Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have carried out the molecular and cell-biological analysis on Ph1-positive leukemias in this study. Five out of nine Ph1-positive ALL cases showed molecular rearrangement within the classical bcr sequence (or M-bcr), similar as those in 47 CML cases. We examined 4 cases of Ph1-positive ALL presenting no rearrangement of M-bcr and found that, in 2 of 4 cases, one showed the breakpoint in a 5 kb segment of the bcr gene first intron (bcr-2) and the other in bcr-1, 16 kb upstream of bcr-2. Ph1-positive ALL frequently showed biphenotypical or biclonal phenotypes of myeloid and lymphoid lineages. Furthermore, we demonstrated the ability of two Ph1-positive ALL cell lines to differentiate into monocytic lineage in vitro, thus suggesting the possibility that these Ph1-positive ALL cells might reside on the stage of multipotent stem cell along the hematopoietic cell differentiation. Two out of 31 CML cases showed the mutations of the ras genes by the polymerase chain reaction; one case in the crisis phase and the other in the chronic phase. However, no mutations of the fms genes was detected. Two cases in the crisis phase of 24 CML patients (11 cases in the chronic phase and 13 cases in the crisis phase) contained rearrangements of the p53 gene by Southern analysis. Furthermore, the transcriptional alteration was found in 2 CML-BC and 2 CML-BC derived cell lines' samples, suggesting a important role of the p53 gene in the transformation of CML into the crisis phase.
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PMID:[Rearrangement and expression of bcr-abl genes in CML and ALL]. 189 Jul 38

We tested a population of over 60 patients with chronic myelogenous leukemia (CML) for changes in the structure and expression of the p53 gene, which is located on chromosome 17. Six of 27 (22%) blast crisis samples and 3 of 5 (60%) accelerated phase samples had rearrangements of chromosome 17, whereas only 3 of 42 (7%) chronic phase patients had cytogenetic changes in chromosome 17. There was no loss of heterozygosity during the transition to blastic crisis among seven individuals who were informative for polymorphic probes for regions in or around the p53 gene on 17p. One patient in the chronic phase and one patient in the blastic phase of the 61 CML patients studied exhibited rearrangements of the p53 gene that were detectable by Southern analysis. One p53 allele was rearranged in the chronic phase patient and both p53 alleles were rearranged in the blastic phase patient. The p53 messenger RNA (mRNA) was of normal size (2.8 kb) in chronic phase and blast crisis, and the expression of the p53 gene was at least as high or higher in blast crisis as in the chronic phase of CML. The high incidence of abnormalities of chromosome 17 in blast-crisis CML found in our studies and the discovery of rearrangements of the p53 gene in two CML patients studied suggest that further study with probes for the p53 gene and anonymous polymorphic sites in chromosome 17 should be conducted in CML.
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PMID:Rearrangement and expression of p53 in the chronic phase and blast crisis of chronic myelogenous leukemia. 196 14

A patient with typical Philadelphia chromosome (Ph1)-positive chronic myelocytic leukemia (CML) was studied during sequential phases of disease: (1) initial chronic phase; (2) myeloid blast crisis; (3) second chronic phase; and (4) accelerated disease. A point mutation in the coding sequence of the p53 gene first appeared concomitantly with the blast crisis and then disappeared with the re-establishment of a second chronic phase. The chromosomal concomitant of the molecular alteration was a deletion of 17p. These observations suggest that abnormalities of the p53 anti-oncogene are temporally related to the clinical progression of some cases of CML and are probably responsible for the development of blast crisis in these cases.
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PMID:Correlation between molecular and clinical events in the evolution of chronic myelocytic leukemia to blast crisis. 203 25

