rearranged, in nearly all cases of B-PLL both H chain genes are rearranged. By systematic analysis of restriction fragment sizes of rearranged genes, we have established that a large number of different variable regions for the H chain (VH) are involved in Ig gene rearrangement in B-cell malignancies. Our data confirm that testing for Ig gene rearrangement may be the most sensitive and specific test for identifying leukaemic cells of B lineage.
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PMID:DNA rearrangements of immunoglobulin genes correlate with phenotypic markers in B-cell malignancies. 643 75


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