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

Rearrangements of immunoglobulin and T cell receptor (TCR) genes have been demonstrated in malignant lymphoid tumors of B and T cell origin. In Philadelphia chromosome-positive chronic myeloid leukemia and acute lymphocytic leukemia cells the bcr and c-abl genes are reorganized and transcripts composed of both genes are expressed. We analyzed the organization of bcr, immunoglobulin and TCR genes in malignant lymphomas. Our data show that in all B cell lymphomas analyzed the JH genes and in some cases also the J kappa genes were rearranged. In a Burkitt lymphoma and in a Kil lymphoma distinct rearranged TCR gamma fragments were detected, in a second Burkitt lymphoma two rearranged TCR beta gene fragments occurred together with a rearranged JH gene fragment. In two T cell lymphomas rearranged TCR beta genes were observed; one of these lymphomas also carried rearranged TCR gamma and JH genes. In Hodgkin's disease in 3 out of 7 cases rearranged immunoglobulin genes were detected. In 1 case, which was diagnosed as a follicular hyperplasia, rearranged JH and TCR gamma fragments appeared. In none of the analyzed lymphomas could bcr rearrangements be observed.
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PMID:Analysis of immunoglobulin, T cell receptor and bcr rearrangements in human malignant lymphoma and Hodgkin's disease. 216 Jun 31

Cytogenetic analysis for an atypical case of chronic myeloid leukemia (CML) showed a complex karyotype with four chromosome breakpoints (5q12, 12q21, 12q24, and 22q11) and translocation products that included a typical Philadelphia chromosome but apparently normal chromosomes 9. Molecular genetic analyses using four breakpoint cluster region (bcr) probes indicated that three breaks were probably present on chromosome 22. Two apparently independent breaks appeared to exist within the bcr, one of which was probably associated with a deletion of some bcr sequences. By combining the molecular and cytogenetic data, we could infer a total of seven breaks. This case illustrates the extensive and complex types of genetic alteration that may be associated with a c-abl and bcr fusion.
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PMID:Highly complex genetic rearrangement involving at least seven breakpoints in a case of chronic myeloid leukemia. 216 79

A novel erythroid cell line, RM10, was established from a long-term bone marrow culture of a patient with chronic myelogenous leukemia (CML). RM10 cells were positive for periodic acid Schiff (PAS), but negative for peroxidase and dual esterase. RM10 cells had la, pre B (CD10), myeloid (CD13, CD14, CD33) and erythroid (glycophorin A) markers, but had no other lymphoid, megakaryocytic, or mesenchymal cell markers. RM10 cells spontaneously synthesized hemoglobin, which was markedly enhanced with hemin. Isoelectric focusing of the cell lysates and northern blot analysis of the total cellular RNA revealed hemoglobin synthesis in the cells. Using 125I-labeled recombinant human erythropoietin (Epo), two classes of Epo receptors were demonstrated in the RM10 cells. However, Epo did affect neither growth nor erythroid differentiation of the cells. RM10 cells rapidly differentiated to monocytic cells in the presence of 12-0-tetradecanoylphorbol-13-acetate, and simultaneously expressed glycoprotein IIb/IIIa. RM10 cells had Philadelphia chromosome (Ph), and expressed p210bcr-abl using immunoprecipitation with anti-c-abl and anti-phosphotyrosine antibodies. These results indicate that the RM10 cells have the characteristics of multipotential hemopoietic cells originating from Ph-positive CML and that high affinity Epo receptor class is not a sufficient condition for Epo responsiveness.
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PMID:A novel CD10-positive erythroid cell line, RM10, established from a patient with chronic myelogenous leukemia. 216 10

The Philadelphia (Ph1) chromosome is found in the majority of patients affected by chronic myelogenous leukemia (CML), being considered the hallmark of the disease, but around 5-8% of patients diagnosed as CML lack the Ph1 chromosome-negative (Ph-) CML has been discussed extensively in the literature because of its heterogeneity. However, it is now accepted that some of the Ph1-CML patients have a disease indistinguishable from Ph1-positive (Ph+) CML. It was investigated whether Ph- CML with clinical and morphological features indicating true CML would always have bcr rearrangements, as the relocation of c-abl from 9q34 into the breakpoint cluster region on 22q11 is considered a crucial event in the pathogenesis of CML. From molecular studies, it seemed that Ph- CML with features of true CML always have the bcr rearrangement, while Ph- patients, lacking such rearrangement, have atypical forms of CML. Here we describe 8 Ph- CML and myeloproliferative syndrome (MPS) patients of whom 6 were by all respects true CML cases. Nevertheless, bcr rearrangement and expression of the classic bcr/abl chimeric mRNA was found in only 1 of the 6 patients. More advanced molecular techniques will be needed to understand which molecular mechanisms underlie Ph-, bcr- CML, resulting in phenotypes sometimes indistinguishable from Ph+, bcr+ CML.
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PMID:Chronic myelogenous leukemia with typical clinical and morphological features can be Philadelphia chromosome negative and "bcr negative". 219 65

