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)

Primitive cells defined as long-term culture initiating cells (LTCIC) and blast colony-forming cells (Bl-CFC) bind to cultured stromal layers, but cells at later stages of maturation [granulocyte-erythroid-macrophage-monocyte colony-forming cells (GEMM-CFC) granulocyte-macrophage (CM-CFC) and erythroid burst-forming units (BFU-E)] do not. The precise relationship between the LTCIC and Bl-CFC is not known and this study was undertaken to determine their relative positions in the haemopoietic hierarchy. We have defined the Bl-CFC population in terms of its density profile and antigenic phenotype and compared these characteristics with GM-CFC and BFU-E. The progenitor cell populations did not differ in density. The major phenotypic difference was seen using the myeloid monoclonal antibody S17-25 which reacted with fewer Bl-CFC than GM-CFC. Also, we have cytochemically analysed the cells in colonies derived from Bl-CFC. Our studies indicate that the Bl-CFC precede BFU-E and GM-CFC but not the LTCIC.
Leukemia 1992 Apr
PMID:Physical, phenotypic and cytochemical characterisation of stroma-adherent blast colony-forming cells. 158 97

The human factor-dependent leukemia cell line UCSD/AML1 contains the t(3;3) (q21;q26) characteristic of the syndrome of acute leukemia with high platelets. The human homologue of the murine leukemia oncogene evi-1 was recently localized to chromosome 3q24-3q28 and transcription of evi-1 is a frequent event in mouse-retrovirus-induced leukemias (17). To determine whether translocations near human 3q24 might induce similar genetic changes, we examined and compared evi-1 and c-myc expression and regulation in UCSD/AML1 cells. Steady-state evi-1 transcripts were detected in UCSD/AML1 and murine leukemia M1 cells, but were not present in HL60 or Namalwa human leukemia cells. Transcription assays showed the evi-1 gene was actively transcribed in UCSD/AML1, but not HL60 nuclei. Evi-1 transcript sizes and half-life were similar in UCSD/AML1 and human HEC-1B carcinoma cells which express evi-1 transcripts, but do not have abnormalities involving chromosome 3. An alternative splice site detected by polymerase chain reaction was present in transcripts from both cell lines. Regulation of evi-1 RNA in UCSD/AML1 cells was similar to that of actin transcripts in response to cycloheximide or phorbol-ester-induced macrophage differentiation. After withdrawal of granulocyte/macrophage colony-stimulating factor (GM-CSF), evi-1, actin, and histone H3 transcripts declined in concert with exit from the cell cycle. Minor differences in rates of recovery were noted for these three genes after GM-CSF restimulation. In contrast, c-myc was expressed at high levels in UCSD/AML1 cells and showed evidence for specific regulation in response to cycloheximide, phorbol ester, and GM-CSF withdrawal and restimulation. These studies suggest the 3q translocation in UCSD/AML1 cells is associated with evi-1 transcription and expression of a potential transforming gene. In contrast to c-myc, evi-1 expression is minimally altered by biologically active chemicals or growth factor stimulation.
Leukemia 1992 May
PMID:Expression and regulation of the evi-1 gene in the human factor-dependent leukemia cell line, UCSD/AML1. 159 10

Tumor necrosis factor-alpha (TNF-alpha), produced predominantly by activated monocytes/macrophages, inhibits leukemic cell growth and may contribute to a graft-versus-leukemia effect after marrow transplantation. We examined the recombinant cytokines interferon (IFN)-alpha, IFN-gamma, granulocyte- macrophage colony-stimulating factor (GM-CSF), and macrophage colony-stimulating factor (M-CSF), alone or in combination, for their ability to induce monocytes from normal donors and patients after marrow grafting to express TNF-alpha mRNA and secrete TNF-alpha bioactivity. Monocytes were isolated from peripheral blood by Percoll separation of E-rosette-negative cells, and cultured with cytokines under non-adherent, endotoxin-free conditions. TNF-alpha transcripts were undetectable in freshly isolated monocytes from normal donors. Only the combination of IFN-gamma/GM-CSF was consistently capable of inducing substantial TNF-alpha mRNA transcript levels and protein secretion. Levels of TNF-alpha transcripts induced by IFN-gamma/GM-CSF were maintained for at least 36 h, in contrast to lipopolysaccharide (LPS) stimulation which caused TNF-alpha mRNA levels to peak after 2 h and decline rapidly thereafter. IFN-gamma/GM-CSF was also capable of inducing a prolonged (at least 48 h) secretion of TNF-alpha bioactivity. In contrast, greater than 80% of the total TNF-alpha bioactivity secreted by LPS-stimulated monocytes was secreted in the first 8 h. When monocytes were incubated with IFN-gamma alone ('priming'), washed and then exposed to GM-CSF, both TNF-alpha mRNA expression and TNF-alpha protein production occurred.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of tumor necrosis factor-alpha production and gene expression in monocytes. 161 21

