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)

The p53 gene encodes a nuclear phosphoprotein and is now considered as a tumor suppressor gene. Mutations of the p53 gene have frequently been observed in several types of solid tumors and are believed to be implicated in the development of these tumors. Recent studies have shown that the p53 gene is altered in chronic myelogenous leukemia (CML) in blast crisis. In CML, alterations of the p53 gene may play an important role in the development of blast crisis. More recently, p53 mutations have been reported in other types of hematologic neoplasms, such as acute leukemia, adult T-cell leukemia, and malignant lymphoma. These observations suggest that inactivation of the p53 gene is involved in the tumorigenesis of various types of hematologic neoplasms.
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PMID:[Mutations of the p53 gene in hematologic neoplasms]. 151 57

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

Twenty-nine patients with acute myelocytic leukemia (AML) and 14 patients with Philadelphia chromosome-positive chronic myelocytic leukemia (CML) were analyzed to detect the presence of mutations in their ras genes by the polymerase chain reaction and oligonucleotide hybridization methods. Deoxyribonucleic acid (DNA) isolated from blood or bone marrow samples was screened for mutations in codons 12, 13 and 61 of N-ras and in codons 12 and 61 of K-ras and H-ras. We detected mutations of the ras gene in 7 patients with AML (7/29), all in N-ras. The mutations were 3 GGT- greater than GAT transitions in codon 12, 1 GGT- greater than TGT transition in codon 13, and 3 CAA- greater than AAA transitions in codon 61. No correlation has been observed between French-American-British subtypes and the incidence of N-ras mutation, nor between cytogenetic changes and the incidence of N-ras mutation. All ras gene mutations detected by the oligonucleotide hybridization method were further confirmed by direct sequencing. No mutations were detected in ras genes in samples from the 14 Philadelphia chromosome-positive CML patients (12 in chronic phase, 2 in blastic phase). These findings are in line with previous results indicating that ras gene mutations in the codons tested play only a small role in the tumorigenesis of CML.
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PMID:Mutation analysis of the ras gene in myelocytic leukemia by polymerase chain reaction and oligonucleotide probes. 168 80

The Ph chromosome was the first specific karyotype abnormality associated with a particular neoplastic disease in humans. For many years it was suspected that chromosome abnormalities might cause cancer by alteration of specific genes or their expression. Significant recent developments in our understanding of the molecular consequences of the Ph translocation strengthen that assumption. The Ph translocation generates a hybrid gene consisting of 5' regulatory, promotor, and exon sequences of the bcr gene on chromosome 22 fused to 3' exons and polyadenylation/termination sequences of the ABL proto-oncogene from chromosome 9. It is well established that fusion of bcr and abl genes plays a crucial role in the pathogenesis of CML and ALL. Molecular methods can therefore be used as diagnostic tools to detect the Ph chromosome. Presently, the model of oncogenesis provided by our knowledge of how the abl proto-oncogene becomes activated as a result of the Ph translocation is one of the clearest models of oncogene activation. Despite the progress made, many areas remain to be explored. One important question is, how the hybrid protein is involved in leukemia. Research aimed at investigating the normal function of abl and bcr may be important in efforts to understand their abnormal functioning in leukemia and to increase our understanding of the disease.
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PMID:Molecular insights into the Philadelphia translocation. 205 Jun

Retroviruses first attracted attention as the etiological agents of tumors in various animals, including birds, rodents and primates. The retrovirus-induced tumors comprise above all T- and B-cell leukemias/lymphomas, chronic myelogenous leukemia and mammary carcinomas, and are characterized by a long latent period between infection and manifestation of the disease. Since their detection, oncogenic retroviruses have been the object of intense study contributing to our knowledge of basic mechanisms and molecular events involved in carcinogenesis in general. An essential step in the retrovirus life cycle is the covalent integration of the double-stranded DNA copy of viral RNA into the cellular genome, forming the provirus. The proviruses are quite stable and are generally a permanent acquisition for the cellular genome. Therefore, the presence of the provirus can have profound genetic implications for the host cell. There are at least three main routes that are assumed to lead to retroviral oncogenesis: Transduction of cell-derived oncogenes (v-onc) carried by some retroviruses, activation of cellular proto-oncogenes (c-onc) in cis by insertional mutation or activation of cellular genes in trans by virus encoded transcription factors.
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PMID:The significance of retroviruses in oncology. 209 76

The last decade has been very exciting for cancer cytogeneticists. At the start of the decade, the role of cytogenetics in clinical medicine was still unclear. Many felt that such investigations were largely of academic interest. Today, cytogenetic investigations are considered essential in many cancers, where they contribute in diagnosis, staging, choice of therapeutic protocol, and monitoring of the effects of therapy. The number of primary chromosome changes in human cancer exceeds 100, and while the majority of these changes are associated with haematological malignancies, the contribution from the solid tumours is now growing rapidly. Closer ties between scientists and physicians involved in laboratory and clinical medicine have resulted in the emergence of many well-defined cytogenetic-clinicopathological entities. With the advances in molecular biology that characterized the 1980s came the disappearance of all scepticism about the critical role played by chromosome change in oncogenesis. To date, we have learned more about the details of cancer biology in chronic myeloid leukaemia and the lymphoid malignancies through the molecular dissection of primary chromosome changes than through any other approach. Further studies will, no doubt, lead us to an understanding of the molecular basis of many of the primary and secondary chromosome changes that are non-randomly acquired in human cancer.
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PMID:Chromosome abnormalities in chronic myeloid leukaemia. A model for acquired chromosome changes in haematological malignancy. 224 54

