Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 93-kDa tyrosine protein kinase (p93) identified previously as the gene product of the c-fes proto-oncogene, is highly expressed in HL-60 leukemia cells induced to differentiate to the granulocyte or monocyte phenotype. We have now studied the relationship of p93 to the differentiation process by using a dimethyl sulfoxide (DMSO)-resistant subline of HL-60 cells (HL-60/DMSO) or the parental cell line treated with peptide or protein substrates of p93. Treatment of HL-60/DMSO cells with DMSO induced neither differentiation nor the expression of p93; however, cotreatment with IFN-alpha and DMSO resulted in partial differentiation and the concomitant induction of p93 activity. Treatment of wild-type HL-60 cells by the coaddition of the p93 substrates poly(Glu,Tyr)1:1, poly(Glu,Tyr)4:1, poly(Glu,Ala,Tyr)6:3:1, angiotensin II or vasoactive intestinal peptide with DMSO or IFN-tau partially blocked differentiation and concurrently diminished the induction of p93 activity. The inhibitory concentrations of the p93 substrates were related to their Km values. These results indicate that there is an obligatory association between the expression of p93 and granulocyte/monocyte differentiation in this cell line.
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PMID:Association of p93c-fes tyrosine protein kinase with granulocytic/monocytic differentiation and resistance to differentiating agents in HL-60 leukemia cells. 316 57

DNA of peripheral blood or bone marrow leukocytes from 8 normal subjects, 7 cases of acute lymphocytic leukemia (ALL), 2 of acute myelogenous leukemia (AML) and 1 of chronic myelogenous leukemia (CML), having been digested by endonuclease Eco RI or Pst I separately, was hybridized with the probes of 3' fragment (Pst I/Hind III) or 5' fragment (Hinc II/Pst I) of Abelson murine leukemia virus (A-MuLV) oncogene v-abl. The proto-oncogene c-abl, which is homologous to v-abl, was found amplified in 4 ALL, 1 CML and 1 AML. In one of these 4 ALL, c-abl was amplified even over 100 times. A new c-abl BamH I fragment with 6.7 kilobase pairs (kb) in length was observed in 2 ALL and 1 CML out of these 6 cases with amplification, but none of this fragment was found in the normal subjects or other leukemia patients. These 3 patients with the presence of 6.7 kb fragment were high risk ones and 2 of them had died, suggesting that 6.7 kb fragment be the index of poor prognosis. The amplification and rearrangement of c-abl imply the activation of proto-oncogene in leukemogenesis.
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PMID:[Amplification and rearrangement of proto-oncogene c-abl in human leukemia cells]. 321 75

Tumour necrosis factor (TNF) induces the lysis of many malignant cells in vitro and regression of some tumours in vivo. However, TNF is also a growth factor for normal fibroblasts, T cells and B cells and we have recently shown that TNF can also act as a growth factor for chronic B cell neoplasms, including hairy cell leukaemia and B-CLL. In these cells it promotes proto-oncogene expression, RNA and DNA synthesis and increases overall cell survival. Stimulation appears to be autocrine in nature since exposure of the neoplastic cells to recombinant TNF protein induces the corresponding messenger RNA and synthesis of the protein itself. TNF induced proto-oncogene expression and DNA synthesis occur over a substantially longer time period than when the cells are stimulated with agents such as TPA and Calcium ionophore (2), but we have no evidence that the delay represents the time taken to generate TNF dependent secondary cytokines such as IL-1 and IL6. Alpha interferon opposes TNF mediated activation and our recent data indicate that this effect is independent of alpha interferon down regulation of TNF receptors. It appears to be related instead to a decreased accumulation of TNF mRNA which occurs contemporaneously with an alpha interferon induced rise in 2-5 A synthetase. If TNF dependent growth is important for the survival of B-CLL cells, then agents which mimic alpha interferon or which block TNF induced autocrine growth would be predicted to be of therapeutic benefit.
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PMID:Effects of tumour necrosis factor and alpha interferon on chronic B cell malignancies. 326 1