Acute myelomonocytic leukemia develops in 10-30% of irradiated (300 rad) SJL/J mice, after a lag period of around one year. Additional treatment with dexamethasone shortly after irradiation increased leukemia incidence up to 50%. Experiments were conducted in order to demonstrate the existence of preleukemic cells in irradiated mice and to explore the possible role of dexamethasone, cyclophosphamide, and different hemopoietic growth factors on their promotion to overt leukemia. Transplantation of bone marrow cells from mice exposed to 300 rad plus dexamethasone into appropriate recipients, performed 4-5 months after leukemogenic treatment, resulted in acute myeloid leukemia (AML) development of donor origin in 70% of the recipients. Transfer of fractionated preleukemic bone marrow showed that the highest AML incidence developed in the recipients of fractions enriched in early hemopoietic precursors. The promoting effect of dexamethasone on preleukemic cells was confirmed by demonstrating its similar coleukemogenic effect whether administered within several hours or 130 days after radiation. Treatment with cyclophosphamide shortly after radiation could not replace the dexamethasone effect but was found to be complementary to the coleukemogenic effect of dexamethasone. Early administration of hemopoietic growth factors (starting 14 days after radiation and dexamethasone) showed that colony-stimulating factor (CSF) 1 increased the AML incidence (75%) and reduced its latency. Treatment with recombinant granulocyte-CSF (rG-CSF) had a reduced effect and recombinant granulocyte-macrophage CSF (rGM-CSF) had no promoting effect. However, administration of different factors several months after the leukemogenic treatment revealed that rGM-CSF increased AML incidence (75%) and shortened its latency, whereas rG-CSF and CSF-1 had no effect. In contrast, the late administration of recombinant interleukin 6 reduced AML incidence significantly (23%). The present results indicate that murine radiation induced AML is a multiphase process involving radiation induced preleukemia that can be promoted by different treatments.
Leukemia 1992 Jul
PMID:Initiation and promotion in radiation-induced myeloid leukemia. 162 87

Successful engraftment of autologous bone marrow depends on preserving the viability of stem cells during cryopreservation. While several techniques for effective bone marrow and peripheral blood stem cell collection and processing have been reported, little is known about the effect of the duration of cryopreservation on stem cell viability in humans. We reviewed, retrospectively, the engraftment data of 33 patients with leukemia treated at Brigham and Women's Hospital, Boston and the European Bone Marrow Transplant Group from 1981-1989 who received stem cells cryopreserved for greater than or equal to 2 years. Data on cryopreservation methods are available in 18 of 33 patients. In all cases, stem cells were frozen in liquid nitrogen with a programmed freezer and stored at or below -140 degrees C. The median duration of cryopreservation was 2.8 years (range 2-11 years). Thirty of 32 (94%) evaluable patients achieved granulocyte counts greater than 500 x 10(6)/l (median 23 days; range 10-119 days); 26 of 32 (74%) evaluable patients achieved platelets greater than 50 x 10(9)/l (median 30 days; range 19-128 days) while 22/32 (69%) patients achieved platelets greater than 100 x 10(9)/l (median 45 days; range 20-328 days). This report demonstrates that human stem cells cryopreserved for up to 11 years are capable of engrafting. Stem cells may be stored for prolonged periods and used for transplantation in patients harvested prior to pelvic irradiation or alkylating agent therapy.
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PMID:Long-term cryopreservation of human stem cells. 162 34

In Philadelphia chromosome (Ph1)-positive acute lymphoblastic leukemia (ALL), some cytogenetic studies have suggested clonal derivation from a multipotential stem cell. The role of the product of the chimeric gene, P190, is not, however, well understood. We examined the expression of P190-type bcr/abl in single hematopoietic colonies obtained at various clinical stages of a patient with Ph1-positive ALL, using the polymerase chain reaction (PCR). Seven out of 58 colonies examined expressed P190-type bcr/abl. Five out of seven colonies were granulocyte/macrophage (GM) colonies and two were erythroid colonies. The cell lineages of these colonies were confirmed by testing for the expressions of the myeloperoxidase (MPO) gene in the GM colonies and the beta-globin gene in the erythroid colonies. These results suggest transformation of multipotential stem cell in this patient and confirm that expression of the P190-type bcr/abl fusion gene permits stem cell differentiation leading to Ph1-positive ALL.
Leukemia 1992 Aug
PMID:P190-type bcr/abl expressed in myeloid colonies in a patient with Ph1-positive acute lymphoblastic leukemia. 164 Jul 30

