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

Prolonged exposure to 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] of 2 sublines (AB-2 and AB-26) of human promyelocytic HL 60 leukemia cells produced increased adherence of the cells to the culture substratum. Advantage was taken of this property to separate physically a population of cells highly enriched in macrophage-like forms. When these differentiated cells were placed in culture medium free of 1,25(OH)2D3, there was a rapid reversal of the features of the differentiated phenotype, monitored by the loss of alpha-naphthyl butyrate esterase activity and the loss of adherence to the substrate. The reversal was accompanied by the resumption of normal rates of DNA synthesis, mitosis, and reaccumulation of c-myc and c-myb transcripts. The levels of transcripts of oncogenes c-fos and c-fms, which became abundant in the phenotypically differentiated cultures, declined along with the loss of adhesiveness and reversion to more primitive myeloblastic forms. These changes in proto-oncogene expression became evident before cell proliferation resumed, thereby excluding the diluting effect of the outgrowth of undifferentiated cells. It is concluded that in this system there is no firm commitment to terminal, as opposed to early, differentiation in the great majority of the cells and that the expression of the monocytic maturation-associated genes c-fos and c-fms is down-regulated when macrophage-like cells dedifferentiate. This strengthens the case for an association between macrophage differentiation and the expression of oncogenes c-fos and c-fms.
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PMID:Changes in proto-oncogene expression associated with reversal of macrophage-like differentiation of HL 60 cells. 347 50

The expression of transcripts of the c-myb and c-myc protooncogenes and the interleukin 2 receptor (IL-2R) gene in human T cells infected with human T-cell leukemia virus type 1 (HTLV-1) after exposure to interleukin 2 (IL-2) were examined. Infection with HTLV-1 is known to be associated with constitutive expression of IL-2R, although infected cells do not require IL-2 for growth. Northern blot analysis showed that expression of the mRNAs of the c-myb, c-myc, and IL-2R genes were markedly increased by addition of IL-2 into the cultures, indicating that IL-2R transduced signals for gene expression in these cells as in normal T cells. Studies on distinct HTLV-1-infected T cell clones that differed in numbers of high-affinity IL-2R, showed that the extents of increase in mRNA expression by IL-2 were correlated with the number of high-affinity IL-2R. This correlation was confirmed by demonstration that the levels of mRNA expression were proportional to the numbers of IL-2-bound high-affinity but not low-affinity receptors. Thus, the signals induced by IL-2 for gene expression may be through high-affinity IL-2R.
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PMID:High affinity interleukin 2 receptors in HTLV-1-infected T cells can mediate signals for gene expression. 350 78

The structure and the expression of 11 cellular oncogenes (protooncogenes) were analyzed in primary cells from 20 acute lymphocytic (ALL) and 31 acute myelogenous (AML) leukemia patients. Neoplastic cells, obtained prior to initiation of therapy, were purified and classified, on the basis of both surface antigen pattern and morphology, into pre-B, B, and T ALL and M1-M5 AML. RNA was extracted and analyzed for expression of cellular oncogenes coding for nuclear proteins (c-myc, c-myb, c-fos), the beta-chain of platelet-derived growth factor (c-sis), growth factor receptors or related proteins (c-src, c-abl, c-fes, c-erbB), or putative intermediate transducers of mitogenic signals (c-Ha-ras, c-Ki-ras, c-N-ras). Quantitative analysis of total RNA was carried out by dot blot hybridization to specific cDNA or genomic probes. Number and size of transcripts were evaluated by blot hybridization of electrophoretically fractionated poly(A)+ RNA. Expression of c-myc and c-myb was detected in all leukemic cells at variable levels and was characterized by well-defined patterns within ALL subtypes. Conversely, significant levels of c-fos transcripts were detected only in myelomonocytic (M4) and monocytic (M5) leukemias. Among the "src-family," c-fes was expressed more in AML than ALL, and c-abl was expressed at variable but not elevated levels in all leukemia types. c-Ha-ras was uniformly expressed at low levels, as in non-neoplastic cells. c-Ki-ras transcription was detected only in T ALL; N-ras expression was barely demonstrable. The structure of these protooncogenes was not grossly modified, as evaluated by Southern analysis, except for c-myc rearrangement in B ALL. These studies indicate that cellular oncogene expression in specific subtypes of leukemic cells may relate to either the proliferative activity (c-myc, c-myb) or the differentiation state (c-fos) of the cells, or possibly to expression of receptors for putative hemopoiesis-related growth factors (c-fes, c-abl). Our data provide a basis for in-depth analysis of protooncogene expression in normal and neoplastic hemopoiesis.
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PMID:Expression of cellular oncogenes in primary cells from human acute leukemias. 352 May 70

