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

N-ras oncogenes activated by point mutation have been frequently detected in various types of human leukemias. Analysis of a large number of leukemias revealed that activated N-ras oncogenes were observed preferentially in AML, AMoL, T-ALL and Null-ALL but rarely in CML and B-cell leukemia. These results suggest that N-ras oncogene plays an important role in human leukemogenesis. Activated N-ras oncogenes were also detected in myelodysplastic syndrome (MDS) that is considered to be a preleukemic disease. MDS patients bearing an activated N-ras oncogene frequently showed leukemic progression of the disease, suggesting that an activated N-ras oncogene can be a critical factor for prognosis of MDS patients. Thus, detection of an activated N-ras oncogene is useful for diagnosis, prognostic evaluation and therapeutic decision. Recently, we demonstrated that detection of the minimal residual disease by analysis of N-ras oncogene can lead to improvement of the remission rate in leukemias. Moreover, we made it possible to screen N-ras oncogene by a sensitive non-radioactive method. Our research procedure seems to be a good model for clinical application of the molecular biological technique.
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PMID:[Activation of ras oncogene in myelodysplastic syndrome and acute myelogenous leukemia]. 205 67

The human retrovirology opened its first chapter, 10 years ago, with the isolation and characterization of HTLV-I (Human T-cell leukemia virus, type I), a type C retrovirus, which was found to be etiologically linked first to adult T-cell leukemia and second to neurological disorders. Epidemiological data have indeed shown that patients who developed these diseases represent a small percentage of HTLV-I infected individuals living in restricted geographical areas. Experiments performed at molecular and cellular levels have revealed that HTLV-I plays an essential role in the initiation of the lymphoproliferative process. Indeed, viral particles deliver a mitogenic signal to human resting T lymphocytes. After proviral integration, two regulatory proteins--Tax and Rex--are controlling the replicative cycle of HTLV-I. The Tax protein trans-activates the proviral transcription and the Rex protein is essential in the synthesis of viral structural proteins. Furthermore, the Tax protein induces the transcription of several cellular genes involved in T-cell activation and proliferation. Studies are now aimed at identifying HTLV-I target cells among precursors of the T cell lineage and at unravelling the role of HTLV-I in the secondary events leading to leukemogenesis.
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PMID:Molecular and cellular events at the onset of the lymphoproliferative process induced by HTLV-I (human T-cell leukemia virus, type I). 205 28

An autocrine mechanism of proliferation may play a significant role in the leukemogenesis of adult T-cell leukemia, a mature T-cell malignancy caused by human T-lymphotropic virus type I (HTLV-I). To further delineate the role of HTLV-I and the interleukin 2 (IL2) system in the transformation process, human primary lymphocytes were infected by cocultivation with lethally X-irradiated MT2 cells in the presence or absence of human rIL2; the polymerase chain amplification reaction was used to examine quantitatively the expression of HTLV-I, IL2, and IL2R alpha mRNAs during early and late proliferation phases that displayed polyclonal (days 7 to 49) and oligoclonal (days 100 to 150) proviral integration, respectively. IL2 mRNA and IL2 activity were transiently expressed during the polyclonal phase but were undetectable at later time points. IL2R alpha mRNA expression remained at a constitutively high level throughout the examined time course. Viral transcripts were detectable at each time point. Expression of the tax-rex mRNA was inversely related to IL2 mRNA levels; it was low early in the polyclonal phase but increased 30-fold with the development of oligoclonality. In addition, paraformaldehyde-fixed HTLV-I-producing cells activated peripheral blood lymphocytes. These data suggest that HTLV-I activates human T lymphocytes. However, IL2 expression is transient, indicating a limited involvement of an IL2 autocrine growth loop in the transformation process. Lastly, another viral determinant, in addition to the trans activator tax, may be important in HTLV-I-induced T-cell proliferation.
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PMID:Temporal regulation of viral and cellular gene expression during human T-lymphotropic virus type I-mediated lymphocyte immortalization. 207 56