Strong evidence implicates fusion of control elements and 5' sequences of the bcr gene of chromosome 22 with 3' sequences of the c-abl gene of chromosome 9 in the pathogenesis of Ph-positive and certain cases of Ph-negative chronic myelogenous leukemia (CML). Since this fusion gene gives rise to a chimeric tyrosine protein kinase with transforming potential, and since the bcr exon contribution to this chimeric protein is variable, the question has arisen as to whether bcr breakpoint location and bcr exon contribution could influence the clinical course of CML. Prior studies have yielded conflicting results on this point. Here we have looked, in a manner approximating a prospective analysis, at the relation of bcr breakpoint localization to the duration of chronic phase, total survival, and blast crisis phenotype in 81 patients presenting in the chronic phase of CML. We have found no significant differences in chronic phase duration or total survival among patients with breakpoints in the three major subregions of a breakpoint cluster region within the bcr gene. These findings indicate that chronic phase duration and total survival cannot be predicted from bcr breakpoint for CML patients presenting in chronic phase and suggest that unknown oncogenic events determining the onset of blast crisis are the prime determinants of prognosis. Combined analysis of blast crisis cell lineage in our patients and patients presented in a previous study has revealed an overall ratio of myeloid:lymphoid (M:L) crisis of 3.4:1, but a striking predominance of myeloid crisis in patients with breakpoints in subregion 2 (M:L of 9:1), and a lower than expected M:L ratio (1.6:1) among patients with breakpoints in subregion 3 (P for subregion 2 versus 3 = .012; subregions 0,1,2 versus 3 = .012; subregions 0,1,3 versus 2 = .032). The molecular basis for this divergence from the anticipated M:L ratio in patients with breakpoints in bcr subregions 2 and 3 is unknown.
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PMID:Relationship of bcr breakpoint to chronic phase duration, survival, and blast crisis lineage in chronic myelogenous leukemia patients presenting in early chronic phase. 226 56

A "masked" Philadelphia chromosome (Ph), t(1;22;9)(p32;q11;q34), was found in the bone marrow and peripheral blood cells of a patient with chronic myeloid leukemia (CML) during the chronic and blastic phases of the disease. As an additional change, a reciprocal translocation t(12;13)(p13;q14) was observed in the blastic phase. Southern blot analysis showed a rearrangement of the breakpoint cluster region (bcr). Northern blot analysis with a c-abl probe showed an abnormal 8.5 kb c-abl RNA transcript in addition to the normal 6- and 7-kilobase (kb) c-abl species. Thus, the results demonstrate the presence of a c-abl/bcr rearrangement in the masked Ph corresponding to that observed in the standard Ph translocation t(9;22)(q34;q11) of CML.
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PMID:Cytogenetic and molecular analysis of a "masked" Philadelphia chromosome in chronic and blastic phases of chronic myeloid leukemia. 235 96

The Philadelphia (Ph1) chromosome (22q-), found in more than 90% of patients with chronic myeloid leukemia (CML), is one part of a reciprocal translocation, t(9;22) (q34;q11), in which the oncogene c-abl moves from 9q34 to 22q11. The translocation results in the translation of an aberrant abl-related protein with tyrosine kinase activity. Genetically active genes are known to have chromatin which is hypersensitive to deoxyribonuclease I (DNase I) and to be hypomethylated. Using an in situ nick translation technique on metaphase chromosomes, we have examined DNase I sensitivity and methylation status at the breakpoints 9q34 and 22q11 in bone marrow cells from controls (two cases) and CML patients (three cases). In CML cells DNase I sensitivity was significantly increased, at both breakpoints, in the translocated chromosomes compared with their normal homologues in CML cells and with both homologues in control marrows. A hypermethylated site, seen at 22q11 in normal 22s was hypomethylated on 22q-. The 9q34 region was hypomethylated in normal and translocated chromosomes. DNase I sensitivity, seen at 22q13 in CML cells, was lost following translocation in one of three cases. This technique demonstrates alterations in chromatin conformation and methylation status at translocation breakpoints which may be related to acquired genetic activity at one or both of these sites.
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PMID:Possible evidence for acquired genetic activity at both chromosomal breakpoints of the Philadelphia translocation in chronic myeloid leukemia. 238 79

