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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A rearrangement of the c-H-ras locus was detected in a T-cell line (DA-2) established from a Moloney leukemia virus-induced tumor. This rearrangement was associated with the high-level expression of H-ras RNA and the H-ras gene product, p21. DNA from DA-2 cells transformed fibroblasts in DNA transfection experiments, and the transformed fibroblasts contained the rearranged H-ras locus. The rearrangement involved one allele and was present in tissue from the primary tumor from which the cell line was isolated. Cloning and sequencing of the rearranged allele and comparison with the normal allele demonstrated that the rearrangement was complex and probably resulted from the integration of a retrovirus in the H-ras locus between a 5' noncoding exon and the first coding exon and a subsequent homologous recombination between this provirus and another newly acquired provirus also located on chromosome 7. These events resulted in the translocation of the coding exons of the H-ras locus away from the 5' noncoding exon region to a new genomic site on chromosome 7. Sequencing of the coding regions of the gene failed to detect mutations in the 12th, 13th, 59th, or 61st codons. The possible reasons for the complexity of the rearrangement and the significance of the activation of the H-ras locus to T-cell transformation are discussed.
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PMID:Activation of the c-H-ras proto-oncogene by retrovirus insertion and chromosomal rearrangement in a Moloney leukemia virus-induced T-cell leukemia. 254 6

The N-ras gene is the only member of the ras family which has never been naturally transduced into a retrovirus. In order to study the in vitro and in vivo oncogenicity of N-ras and to compare its pathogenicity to that of H-ras, we have inserted an activated or a normal form of human N-ras cDNA into a slightly modified Harvey murine sarcoma virus-derived vector in which the H-ras p21 coding region had been deleted. The resulting constructions were transfected into NIH 3T3 cells. The activated N-ras-containing construct (HSN) induced 10(4) foci per microgram of DNA and was found to be as transforming as H-ras was. After infection of the transfected cells by either the ecotropic Moloney murine leukemia virus or the amphotropic 4070A helper viruses, rescued transforming viruses were injected into newborn mice. Both pseudotypes of HSN virus containing activated N-ras induced the typical Harvey disease with similar latency. However, we found that the virus which contained normal N-ras p21 (HSn) was also pathogenic and induced splenomegaly, lymphadenopathies, and sarcoma in mice after a latency of 3 to 7 weeks. In addition, Moloney murine leukemia virus pseudotypes of N-ras caused neurological disorders in 30% of the infected animals. These results differed markedly from those of previous experiments in which we had inserted the activated form of N-ras in the pSV(X) vector: the resulting SVN-ras virus was transforming on NIH 3T3 cells but was poorly oncogenic in vivo (M. Souyri, C. F. Koehne, P. V. O'Donnel, T. H. Aldrich, M. E. Furth, and E. Fleissner, Virology 158:69-78). However, similarly poor oncogenicity was also observed when the v-H-ras coding sequence was inserted in pSV(X) vector, which indicated that the vector sequences play a crucial role in the pathogenicity of a given oncogene. Altogether, these data demonstrated unequivocally that N-ras is potentially as oncogenic as H-ras and that such oncogenic effect could depend on the vector environment.
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PMID:Oncogenicity of human N-ras oncogene and proto-oncogene introduced into retroviral vectors. 254 8

Human continuous bone marrow cultures were established from intraoperative marrow specimens and infected with amphotropic murine leukemia virus (Am-MuLV) pseudotypes of Kirsten or Harvey murine sarcoma virus, and the biologic effects were compared with mouse continuous bone marrow cultures. Cultures were tested for production of total nonadherent granulocytes and granulocyte-macrophage progenitor cells (GM-CFUc); virus replication by supernatant reverse transcriptase activity; percentage of adherent and nonadherent cells and GM-CFUc that released virus by infectious center assay; and for synthesis of Harvey ras p21 protein. High-efficiency, stable Am-MuLV infection of over 90% of human marrow-culture nonadherent and adherent cells and both seven- and 14-day GM-CFUc were detected as Kirsten or Harvey pseudotype virus release by infectious center assay. Synthesis of Harvey ras p21 was detected in the adherent and nonadherent cell populations of human as well as mouse continuous marrow cultures infected with Kirsten or Harvey pseudotype virus. In contrast to data with mouse cultures, cumulative production of GM-CFUc and differentiated granulocytes in human cultures was not detectably altered by Harvey or Kirsten virus infection, and all cultures ceased to produce hematopoietic cells by 20 weeks. Of 54 virus-infected cultures in ten separate experiments, 13 produced a second peak of nonadherent cells (greater than 10(5) per flask) after 20 weeks, significantly more frequently than did control uninfected cultures (one of 32). When subcultured, these harvests produced permanent Epstein-Barr virus (EBV)-transformed pre-B cell lines that released the original inoculating pseudotype virus. Thus, Am-MuLV is a potentially valuable vector for inserting genetic sequences by recombinant techniques into human hematopoietic and stromal cells in culture; however, activation of EBV may be a significant complication.
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PMID:Amphotropic retrovirus vector transfer of the v-ras oncogene to human hematopoietic and stromal cells in continuous bone marrow cultures. 257 39