Previous studies have revealed marked differences in the incidence of leukemia between rats and mice exposed to 1,3-butadiene that do not appear to be readily explained on the basis of pharmacokinetics or metabolism. Chronic exposure to 1,3-butadiene results in a high incidence of thymic lymphoma in B6C3F1 mice that is not observed in Sprague-Dawley rats. Studies at the Chemical Industry Institute of Toxicology have focused on evaluating the potential of endogenous ecotropic retroviral background to influence susceptibility to 1,3-butadiene leukemogenesis. These studies have compared the pathogenesis and incidence of thymic lymphoma between B6C3F1 and NIH Swiss mice. Proviral ecotropic sequences are truncated in the NIH Swiss mouse, and the virus is not expressed. Chronic exposure to 1,3-butadiene (1250 ppm) for up to 1 year resulted in a fourfold difference in the incidence of thymic lymphoma between B6C3F1 and NIH Swiss mice. These results provide presumptive evidence for retrovirus involvement since NIH Swiss mice lack ecotropic viruses and appear to be relatively resistant to induction of lymphoma by 1,3-butadiene. Other explanations appear to be less likely in light of the fact that target organ toxicity has been determined to be virtually identical between the two strains during the preleukemic phase of 1,3-butadiene exposure.
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PMID:Studies on the mechanism of 1,3-butadiene-induced leukemogenesis: the potential role of endogenous murine leukemia virus. 216 11

The hybridization to a complementary RNA (cRNA) probe both in situ and in solution was used to assay tiny amounts of mRNA of the lactoferrin (LF) and myeloperoxidase (MPO) genes in normal bone marrow cells and in acute and chronic lymphoid leukemias. Evidence is reported that this technique is much more sensitive than the standard Northern blot technique. The LF mRNA was detectable in three of seven cases of acute lymphoblastic leukemia (ALL) and in three of seven cases of chronic lymphocytic leukemia (CLL). Four cases of ALL were also positive when tested with the MPO cRNA. It is apparent from these results that myeloid specific mRNA, different from MPO, may be detected in leukemic cells with lymphoid phenotype using a method more sensitive than the Northern blot technique. Whether or not the molecular events observed in these cell populations reflect events physiologically occurring rather than a deregulation of gene expression associated to leukemogenesis remains to be established.
Leukemia 1990 Oct
PMID:Detection of low abundance mRNA of myeloid specific genes in cells of acute and chronic lymphoid leukemias by cRNA hybridization. 217 Jul 80

All-trans retinoic acid (RA), the active metabolite of vitamin A, has recently been demonstrated to be an efficient alternative to chemotherapy in the treatment of acute promyelocytic leukemia (M3 subtype of the French-American-British cytological classification). Complete remission is obtained by inducing terminal granulocytic differentiation of the leukemic cells. To elucidate whether the effect of retinoic acid on the differentiation of M3 leukemic cells was related to any specific characteristics of its receptor, we analyzed the structure and expression of retinoic acid receptor (RAR) genes in 16 M3 patients. Abnormal RAR alpha transcripts were detected in 13 cases. In nine patients, the genomic DNA was analyzed by Southern blotting and evidence for a rearranged RAR alpha gene was found generated in four cases. Normal RAR transcripts and germline restriction fragments were found in samples from normal or other leukemic cells, suggesting that this alteration of the RAR alpha gene is specifically seen in M3 leukemias. These results suggest that alteration of the retinoic acid receptor alpha may be implicated in M3 leukemogenesis.
Leukemia 1990 Dec
PMID:The retinoic acid receptor alpha gene is rearranged in retinoic acid-sensitive promyelocytic leukemias. 217 2