The hallmarks of chronic myelogenous leukemia (CML) include the Philadelphia chromosome (Ph) translocation [t (9;22)(q34;q11)] and consistent molecular genetic aberrations: a break within a restricted 5.8 kb DNA segment, bcr, on chromosome 22q11; transposition of the c-abl protooncogene from chromosome 9q34 to 22q11; and formation of a hybrid bar-abl gene encoding an abnormal 210 Kd bcr-abl protein with augmented tyrosine kinase enzymatic activity. These molecular phenomena may occur even in the absence of cytogenetic evidence of the Ph translocation. They are highly specific and sensitive markers for CML, and are presumed to play a significant role in the pathogenesis of this malignancy. Surprisingly, we have encountered 11 patients who lacked the Ph translocation, bcr rearrangement, and (in the four patients with available mRNA) a bcr-abl message, and yet had a disease phenotype at diagnosis that was a morphologic facsimile of classic chronic phase CML. These patients presented with high white blood cell counts, neutrophilia, occasional basophilia, splenomegaly, and a hypercellular bone marrow with granulocytic hyperplasia and a left shift in myeloid maturation. Despite the striking resemblance between the early stages of bcr-negative and bcr-positive CML, disease progression manifests distinctly in these two disorders. In contrast to the blastic transformation that inevitably complicates bcr-positive CML, the natural history of our 11 Ph-negative, bcr-negative CML patients was characterized by increasing leukemia burden with leukocytosis, pronounced organomegaly, extramedullary infiltrates, and eventual bone marrow failure (anemia and thrombocytopenia) without marked increases in blast cells. Our current observations suggest that a chronic myeloid leukemia process can develop without associated changes in the bcr or c-abl genes. Although the initial phase of this disease is indistinguishable from CML, the presence or absence of molecular markers may aid in the prediction of the clinical course of Ph-negative CML.
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PMID:Philadelphia chromosome-negative chronic myelogenous leukemia without breakpoint cluster region rearrangement: a chronic myeloid leukemia with a distinct clinical course. 240 27

In the majority of Philadelphia (Ph)-positive chronic myeloid leukemia (CML) patients, the c-abl gene is fused to the bcr gene, resulting in the transcription of an 8.5 kb chimeric bcr-abl mRNA, which is translated into a p210bcr-abl fusion protein. In about 50% of the Ph-positive acute lymphoid leukemias (ALL), the bcr-abl gene fusion is identical to CML, while in 50% an alternative fusion between these two genes occurs, in which the central bcr-sequences are absent. This results in transcription of a 7 kb bcr-abl mRNA, encoding a P190bcr-abl fusion protein. Cloning and sequencing of the chimeric part of bcr-abl cDNAs from two Ph-positive CML patients in chronic phase showed that in one patient, as in the Ph-positive ALL, all central bcr sequences are absent, while in the other patient, part of the bcr central sequences are deleted. Therefore, we speculate that the presence of the 7 kb chimeric ALL type mRNA in one of the patients is not sufficient to drive an acute rather than a chronic leukemic process in this case. The deletions of the central bcr-sequences described here define the minimal sequence requirement of the bcr-abl fusion gene in CML patients so far.
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PMID:Chronic myeloid leukemia may be associated with several bcr-abl transcripts including the acute lymphoid leukemia-type 7 kb transcript. 220 36

Southern blot analysis detected a bcr gene rearrangement within leukemic cells of a Philadelphia chromosome-negative chronic myelocytic leukemia (CML) patient that led to transcription of a novel 7.3 kb bcr RNA species. Participation of the c-abl oncogene in this genomic recombination could be ruled out by in situ hybridization studies and Northern blot analysis.
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PMID:bcr Rearrangement without juxtaposition of c-abl in chronic myelocytic leukemia. 241 65


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