Antiserum to a synthetic peptide that defines a hydrophilic region within the putative c-myb translation product was prepared in the rabbit. In lysates from exponentially growing ML-1, human myeloblastic leukemia cells, the antiserum ("anti-myb") reacted with five proteins of Mr 58,000, 75,000, 85,000, 90,000 and 105,000. Of these, only p75 and a trace of p85 were detected, by immunoblotting, in extracts derived from ML-1 cell nuclei. The proteins p58, p75 and p90 were present in readily detectable amounts only in the relatively immature myeloid cell lines ML-1 and HL-60, whereas in the more mature myeloid cell line THP-1 and in the lymphoid line BALL-1 only traces of these proteins were found. p85 and p105 were detected in lysates from all cell lines tested, including myeloid and lymphoid leukemia cells and mouse 3T3 cells. In lysates from ML-1 cells induced to differentiate to monocyte/macrophages or to granulocytes, the concentrations of p58 and p75 decreased in parallel with the cell population moving to maturity; in completely mature populations these two proteins were no longer detectable. In ML-1 cells arrested in G1 by serum depletion, the amount of p58 and p75 and to a smaller extent that of p90 was decreased, whereas the concentration of p85 and p105 remained unchanged. In nuclei from exponentially growing ML-1 cells, the antiserum or its derived immunoglobulin fraction ("anti-myb IgG") inhibited mRNA transcriptional activity by 30%. DNA synthesis was not affected. In contrast, in nuclei from differentiated ML-1 cells, the mRNA transcriptional activity was not significantly inhibited by anti-myb IgG. Similarly, in nuclei from ML-1 cells arrested largely in G1 by serum depletion for 2 days, mRNA transcriptional activity was inhibited by only 11%. Upon supplementation with serum, the mRNA transcriptional activity inhibitable by anti-myb IgG increased in parallel with the increasing rate of cell growth. The difference in total mRNA transcriptional activity observed in nuclei from cells of different growth rate was accounted for by the difference in transcriptional activity inhibitable by anti-myb IgG.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Inhibition of messenger RNA transcriptional activity in ML-1 human myeloblastic leukemia cell nuclei by antiserum to a c-myb-specific peptide. 354 99

We and other investigators have previously reported our findings on oncogene expression in human leukemia in an attempt to study the possible involvement of these genes in the leukemic state. An important shortcoming of these studies has been the lack of information on the expression of these genes in normal hematopoietic cells. To address this question we analyzed both the transcript size and level of expression of six oncogenes in fresh hematopoietic cells obtained from hematologically normal individuals and compared the results to those found in fresh samples obtained from patients with various forms of leukemia (acute myelogenous leukemia, acute lymphocytic leukemia, and chronic myelogenous leukemia). We found low level expression of c-myc, c-myb, c-fes, and c-raf in normal bone marrow in sharp contrast to the high levels of expression found in some forms of leukemia. C-fos was highly expressed in both normal bone marrow and certain leukemias. We were unable to detect c-sis expression in our normal samples. With the exception of c-fes, there was no variation in transcript size when comparing normal and leukemic samples. Having defined the transcript sizes and levels of expression for these proto-oncogenes in normal hematopoietic cells, we know that aberrant transcript size for the genes we have studied is not a common event in leukemias. The levels of expression, however, vary widely between normal hematopoietic cells and leukemia as well as between different types of leukemia.
Leukemia 1987 Aug
PMID:Proto-oncogene expression in human normal bone marrow. 366 72