Adult T-cell leukemia-lymphoma (ATL) is a unique T-cell leukemia-lymphoma that is closely associated with human T-cell leukemia virus type I (HTLV-I). HTLV-I is also associated with a benign disease, HTLV-I associated myelopathy. Main routes of the infection is through breast milk feeding from carrier mother to her baby, from carrier husband to wife, and by blood transfusion of carrier blood to recipient patients. The presence of anti-HTLV-I antibody is a definite sign of the carrier of HTLV-I, then screening of the antibody has been introduced with success to prevent the HTLV-I infection. Mechanism of leukemogenesis by the virus is not known. It is important to note that age-dependent occurrence of HTLV-I associated ATL can be simply described by a Weibull model. This suggests that ATL leukemogenesis might be the result of accumulation of numerous critical events, most likely somatic mutations, which are estimated to be five from the analysis. Although HTLV-I infection plays a primary role in the pathogenesis of ATL as an initiator, it may be only a prerequisite for accumulation of later events. The presence of HTLV-I negative ATL suggests that factor(s) other than HTLV-I infection may be involved in the leukemogenic process of ATL.
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PMID:[Human T-cell leukemia virus type I and adult T-cell leukemia-lymphoma]. 218 40

The diagnostic and prognostic value of specific cytogenetic abnormalities has been established for most recurrent translocations. For less frequent changes, we still need to collect more cases for determination of their clinical significance. Optimal treatment of leukemia with modern therapeutic strategies requires knowledge of the prognostic factors, and leukemic karyotype should be one of the variable features systematically evaluated in all trials. The molecular analysis of the specific translocation will considerably increase our understanding of the mechanism of leukemogenesis and provide us with new tools for diagnosis. Systematic collection and conservation of acute leukemic cells, cytogenetically and immunologically characterized, would greatly facilitate and accelerate these fundamental studies.
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PMID:Clinical relevance of cytogenetics in acute leukemia. 218 14

Monoclonal antibodies (McAbs) against a part of v-myb gene product were prepared for the detection of human c-myb gene product (p75c-myb). Western blotting analyses with these McAbs were performed on human leukemia-lymphoma cells. All T-cell lines were positive in p75c-myb expression. B-cell lines were variable, myeloid and erythroid cells were positive although the amount of expressed p75c-myb was less than the T-cell lines. Cells isolated from patients were positive in expression except for cells from acute myeloblastic leukemia with maturation (AML M2), acute hypergranular promyelocytic leukemia (AML M3) and erythroleukemia (AML M6) developed from myelodysplastic syndromes. Differences in p75c-myb expression seemed to depend upon the differentiation stage and distinctive lineage from which each cell line had been established. The p75c-myb expression in HL60 (acute promyelocytic leukemia cell line) showed remarkably high at logarithmic growth. When examined with HL60, p75c-myb expression significantly decreased during the differentiation induced by 12-O-tetradecanoylphorbol-13-acetate or retinoic acid. These results suggest that p75c-myb expression plays a crucial role in hematopoietic cell proliferation and differentiation and that multiple mechanisms including aberrant expression of p75c-myb is involved in leukemogenesis.
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PMID:p75c-myb expression in leukemia-lymphoma cells correlated with proliferation and differentiation. 218 45

Although determination of chromosomal abnormalities may be of limited usefulness for the diagnosis of leukemia, the recent advances in the molecular mechanism associated with chromosome aberration has been rapid. Chromosome translocation in Burkitt lymphoma and chronic myeloid leukemia was the most striking evidence for the oncogene activation. Other specific chromosome abnormalities for FAB-classified leukemias are also known. Translocated type of chromosome abnormalities between immunoglobulin or T-cell receptor genes and oncogenes may also affect the T and B-cell leukemogenesis. However, the role of trisomies found in human and experimental leukemias and the gene dosages had been thought to be most important until 1982, has not been unclear. Many types of phenotypically heterogeneous leukemias have been reported. t(4 ; 11) acute leukemia is one such leukemia which shows early B-cell and myelomonocytic nature. Heterogeneous leukemias have been called biphenotypic, hybrid and acute mixed leukemias. The terminology must be used the unified. Recent trials to use paraffin-fixed tissues and bone marrow smear for molecular analysis has been successfully reported. Basic analysis on the DNA degradation mechanism revealed the enzymatic activity might play an important role before the complete fixation.
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PMID:[Chromosome aberrations and genes in human and experimental leukemias]. 219 1


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