Leukemic cell growth in the marrow microenvironment may be modulated by stromal cell products, including stimulatory growth factors and the inhibitory regulator prostaglandin E. The production of both of these stromal cell products induced by cytokine mediators appears to be closely linked. Cyclic AMP (cAMP) is an intracellular second messenger that inhibits myeloid cell proliferation and is produced in myeloid leukemia cells on stimulation of adenylate cyclase enzyme by prostaglandin E1 (PGE1). Cells expressing the product of an RAS oncogene have been observed to display diminished hormone-stimulated adenylate cyclase of membranes. If this observation were applicable to myeloid cells, a potentially important mode for leukemia cells expressing p21 RAS to escape inhibitory regulation within the hematopoietic microenvironment would be identified. We studied an interleukin-3 (IL-3)-dependent myeloid cell line, NFS/N1.H7, and a derivative line transfected with H-RAS codon 12 (T24) oncogene, H7 Neo Ras.F3, for inhibition of proliferation by PGE1, 1 microM, alone or in combination with pertussis toxin, which inactivates Gi, an inhibitory regulatory guanosine triphosphate (GTP)-binding protein of adenylate cyclase. NFS/N1.H7 cells were inhibited in interleukin-3-dependent proliferation (dose range, IL-3 10 to 100 U/mL) by PGE1 79 +/- 11%, by pertussis toxin 51 +/- 9%, and by the combination 92 +/- 2%, whereas H7 Neo RAS.F3 was inhibited 51 +/- 7%, 6 +/- 2%, or 58 +/- 9% by PGE1, pertussis toxin, and the combination, respectively. These differences in capacity for inhibition by adenylate cyclase agonists between RAS-transfectant cells (lower inhibition) versus parent cells (greater inhibition) were all highly significant (P less than .0005). Intracellular cAMP formed on PGE1 stimulation of pertussis-intoxicated cells was 150% lower in RAS-transfectant cells than in parent cells. The adenylate cyclase activity of membranes from pertussis-intoxicated RAS-transfected cells was 1.5 to two times lower than that of pertussis-intoxicated parent-cell membranes on Mg2+-dependent activation by hormone and/or guanine nucleotide. However, very similar adenylate cyclase activity was observed in oncogenic p21 RAS-containing membranes compared with parental membranes under conditions of direct activation by 4 mM Mn2+ and forskolin, where inhibitory or stimulatory G-protein influences are minimal. These studies showed diminished adenylate cyclase activity in mutant RAS-bearing myeloid-cell membranes compared with parent-cell membranes independent of the pertussis toxin-sensitive G protein, Gi.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effector function for RAS oncogene in interleukin-3-dependent myeloid cells involves diminished efficacy of prostaglandin E1-mediated inhibition of proliferation. 267 12

A high incidence of multiple primary neoplasms has been observed in our patients with ATL in comparison to persons with other forms of hematologic malignancy who we have observed during the past 24 years (1963-1985). Five of 15 patients with ATL (33.3%) have had at least one other associated neoplasm in comparison to only 44 of 1156 patients with other forms of hematological malignancy (3.8%). The incidence figures for secondary neoplasms associated with the other hematologic malignancies were 4.3% (16/370) for acute non-lymphocytic leukemia (ANLL), 2.2% (2/90) for acute lymphocytic leukemia (ALL), 4.8% (1/21) for acute unclassifiable leukemia, 2.2% (5/225) for chronic myelogenous leukemia, 4.7% (2/43) for chronic lymphocytic leukemia, 5.9% (8/136) for malignant monoclonal gammopathy and 3.7% (10/271) for malignant lymphoma. The incidence of multiple neoplasms in patients with ATL in comparison to those with other hematological malignancies was significant (p less than 0.01 or p less than 0.001). The neoplasms associated with ATL have been adenocarcinoma of the thyroid or lung, and squamous cell carcinoma of the larynx, lip or lung. We identified ATL-derived factor (ADF) in the cytoplasm of the secondary neoplasms of the ATL patients by means of indirect immunofluoroscopy and immunohistochemical techniques utilizing anti-ADF antibody. We also identified ras p21 products in these neoplasms by means of p21 ras monoclonal antibody studies. The possibility that HTLV-I was the cause of the secondary neoplasms thus was investigated.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Studies on association between the ATL and the development of multiple malignant neoplasms--analysis of 1171 cases of hematological malignancies during the past 24 years]. 268 7

A boy with acute lymphoblastic leukemia (ALL) who underwent lineage switch at relapse is reported. The second leukemia was myeloid in nature (acute myeloid leukemia, AML), characterized by predominantly My 9 positive blasts at first and at second relapse. Cytogenetic studies at second relapse revealed the translocation (9;11) (p21;q23) in all examined blasts. This is typical for myelomonocytic leukemia. The nature of the relapse and the occurrence of t(9;11) translocations in acute leukemia are discussed.
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PMID:Lineage switch and translocation t(9;11) in acute leukemia. 271 37