A number of protooncogenes have been implicated in human tumorigenesis. The ABL oncogene is consistently rearranged and activated as a consequence of the translocation t(9;22) that gives rise to the Philadelphia chromosome in chronic myeloid leukemia and in some cases of acute lymphoblastic leukemia. Here we describe rearrangement of ABL in a different type of malignancy. The glioblastoma cell line A172 lacks germline alleles of ABL. A recombination event, presumably followed by a duplication, has created two ABL alleles in which exon 11 is joined to chromosome 16 sequences. Although the main body of ABL exons was still present, two considerably shortened ABL mRNAs of 3.8 and 2.8 kilobases were detected; the 3.8-kilobase mRNA hybridized exclusively to an exon IB probe. Neither mRNA hybridized to an ABL probe encompassing part of the tyrosine kinase domain. Thus, the cell line A172 is able to survive in the absence of a functional ABL gene product, indicating that the role of ABL is unlikely to be "housekeeping."
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PMID:Rearrangement of the human ABL oncogene in a glioblastoma. 233 39

Chromosomal translocation is one mechanism by which cellular oncogenes may be activated during tumorigenesis. The translocation of the abl oncogene to the Philadelphia chromosome in chronic myelogenous leukemia (CML) results in a new RNA transcript that fuses sequence from chromosome 22 to sequence from the abl oncogene. This RNA presumably codes for a new abl-related protein product found in CML, the activity of which is different from the normal abl protein. The molecular structure of the translocation varies from patient to patient, and the individual variation in RNA transcript and protein product remains to be defined. This report describes the frequent occurrence of chromosomal deletion within the 9q+ chromosome during these translocations. The location of the deletions suggests that some mechanism maintains the chromosomal breakpoint on the Philadelphia chromosome within a limited region. These deletions complicate the interpretation of Southern blots as a means of detecting the translocation.
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PMID:Frequent and extensive deletion during the 9,22 translocation in CML. 302 Dec 64

Chronic myelogenous leukemia (CML) is a hematopoietic malignancy characterized by an indolent chronic phase that invariably leads to a "blast crisis" indistinguishable from acute leukemia. Using a sensitive assay based on gene transfer and tumorigenesis, we sought evidence that damage to protooncogenes might figure in the progression from the chronic to the blast phase of CML. Seven of the 12 patients with CML examined in this manner harbored transforming genes. Mutations in RAS protooncogenes were detected in the leukemic cells from 1 of 6 chronic-phase patients, and 3 of 6 blast-crisis patients. In addition, a presently unidentified transforming gene (neither RAS nor RAF) was detected in 1 patient with chronic phase and 1 with blast crisis. Our data indicate that mutations in RAS genes may play diverse roles in the pathogenesis of CML.
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PMID:Transforming genes in chronic myelogenous leukemia. 327 21

It is clear that there are at least two classes of cancer-related genes. The more characterized of these are the oncogenes, whose activation appears to play a major role in human neoplasia. There are now two families of oncogenes, the myc and ras families, whose cooperation seems capable of transforming normal cells in culture to tumorigenic cells. As such, they appear to form complementation groups with immortalizing and transforming properties, respectively. Moreover, the oncogenes can be subclassified as tyrosine kinases or kinase related, GTP binding proteins, growth factors or growth factor receptors or nuclear proteins. More than 20 viral oncogenes have been identified, for which more than 30 proto-oncogenes or pseudogenes exist in the human genome. Many of these have been cloned, characterized to some extent, and mapped to particular chromosomes or regions of chromosomes. Further, more than 20 additional putative oncogenes or transforming genes have been identified by tumor DNA transfection studies or at sites of integration or translocation for which no viral transforming gene cognates exist. Oncogenes can be activated by increased or unregulated expression, increased copy number (duplication, amplification), or somatic mutation resulting in a protein with increased oncogenic potential. Examples of all of these mechanisms can be found in several specific human cancers or leukemias. The cytogenetic correlate of enhanced expression is a translocation between two chromosomes at specific breakpoints with no net loss of genetic material (e.g., increased c-myc expression resulting from the 8;14 translocation in Burkitt's lymphoma). The phenomenon of increased gene copy number can sometimes be visualized as trisomy or tetrasomy for a particular chromosome but more dramatically as the development of extrachromosomal DMs or as chromosomally integrated HSRs (e.g., the N-myc gene amplification seen in neuroblastoma). Finally, certain somatic mutations can be associated with translocations (e.g., the bcr/abl fusion product created as a result of the 9;22 translocation in chronic myelogenous leukemia), but they are more commonly submicroscopic (as characterized by point mutations in the ras gene family). Evidence is accumulating for a second class of cancer-related genes whose absence or inactivation is associated with tumorigenesis. These genes are associated at the cytogenetic level with chromosomal deletions, in which the breakpoints may be variable, but specific, common regions are consistently deleted.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The involvement of oncogenes and suppressor genes in human neoplasia. 331 93


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