Of 17 Moloney murine leukemia virus (MoMuLV)-induced rat thymomas, 2 contained rearrangements in c-myc. In one of these tumors the observed rearrangement was not due to the insertion of an intact MoMuLV provirus. The rearranged c-myc DNA fragment from this thymoma was cloned and examined by restriction endonuclease mapping, hybridization to MoMuLV proviral DNA probes, and DNA sequence analysis. These analyses revealed that the c-myc rearrangement in this tumor was due to the presence of a partially duplicated MoMuLV long terminal repeat (LTR) 5' to c-myc exon 1. The orientation of this LTR structure was opposite to the transcriptional orientation of c-myc. The sequences at the 3' flanking side of the LTR structure were derived from a cellular DNA region which maps to the same chromosome as c-myc (chromosome 7), although to a site distant from this proto-oncogene. These findings present evidence for a homologous recombination event occurring between sequences of two proviruses integrated on the same chromosome, one of which was inserted near the c-myc proto-oncogene. The recombination product contains three copies of the MoMuLV LTR 72-base-pair direct repeat and is associated with a high level of c-myc expression. The reciprocal product of this recombination was not detected. We propose that recombination between homologous sequences may play a significant role in the generation of chromosomal rearrangements and therefore in tumor induction and progression.
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PMID:Recombination between two integrated proviruses, one of which was inserted near c-myc in a retrovirus-induced rat thymoma: implications for tumor progression. 327 24

The ABL proto-oncogene on the Philadelphia chromosome is 'activated' by its translocation in a manner similar to its activation by the murine Abelson leukemia virus--with the formation of a fusion protein with a new N-terminus and enhanced tyrosine kinase activity. Study of this BCR-ABL fusion gene has led to the development of molecular probes which are beginning to play an important role in the diagnosis and clinical management of chronic myelogenous leukemia, and may ultimately lead to better understanding of the biology of the disease. The role of ABL on the Philadelphia chromosome in acute lymphoblastic leukemia is only now beginning to be understood, but is likely to be similar, and a new ABL species has already been identified by several groups. It is likely that this protein is the product of a fusion gene, as it is in chronic myelogenous leukemia, but definitive proof awaits molecular cloning of the translocation breakpoint. Aside from its activation by the Ph1 chromosome, ABL has not been found to have a role in any other human cancer.
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PMID:The ABL oncogene in human leukemias. 328 49

In chicken cells, we previously identified a set of proteins (p58-64) structurally related to, but distinct from, the products encoded by the c-ets proto-oncogene. We report here the isolation and nucleotide sequence of a cDNA encoding nuclear products of mol. wt 58, 60, 62 and 64 kd, indistinguishable from those detected in chicken cells. The p60 and p64 species appear to represent phosphorylated versions on serine and threonine residues of p58 and p62. The homology of p58-64 to other ets-related proteins, including the v-ets encoded domain of the transforming protein of avian leukemia virus E26 and p54c-ets, the translation product of the chicken (Ck) c-ets gene, is confined to two regions of 175 and 96 amino acid residues localized respectively at the carboxy-terminal domain and close to the amino-terminal domain of these molecules. This cDNA corresponds to a gene localized in a locus distinct from that of c-ets which is transcribed as a 4.0-kb RNA species in most chicken tissues. We also identified the human (Hu) c-ets-2-encoded products as two proteins of 60 and 62 kd, highly related to chicken p58-64. This, together with the fact that the amino acid sequence of the cDNA encoding p58-64 is 95% identical to the reported partial sequence of a Hu-c-ets-2 cDNA, indicates that p58-64 are the translation products of the Ck-c-ets-2 gene.
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PMID:Identification in chickens of an evolutionarily conserved cellular ets-2 gene (c-ets-2) encoding nuclear proteins related to the products of the c-ets proto-oncogene. 329 99