We have studied the immunophenotypic and genotypic characteristic of acute nonlymphoblastic leukemias (ANLL) in infants aged less than one year. Sixty-four percent of cases (16/25) showed a myeloid or myelomonocytic differentiation pattern and 10 of these were classified as FAB M5 (7 M5a, 3 M5b). Only seven of the latter cases expressed the CD14 antigen. Acute megakaryocytic leukemia with a high number of glycoprotein IIb/IIIa or IIIa positive blasts were identified in five patients. Erythroleukemia with a high percentage of rather mature glycophorin A positive erythroblasts were diagnosed in two infants. Cytogenetic studies were successfully performed in all 20 cases investigated. Abnormalities involving chromosome 11 were present in 10 of 17 patients with an abnormal karyotype including five cases with a t(9;11)(p21;q23). Immunoglobulin (Ig) and T cell receptor (TCR) gene analyses were performed in 20 patients. A rearrangement of Ig heavy chain sequences was detected in five cases (20%), one of whom exhibited multiple rearranged fragments. Three of these patients showed additional TCR delta-chain gene rearrangements, while Ig kappa, TCR beta- as well as TCR gamma-chain genes showed a germline configuration in all cases analyzed. Our study confirms the high incidence of myelomonocytic and monoblastic subtypes in infants with ANLL, which are particularly closely associated with chromosome 11 abnormalities. However, we also observed an unexpected high frequency of megakaryoblastic leukemias as well as erythroleukemias. As previously reported for ALL in infants, ANLL of infancy shows a similar heterogeneity regarding phenotypic and genotypic features.
Leukemia 1989 Oct
PMID:Phenotypic and genotypic heterogeneity in infant acute leukemia. II. Acute nonlymphoblastic leukemia. 277 87

Sera from 11 Japanese patients with hairy cell leukemia and 4B122, an anti-hairy cell serum produced by the authors, were surveyed by Western blot analyses for cross-reacting antibodies to human T cell leukemia virus (HTLV)-I and -II virions released, respectively, from Lma-66 and Mo-T cell lines. Sera from the majority of the patients showed positive reactions with p15, p19, and/or p24 of HTLV-I and with p21 and/or p22 or HTLV-II. 4B122 was weakly cross-reactive with HTLV-II but not with HTLV-I. These results militate against the involvement of HTLV-I or -II but may implicate a role by a cross-reacting, previously unrecognized retrovirus in the pathogenesis of hairy cell leukemia in Japanese patients.
Leukemia 1987 Apr
PMID:Cross-reacting antibodies to human T cell leukemia virus-I and -II in Japanese patients with hairy cell leukemia. 282 19

Leukemic cell chromosomal findings in 27 infants were analyzed. Among the 18 cases of acute nonlymphoblastic leukemia (ANLL), all but two were classified as monocytic or myelomonocytic. The remaining nine cases were acute lymphoblastic leukemia (ALL), seven lacking the common ALL antigen and two having cytoplasmic immunoglobulin (pre-B phenotype). Twenty-five cases (93%) had an abnormal karyotype, 21 (84%) being pseudodiploid. Chromosomal translocations were detected in 67% of the ANLL cases and in 78% of the ALL cases. Nonrandom chromosomal abnormalities included the t(9;11)(p21-22;q23) in three cases of monocytic leukemia, inversion of chromosome 16 in three cases of myelomonocytic leukemia with bone marrow eosinophilia, and t(4;11)(q21;q23) in one case of ALL. Chromosomal regions preferentially involved in infant leukemia included 11q23-25 (13 cases), 9p21-22 and 10p11-13. All but one of the 24 cases with chromosomal breakage or rearrangement had breakpoints that corresponded to known fragile sites, half of which were at 11q23-25, a finding that may have pathogenetic importance. The CALLA- or pre-B phenotype and the presence of chromosomal translocations in most infants with ALL provide a biological explanation for their poor prognosis.
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PMID:An analysis of leukemic cell chromosomal features in infants. 295 82

The human T-cell leukemia virus type-1 (HTLV-1) contains a unique pX region, which encodes the gene products p40 chi, p27 chi-III and p21 chi-III. p40 chi is required for transcriptional trans-activation, whereas p27 chi-III and p21 chi-III have no such function. Transfection of pX expression plasmids containing different combinations for the three gene products into cells integrated with HTLV-1 proviruses defective in pX expression revealed that both p40 chi and p27 chi-III are required for expression of the gag protein and accumulation of gag mRNA. These observations suggest that the pX product p40 chi activates transcription and p27 chi-III controls the level of gag mRNA by post-transcriptional modulation.
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PMID:The second pX product p27 chi-III of HTLV-1 is required for gag gene expression. 302 15


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