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

Phorbol ester-induced differentiation of human B-chronic lymphocytic leukaemic cells was found to be preceded by a rapid transient induction in expression of the c-jun proto-oncogene, which paralleled that of c-fos. Induced expression of c-myc but not of c-fos/c-jun proto-oncogenes was markedly higher in a proliferating variant leukaemic cell population compared with that seen in typical lymphocytic leukaemia cells. These data suggest that the c-fos/c-jun nuclear oncogenes play a role in induced differentiation, whilst c-myc is more important in the proliferative response of B lymphocytes.
 ...
PMID:Patterns of nuclear proto-oncogene expression during induced differentiation and proliferation of human B chronic lymphocytic leukaemia cells. 231 71

The administration of 1 mM sodium butyrate induced the phenotypic differentiation of human promonocytic leukemia U937 cells, as judged by the expression of cD11b and cD11c antigens, two differentiation-specific surface markers. At the same time, butyrate greatly induced the expression at the mRNA level of the vimentin gene. The increase in the level of this RNA started at 6 h of treatment and reached the maximum at Hour 24. Such an increase was caused at least in part by a stimulation in the rate of gene transcription, as suggested by transcription assays in isolated nuclei. Experiments in the presence of cycloheximide suggested that vimentin induction is probably a direct response to the action of butyrate, not mediated by the prior induction of other gene products. Unlike the case of vimentin, the levels of other RNAs, namely beta-actin, ornithine decarboxylase, and c-myc, were not enhanced, but they decreased at different times of treatment with butyrate. Finally, we observed that butyrate induced also the differentiation of HL60 cells, another human myeloid cell type. Nevertheless, the drug failed to stimulate the expression of vimentin in this cell line.
 ...
PMID:The induction of vimentin gene expression by sodium butyrate in human promonocytic leukemia U937 cells. 232 71

We have studied tumor necrosis factor alpha (TNF-alpha) for its capacity to induce differentiation and to modulate c-myc and c-fms protooncogene mRNA expression in fresh blasts from 10 patients with acute myeloblastic leukemia (AML). Bone marrow blast cells were grown in suspension cultures in the presence of 500 U/ml (62 ng/ml) of TNF-alpha for 7 days. Induction of differentiation was assessed by means of morphology, cytochemistry, immunophenotyping (CD11b, CD13, CD14, CD33), and nitroblue tetrazolium reduction. In all cases, exposure of leukemic blasts to TNF-alpha resulted in phenotypic changes consistent with induction of differentiation, although a marked variability in degree and type of response was observed. The majority of cases developed monocytic morphology and showed significant increases (chi 2 test, p less than 0.05) in phagocytic activity and/or expression of ANAE and myelomonocytic differentiation antigens (CD11b, CD14). TNF-alpha reduced c-myc mRNA level over a period of 24 hr in four of six cases studied: the two cases with no down-regulation were the least responsive in terms of myelomonocytic differentiation. These results confirm those obtained with leukemic cell lines, suggesting that TNF-alpha can induce differentiation of fresh AML blasts, mainly toward the monocytic lineage, and that induction of differentiation seems to be closely linked to down-regulation of c-myc mRNA expression over the first 24 hr rather than to attenuation of cellular proliferation per se.
Leukemia 1990 Jun
PMID:Tumor necrosis factor alpha down-regulates c-myc mRNA expression and induces in vitro monocytic differentiation in fresh blast cells from patients with acute myeloblastic leukemia. 235 42

The present studies demonstrate that dimethylsulfoxide (DMSO) treatment of human U-937 myelomonocytic leukemia cells is associated with induction of monocytic differentiation. The DMSO-induced U-937 monocytic phenotype was associated with 1) growth inhibition, 2) loss of clonogenic survival, 3) increases in alpha-naphthyl acetate esterase (NSE) staining, and 4) increases in cell surface expression of the monocyte marker Mac-1. DMSO treatment of U-937 cells was also associated with down-regulation of c-myc and c-myb gene expression as well as with increases in tumor necrosis factor (TNF) mRNA levels. The results further demonstrate that induction of U-937 monocytic differentiation by DMSO is accompanied by increases in phospholipase A2 activity. Moreover, this stimulation of phospholipase A2 was sensitive to dexamethasone. We therefore studied the effects of dexamethasone on DMSO-induced differentiation of U-937 cells. Although dexamethasone had no effect on growth inhibition or loss of clonogenic survival by DMSO, this glucocorticoid blocked increases in NSE staining and cell surface Mac-1 expression. Dexamethasone also had no effect on the down-regulation of c-myc and c-myb expression but blocked the reappearance of c-myb transcripts after 6 hr of DMSO treatment. Finally, dexamethasone inhibited DMSO-induced increases in TNF gene expression. Taken together, the results demonstrate that dexamethasone inhibits multiple characteristics, including the stimulation of phospholipase A2 activity, associated with DMSO-induced monocytic differentiation of U-937 cells.
 ...
PMID:Effects of dexamethasone on induction of monocytic differentiation in human U-937 cells by dimethylsulfoxide. 240 76