Avian myeloblastosis virus (AMV), like other acute transforming viruses, arose by recombination between its helper virus and host cellular sequences. The latter sequences, termed v-myb, are responsible for the oncogenic properties of the virus. AMV causes acute myeloblastic leukaemia in chickens and transforms a specific class of haematopoietic cells in vitro, but does not induce morphological transformation of cultured fibroblasts, suggesting that only a restricted target-cell population is responsive to its transforming gene product. The normal cellular counterpart of v-myb, c-myb, is highly conserved and is present in all vertebrate and some invertebrate species examined. DNA rearrangements and altered expression of the myb oncogene have been reported in mouse lymphoid tumours and human myeloid and colon tumours. The mechanism of activation of the cellular proto-oncogenes is thought to involve the structural alteration of the coding regions that result in either the synthesis of an altered gene product or the enhanced expression of a proto-oncogene caused by alterations in its regulatory elements. To distinguish between these two mechanisms, we have cloned and sequenced the chicken c-myb complementary DNA and compared it with that of v-myb sequences. We demonstrate that during the transduction of the cellular sequences and/or viral passage a substantial portion of the coding region of the c-myb gene has been lost from both the 5' and 3' ends, resulting in the generation of a truncated gene product that mediates the transforming function of the virus.
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PMID:Nucleotide sequence of chicken c-myb complementary DNA and implications for myb oncogene activation. 375 48

Rearrangement in the c-myb locus of each of four independently derived BALB/c plasmacytoid lymphosarcoma (ABPL's) is due to the insertion of a defective Moloney murine leukemia virus (M-MuLV) into a 1.5-kilobase-pair stretch of cellular DNA at the 5' end of the v-myb-related sequences. This retroviral insertion is associated with abnormal transcription of myb sequences and probably represents a step in the neoplastic transformation of ABPL cells.
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PMID:Activation of the c-myb locus by viral insertional mutagenesis in plasmacytoid lymphosarcomas. 609 60

The relationship of oncogene expression to proliferation and differentiation has been examined in a line of human myeloblastic leukemia (ML-1) cells. Proliferating leukemic cells were found to express a 4.3-kilobase cellular homologue (c-myb) of the transforming sequence of avian myeloblastosis virus. A rapid decline in the expression of this transcript was seen in cells induced to differentiate with 12-O-tetradecanoylphorbol-13-acetate. The level of c-myb RNA was decreased by greater than 50% as early as 3 hr after 12-O-tetradecanoylphorbol-13-acetate exposure, and at 8 to 72 hr the reduction was greater than or equal to 4-fold. Subsequent to the decrease in oncogene expression at 3 hr, DNA synthesis began to decline; by 24 hr, cell proliferation had ceased. At this time, monocyte- and macrophage-like cells were beginning to emerge. These findings demonstrate that c-myb is expressed during ML-1 cell proliferation and declines prior to the loss of DNA synthesis that accompanies the differentiation process.
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PMID:Early decline in c-myb oncogene expression in the differentiation of human myeloblastic leukemia (ML-1) cells induced with 12-O-tetradecanoylphorbol-13-acetate. 619 73

The genome of avian leukemia virus E26 shares homology with v-myb, the oncogene of avian myeloblastosis virus, and encodes a protein with an Mr of 135,000. Analyses of tryptic oligopeptides show that this protein is related to the proteins encoded by gag (Pr76gag) as well as v-myb (p45v-myb[AMV] ) and c-myb (p75c-myb). We found no evidence for the existence of additional myb-related proteins or subgenomic species of myb-related RNA in myeloblasts transformed by strain E26.
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PMID:Neoplastic transformation by E26 leukemia virus is mediated by a single protein containing domains of gag and myb genes. 619 15

It is widely thought that c-onc genes (or proto-oncogenes)--the cellular progenitors of retroviral transforming genes--are involved in cellular differentiation and/or proliferation. Such ideas originate primarily from the ability of v-onc genes and 'activated' c-onc genes to induce uncontrolled cellular proliferation, and their capacity to arrest or interfere with differentiation processes in some systems. Haematopoietic cell populations provide additional support for these ideas as c-myb RNA is present in cell lines corresponding to immature, but not mature, cell types, and elevated levels have been found in tissues that are active in haematopoiesis. We have now examined the effects of induced differentiation on c-onc gene expression in a murine myeloid leukaemia cell line, WEHI-3B ('D+' subline). Our results show that the expression of c-myb and c-myc, at the level of transcription, decreases only at late stages in the monocytic differentiation of WEHI-3B cells, while expression of c-fos increases markedly. We suggest that c-myb and c-myc do not themselves control myeloid differentiation, but that they function in the maintenance of the proliferative state of myeloid cells. The induction of c-fos may reflect its role in some macrophage-specific functions.
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PMID:Expression of myb, myc and fos proto-oncogenes during the differentiation of a murine myeloid leukaemia. 620 76


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