The relationship between the expression of the c-fos proto-oncogene and the expression of the class I major histocompatibility (MHC) antigens during the early stages of induced differentiation in three different leukemic cell lines was examined. In the U937 histiocytic lymphoma line TPA induced an increase in mRNA and cell surface MHC expression which followed induction of c-fos. In contrast, in the murine erythro-leukemia cell line, DMSO induced declining constitutive c-fos levels that were accompanied by declining mRNA and cell surface MHC expression. In the pluripotent HL60 promyelocytic line induction of macrophage differentiation with TPA led to c-fos induction and rising MHC levels, whereas induction of granulocyte differentiation with DMSO did not induce c-fos expression and was followed by declining MHC levels. Taken together, the results suggest that the c-fos proto-oncogene might be involved in the control of class I MHC antigen expression during differentiation.
Leukemia 1987 Mar
PMID:Expression of major histocompatibility class I genes in differentiating leukemic cells is temporally related to activation of c-fos proto-oncogene. 331 38

The myelodysplastic syndrome (MDS) or preleukaemia is a haematological disorder characterized by low blood counts, bone marrow cells of abnormal appearance and progression to acute leukaemia in as many as 30% of patients. The distinctive preleukaemic and leukaemic phases of this disease make it an attractive model for neoplastic progression in human tumours. We reasoned that, because dominantly transforming genes (such as mutant alleles of ras proto-oncogenes) are found so frequently in acute leukaemia, the search for these genetic lesions during the clinical course of patients with MDS might give us insight into the function of oncogenes in leukaemogenesis. We report here that bone marrow cells from two of four patients with preleukaemia, and from one patient who progressed to acute leukaemia from MDS, contained a transforming allele of the Ki-ras proto-oncogene. In one preleukaemic patient, a novel mutation in codon 13 of this ras gene was detected in bone marrow cells harvested 1.5 years before the acute leukaemia developed. Our findings provide evidence that ras mutations may be involved in the early stages of human leukaemia.
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PMID:Mutations of the Kirsten-ras proto-oncogene in human preleukaemia. 331 61

The int-1 proto-oncogene is the first cellular gene discovered and implicated in tumorigenesis solely on the basis of repeated insertional mutations that activate transcription of the gene. The gene is silent in most tissues but expressed in the embryonic central nervous system, in the late (post-meiotic) stages of spermatogenesis, and in a high proportion of mouse mammary tumor virus-induced carcinomas, when a provirus is inserted upstream or downstream of the coding domain. The functional significance of int-1 in the oncogenic process is supported by the demonstration that murine leukemia virus-based vectors carrying the gene can alter the morphology and growth properties of an established line of mammary epithelial cells. The predicted primary protein product of the int-1 gene is 370 amino acids in length and cysteine-rich; immunoprecipitation with anti-peptide antibodies reveals multiple species of int-1 protein, due to asparagine-linked glycosylations and probable cleavage of a signal peptide. However, the active product of the gene and its biochemical behavior during normal development and mammary tumorigenesis are not known.
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PMID:The int-1 proto-oncogene. 333 19

This paper analyzes the hematologic features and outcome of 13 patients with chromosome 5 abnormalities (monosomy 5 or deletion of 5q), either isolated or with additional anomalies. Among four patients with isolated del (5q), two had a stable refractory macrocytic anemia with thrombocytosis (5q-syndrome). All nine patients with complex karyotypes had acute leukemia or refractory anemia with excess of blasts in acute transformation; two cases were TdT-positive, with a lymphoid or a mixed phenotype. In seven patients, preleukemia preceded overt leukemia, and in six, a prior therapeutic, or occupational exposure to mutagens/carcinogens had occurred. Additional chromosome 7 abnormalities were seen in four cases. The median survival of patients with complex karyotypes was 19 months from the time of diagnosis of the hematologic disorder and 5 months from the time of identification of the chromosome 5 abnormality. Pathogenetic implications of the chromosome 5 monosomy or del (5q) through a proto-oncogene activation and the putative hemopoietic stem cell involvement in a clonal disease are discussed.
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PMID:Hematologic and clinical features of patients with chromosome 5 monosomy or deletion (5q). 335 40


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