DNA from 135 patients with chronic myelogenous leukemia (CML) at various clinical stages and Philadelphia (Ph1) chromosome positive acute lymphoblastic leukemia was investigated for alterations in a variety of proto-oncogenes which have been implicated in the evolution of CML from its chronic phase to blast crisis. The most common genetic change found in the evolution of typical Ph1 chromosome positive CML to blast crisis was an alteration of the p53 gene involving either a rearrangement, a deletion, or a point mutation in the coding sequence of the gene. Alterations of the p53 gene were found in the myeloid and the rare megakaryocytic variant of blast crisis but were absent in the lymphoid leukemic transformants. Gross structural alterations were seen in 11 of 54 (20%) of myeloid or unknown phenotypes of blast crisis and in only 1 of 44 chronic phase cases. Eight examples of mutations in the open reading frame of the p53 gene at codons 49, 53, 60, 140, 202, 204, 238, and 239 were observed in blast crisis patients. Mutations in the N-RAS gene were rare in typical blast crisis (2 of 27 cases) but were found in megakaryocytic and Ph1 negative myeloid blast crisis. We concluded that heterogeneous alterations in the p53 gene and occasionally in the N-RAS genes accompany the evolution of chronic phase CML to blast crisis.
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PMID:The spectrum of molecular alterations in the evolution of chronic myelocytic leukemia. 204 Jun 94

Chronic myelogenous leukemia (CML) is characterized cytogenetically by the presence of the Philadelphia chromosome, which is the result of a reciprocal translocation between chromosomes 9 and 22. Analysis of the rearranged chromosome 22 have demonstrated that the DNA breakpoints fall within a 5.8-kilobase (kb) region termed M-bcr. In Ph1-acute lymphocytic leukemia, approximately half of the patients have a breakpoint within M-bcr, whereas the remaining half have the break within the first intron of the BCR gene (m-bcr). We have investigated five cases with CML in the blastic phase to search the molecular mechanism of blastic crisis in CML. Using a method of reverse transcriptase-polymerase chain reaction (RT-PCR), we have identified both types of breakpoints in samples of the three cases, suggesting the existence of M-bcr/ABL and m-bcr/ABL chimeric mRNAs in the RNA samples derived from blasts of the three cases. We have further analysed for alterations in the p53 gene in those cases. The p53 gene is now considered to be a tumor suppressor gene and its mutations play a role in the development of many human malignancies. We have attempted to determine whether the p53 gene is involved in the mechanism of blastic crisis in CML. Using the methods of RT-PCR and single stand-conformational polymorphism (SSCP), we have detected expression of only a mutated p53 allele in a case with CML blastic crisis, indicating that inactivation of the p53 gene in both alleles may contribute to the blastic crisis in this case. Accumulation of molecular analysis in more cases will clarify the mechanism of blastic crisis in CML.
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PMID:[Analysis of Ph1-positive leukemia by PCR]. 206 73

All patients with chronic myelogenous leukemia (CML) undergo clinical transition from chronic to acute phase. This transition is often associated with deletion of the short arm of chromosome 17 in the form of the i(17q) aberration. Since the p53 gene is a suppressor gene and is located on 17p13, we examined the possibility that it is inactivated during progression of CML. Therefore, we studied the structure and expression of p53 in the leukemic cells of a large number of CML patients in acute phase. We found that although the gene is rarely rearranged, one p53 allele is completely deleted in patients with the i(17q) aberration as well as in some patients who do not show karyotypic changes. In all of these patients the remaining allele is inactivated through loss of expression, rearrangement, or point mutation. Detailed analysis of some patients who carry both p53 alleles indicated neither loss of expression nor structural alterations. It appears that p53 loss of function is associated with progression of around 25% of CML patients.
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PMID:p53 in chronic myelogenous leukemia in acute phase. 206 8

The expression of the myeloperoxidase (MPO) gene was studied, by means of Northern blot analysis in 14 cases of acute myeloid leukemia (AML), 11 cases of chronic myeloid leukemia (CML), and 6 cases of CML blast crisis, and in HL60 cells before and after induction of terminal differentiation with retinoic acid (RA), phorbol esters (TPA), or vitamin D. The expression of a panel of cell cycle-related genes, namely C-MYC, histone H3, ornithine decarboxylase, P53, vimentin, and calcyclin, was also studied in the same cell populations. Our results indicate that: (a) MPO gene expression (steady state mRNA levels) is strictly confined to the first stages of myeloid differentiation, reaching its peak at the promyelocyte stage and becoming undetectable in mature granulocytes and monocytes; (b) cells devoid of any detectable MPO enzymatic activity such as leukemic basophils have a high content of MPO mRNA; and (c) MPO gene expression is not related to the growth activity of the cell population. Finally, our results show that the pattern of expression of growth-regulated genes in the neoplastic myeloid disorders AML, CML, and CML blast crisis is remarkably different.
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PMID:Expression of the myeloperoxidase gene in acute and chronic myeloid leukemias: relationship to the expression of cell cycle-related genes. 254