The McDonough strain of the feline sarcoma virus contains a transforming gene (v-fms) which contains partial nucleotide homology with proto-oncogenes encoding tyrosine kinases. One of the v-fms-encoded products, gp140fms, is a cell surface transmembrane glycoprotein that may function as a growth factor receptor. Although c-fms transcripts have been detected in placental trophoblasts and normal human bone marrow, the role of the c-fms gene product is unknown. We now report that induction of monocytic, but not granulocytic, differentiation of human HL-60 leukaemic cells is associated with expression of c-fms, preceded by that of c-myc and c-fos. Because c-fms transcripts are also detectable in peripheral blood monocytes and in blasts from certain patients with myelomonocytic leukaemia, the c-fms gene product may play a role in monocytic differentiation.
 ...
PMID:Expression of the c-fms proto-oncogene during human monocytic differentiation. 240 50

The relative abundances of c-myc-related RNA in the total cellular RNA of peripheral blood leukocytes from 36 patients with leukaemia have been compared with those in normal peripheral blood leukocytes and in HL60 cells. Varying amounts of c-myc-related RNA were found in RNAs from leukocytes from patients with ANLL, CGL and ALL. High concentrations (comparable with that in HL60 cells) were found in 13 (36%) of the leukaemias and lower, but still significant, concentrations in a further 15 (42%). Low concentrations of c-myc-related RNA, comparable to that in normal leukocytes, were found in 2 of 8 CGLs, 1 of 12 ANLLs, and 5 of 5 CLLs. DNAs from 11 leukaemia patients' leukocytes, in which c-myc-related RNA concentrations ranged from very high to very low, were examined for rearrangements and/or amplification of the c-myc gene. No rearrangements were detected, and the small degree of amplification (2- to 4-fold at most) found was not correlated with increased levels of c-myc RNA. There was, however, a noteworthy (though incomplete) correlation between elevated levels of c-myc-related RNA and the occurrence of higher proportions of blast cells in leukocyte populations from leukaemic patients. It is suggested that high levels of c-myc-related RNA in a population of peripheral blood leukocytes indicate the presence of a high proportion of leukaemic leukocytes that are maturation-arrested at early stages of development.
 ...
PMID:Expression of the myc gene locus in populations of leukocytes from leukaemia patients and normal individuals. 242 11

We studied the effects of gamma interferon (IFN-gamma) on HLA class I gene expression, differentiation, and proliferative capacity of K562 human leukemia cells. In the uninduced state, K562 cells show little or no class I gene expression but actively express the erythroid-specific gamma-globin gene as well as genes associated with cell proliferation, including the transferrin receptor, c-myc, and alpha-actin genes At both the surface protein and mRNA levels, IFN-gamma induces class I and beta 2-microglobulin gene expression, but does not alter the expression of the gamma-globin, transferrin receptor, c-myc, or alpha-actin genes. A 10-fold maximal induction of both class I surface protein and mRNA occurs at 48 h and is reversible upon withdrawal of IFN-gamma from the culture medium. In vitro nuclear run-on transcription assays were performed to directly establish that IFN-gamma exerts an early effect at the level of transcription, with maximal transcription rates occurring within 4 h. The difference between the time course of transcription induction and that of mRNA accumulation suggests that the regulation of class I gene expression in this human leukemic cell line also involves posttranscriptional mechanisms. Measurements of cell proliferation rates and cell cycle distribution, as well as the reversibility of the effects of IFN-gamma, demonstrate that the selective induction of class I genes in these cells occurs in the absence of differentiation.
 ...
PMID:Gamma interferon and 5-azacytidine cause transcriptional elevation of class I major histocompatibility complex gene expression in K562 leukemia cells in the absence of differentiation. 243 Dec 85