Molecular structural analysis of the p53 gene in patients with Philadelphia chromosome-positive chronic myelogenous leukemia (CML) indicates a significant incidence of gene rearrangements in patients at either accelerated phase or blastic crisis. Southern blot analysis of genomic DNA hybridizing with either genomic or cDNA p53 specific probes indicated that 30% of the CML patients at blastic crisis phase exhibited rearrangements, mostly mapping downstream to the first non-coding exon. This is compatible with the observation that the progression of CML from the chronic to the acute phase involves frequent aberrations in chromosome 17, to which the p53 oncogene has been mapped. Therefore, we suggest that one of the pathways of development of CML to the acute phase is associated with aberrations in the p53 nuclear oncogene.
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PMID:Rearrangements in the p53 gene in Philadelphia chromosome positive chronic myelogenous leukemia. 231 66

The bcr gene plays a critical role in the pathogenesis of two human leukemias associated with the Philadelphia chromosome: chronic myelogenous leukemia (CML) and acute lymphoblastic leukemia (ALL). In both instances a chimeric gene, formed between bcr and the abl protooncogene, results in expression of fused bcr-abl proteins with tyrosine kinase activity. There is controversy regarding the normal gene products of bcr. We investigated this problem by several techniques and found proteins of 190/185, 155, 135, 125, 108, 83 and 47 kDa in several human cell lines by immunoprecipitation with two distinct site-directed anti-bcr antibodies termed anti-bcr(738-753) and anti-bcr(898-911). The 190/185, 155, 125 and 108 kDa proteins were consistently detected by anti-bcr(898-911) antibodies by immunoblotting. Antibodies pre-reacted with excess bcr peptide did not detect these proteins. These proteins were labeled with [32P]orthophosphate in vivo and in vitro by [gamma 32P]ATP in immune complex kinase assays performed with anti-bcr antibodies indicating that these proteins are phosphorproteins. Following labeling in kinase assays, phosphoamino acid analyses detected both phosphoserine and phosphothreonine. In structural studies using one dimensional peptide maps derived by partial V8 protease treatment, the 185, 155, 135, 125 and 108 kDa proteins shared several peptide fragments but contained unique fragments as well. Similarly 2-dimensional maps of proteins labeled in the kinase assay exhaustively digested with trypsin, revealed homology between the 155, 135, 125, 108, and 83 kDa proteins. bcr proteins sedimented in glycerol gradients as putative complexes detected in the cytoplasm of the cell. A 47 kDa protein as well as the recently identified Ph-P53 protein appeared to be associated with bcr proteins based on their co-sedimentation in glycerol gradients and co-immunoprecipitation with several different anti-bcr antibodies. None of the proteins exhibited a precursor-product relationship in pulse-chase experiments conducted with [35S]methionine. We conclude that human cells express several different bcr gene products ranging in size from 190 to 83 kDa, and that these proteins can form specific intracellular cytoplasmic complexes with other cellular proteins.
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PMID:Characterization of bcr gene products in hematopoietic cells. 264 52

Molecular mechanisms responsible for the clinical progression of chronic myelocytic leukemia to its accelerated phase or to blast crisis have not been defined. We found alterations of the p53 gene (p53 is a 53-kDa nuclear protein) including deletions and rearrangements in 8 of 34 patients in blast crisis and 1 of 4 patients in the accelerated phase, but in only 1 of 38 patients in the chronic phase of chronic myelocytic leukemia. Only two other examples of p53 gene alterations were found among 203 patients with hematologic malignancies and solid tumors. Transcripts of the p53 gene were uniformly found in chronic-phase cells, but gene expression was variable in blast crisis, and transcripts were reduced or undetectable in 10 of 16 patients. Heterogeneous alterations in the structure and expression of the p53 gene appear to be relatively frequent in blast crisis and may be involved in the evolution of disease.
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PMID:Alterations in the p53 gene and the clonal evolution of the blast crisis of chronic myelocytic leukemia. 277 57


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