RNA transcript levels of the protooncogenes c-myc, c-fos, and c-fms were measured in bone marrow cells obtained from patients with acute myelocytic leukemia at diagnosis or in complete remission. As controls, normal bone marrow cells were studied. The c-myc RNA levels are significantly higher in acute myelocytic leukemia cells at diagnosis than in remission or in normal marrow cells. In most instances the high c-myc RNA levels are a reflection of the high proportion of immature cells present in leukemic marrows. The bone marrow cells of several patients contain extremely high levels of c-myc RNA, levels which cannot be accounted for by the proportion of immature cells present in the bone marrow. The leukemic cells of patients with morphologically indistinguishable leukemias manifest different patterns of c-myc, c-fos, and c-fms expression. This observation is consistent with differences in behavior of leukemic cells even among patients with the same French-American-British type of leukemia. The normal-appearing bone marrow cells of some acute myelocytic leukemia patients in complete remission differ from normal bone marrow cells in having slightly higher c-myc RNA levels, as well as in the pattern of expression of c-fos and c-fms. The possible use of protooncogene expression patterns to subdivide the French-American-British categories of acute myelocytic leukemia into subtypes with greater prognostic significance is discussed.
 ...
PMID:Expression of the protooncogenes c-myc, c-fos, and c-fms in acute myelocytic leukemia at diagnosis and in remission. 243 29

Several oncogenes have been reported to be expressed in normal and malignant hematopoietic cells. Since these studies have almost exclusively been done by Northern and dot blot hybridization techniques using mixed populations of cells, any conclusions concerning quantitative changes in gene expression are difficult to document. We have developed a rapid and sensitive RNA-in situ hybridization technique permitting detection of as few as five copies of mRNA per cell. Using this technique we have studied the expression of two genes, c-myc and c-sis, in acute leukemia patients as well as hematologically normal individuals. We have found that expression levels of myc and often sis are higher (greater than 5-fold) in hematopoietic cells obtained from leukemia patients than in normal hematopoietic cells. In regenerating marrow, there is a dramatic increase in the frequency of cells expressing myc at the level of five to 10 copies without the presence of any cells expressing myc at the high levels found in acute leukemia. This is completely different from leukemic remission marrow in which we find a subpopulation of cells which express myc at very high levels. At this time, the leukemic origin of this abnormal cell population is likely because of the close correlation we find between gene overexpression and leukemic phenotype as identified by double-labeling experiments. It appears that gene overexpression may be a more sensitive or an earlier marker for leukemic cells and that such an assay could be used in the detection of residual disease.
Leukemia 1988 Jan
PMID:myc and sis expression in acute myelogenous leukemia. 244 56

Physiological inducers of myeloid cell growth and differentiation were used to simultaneously analyze the expression of the proto-oncogenes c-myc, c-myb, c-fos, c-fes and c-fms during normal myelopoiesis, where growth is coupled to differentiation, as compared with that in leukemia, where growth has been uncoupled from differentiation as well as upon suppression of the leukemic phenotype via induction of differentiation and growth arrest. Proto-oncogene expression was also used as a tool to dissect the growth to differentiation developmental cascade. Myeloid cell growth was correlated with high c-myc and c-myb RNA levels, decreasing to undetectable levels in terminally differentiated cells. No c-myc RNA was detected in normal myeloid progenitors induced for differentiation without growth, using media conditioned by mouse granulocytes (GCM), indicating that c-myc may play either no role or an inhibitory one in differentiation. RNA levels of the proto-oncogenes c-fos, c-fes and c-fms were undetectable in normal or M1 differentiation inducible (D+) leukemic myeloblasts, and were stably induced upon stimulation of the normal precursors for growth and differentiation, with highest levels at the time when most of the cells had undergone terminal differentiation. Only c-fes RNA was induced upon M1D+ differentiation. It was also shown to be induced upon induction of differentiation without growth in normal myeloid precursors. Using c-myc and c-myb RNA suppression as molecular markers for induction of M1D+ differentiation, the existence of myeloid differentiation factor(s), distinct from myeloid growth factors, has been demonstrated. Such differentiation inducing activity was found in media conditioned by mouse lungs or granulocytes, and was induced in normal myeloid precursors by the myelopoietic growth factors IL3, GM-CSF, G-CSF, and M-CSF. Taken together, the results of this study enhance and add to previous work to better correlate the expression of the proto-oncogenes myc, myb, fes, fos and fms with several parameters of normal and abnormal myeloid cell growth and differentiation. The results indicate that the normal myeloid growth to differentiation developmental cascade entails a mechanism whereby myeloid growth factors induce myeloid differentiation factors, subsequently suppressing c-myc and c-myb RNA expression, leading to the induction of differentiation and growth arrest, including early accumulation of c-fes RNA followed by accumulation of c-fos and c-fms RNAs. It was also indicated that this cascade is impaired in leukemia.
 ...
PMID:Proto-oncogene expression and dissection of the myeloid growth to differentiation developmental cascade. 247 Nov 31


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>