In this study we demonstrate that tumor necrosis factors (TNF alpha and TNF beta) are potent modulators of the in vitro proliferation of human AML cells. Blast cells from 11 cases of acute myeloblastic leukemia (AML) were incubated with recombinant TNF alpha or TNF beta in serum-free 3H-TdR uptake and colony culture systems in the presence or absence of recombinant interleukin-3 (IL-3), granulocyte macrophage colony-stimulating factor (GM-CSF), G-CSF, or M-CSF. Depending on the supplemented CSF, TNF could upregulate or suppress AML blast proliferation. Enhancement of AML growth by TNF was observed in the presence of IL-3 (in 9 of 11 cases in 3H-TdR assay; 6 of 9 cases in colony assay) and GM-CSF (in 8 of 11 cases in 3H-TdR assay; 4 of 9 cases in colony assay). In certain cases in which IL-3 or GM-CSF alone was unable to induce proliferative responses of AML cells, the simultaneous addition of TNF elicited colony growth and DNA synthesis suggesting a synergistic action between TNF and IL-3 or GM-CSF. In contrast, TNF suppressed G-CSF-induced growth (9 of 10 cases in 3H-TdR assay; 5 of 6 cases in colony assay). TNF could also stimulate DNA synthesis (in 2 of 11 cases) or colony formation (in 2 of 9 cases) in AML cultures without the addition of other growth factors. Experiments with neutralizing antibodies and specific radioimmunoassays for individual CSFs showed that the synergistic and antagonistic effects of TNF on AML growth could not be attributed to a release of one of these CSFs by the AML cells. The opposing consequence of exposure of AML blasts to TNF are of interest in view of our understanding of the pathophysiology of AML growth and the in vivo application of recombinant cytokines in AML patients.
Leukemia 1990 Jan
PMID:Modulation of colony stimulating factor-(CSF) dependent growth of acute myeloid leukemia by tumor necrosis factor. 168 38

We evaluated the effects of recombinant human granulocyte colony stimulating factor (rhG-CSF) and granulocyte-monocyte colony stimulating factor (rhGM-CSF) on the in vitro proliferative, differentiative, and regenerative responsiveness of marrow cells from myelodysplastic syndrome patients (MDS) in comparison to those from normal individuals. Our studies showed decreased primary clonogenicity of myeloid (CFU-GM) and erythroid (BFU-E) hemopoietic progenitor cells from the MDS patients. rhGM-CSF had more potent stimulatory effects than rhG-CSF for MDS marrow CFU-GM growth; no enhanced cellular proliferation in the MDS patients was observed in liquid culture with either rhGM-CSF or rhG-CSF. Decreased myeloid clonal cell self-generation and/or recruitment occurred in the MDS patients upon exposure to either rhG-CSF or rhGM-CSF. rhG-CSF demonstrated more potent granulocytic differentiation effects than rhGM-CSF both for normals and MDS patients using marrow enriched for immature myeloid cells with lesser differentiation noted for MDS. Cytogenetic abnormalities, present with or without additional normal karyotypes in native marrow of four MDS patients, persisted after culture with rhG-CSF, indicating induced differentiation of both normal and abnormal clones. Although proliferative and differentiative effects were seen with both factors these data show MDS marrow cells in vitro to have predominantly differentiative responsiveness to rhG-CSF and proliferative responsiveness to rhGM-CSF.
Leukemia 1990 Mar
PMID:Effects of recombinant human granulocyte colony stimulating factor and granulocyte-monocyte colony stimulating factor on in vitro hemopoiesis in the myelodysplastic syndromes. 169 Mar 18

One proposed therapeutic application of granulocyte colony-stimulating factor (G-CSF) is in differentiation induction therapy of myelodysplastic states (MDS) or acute myeloid leukemia (AML). G-CSF however has a substantial growth including effect which limits its potential as a differentiation inducing agent. We have therefore made a systematic search for agents which might restrain the proliferative effects of G-CSF whilst retaining the differentiation stimulus. Of all the agents we have tested on human bone marrow progenitor cells: (6-thioguanine, all-trans retinoic acid, vincristine, recombinant human alpha-2b and gamma-interferon) only the latter abolished the stimulation of cell growth and retained, or possibly increased, the differentiation effect of G-CSF. The antiproliferative drugs 6-thioguanine and vincristine both antagonized the neutrophil-granulocyte differentiation inducing action of G-CSF. Retinoic acid and alpha-2b interferon both had weak effects on proliferation and failed to enhance differentiation. These results suggest that it may be possible, by combining G-CSF with a suitable second agent, to utilize its substantial differentiation inducing effect without incurring the potentially hazardous effects of increased leukemic cell growth.
Leukemia 1990 Mar
PMID:Dissociation of the proliferation and differentiation stimuli of granulocyte colony-stimulating factor (G-CSF). 169 Mar 19

The in vitro growth response of bone marrow and blood cells to granulocyte/macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF) was studied in 18 acute myeloid leukemia (AML) patients using semisolid and suspension cultures. In 80% of the cases growth of leukemic progenitor cells was stimulated by GM-CSF and/or G-CSF, as judged by colony or cluster formation. In acute promyelocytic leukemia [t(15;17)], G-CSF stimulated and maintained the leukemic progenitors only transiently but fully stimulated the residual normal granulocyte/macrophage colony-forming units (CFU-GM). In some cases of M2 and M4 leukemia, G-CSF enhanced markedly the production of mature but cytochemically abnormal neutrophils. In some cases of M1 leukemia, neither CSF stimulated leukemic progenitors but instead stimulated only residual normal granulopoiesis. Spontaneous colony formation was observed in 20% of cases and was correlated with high-grade leukemic growth in vivo and a poor response to chemotherapy. The differing effects of the CSFs upon leukemic cells and residual normal granulopoiesis may have some implications for the clinical use of GM-CSF and G-CSF to overcome infectious complications.
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PMID:In vitro growth response to G-CSF and GM-CSF by bone marrow cells of patients with acute myeloid leukemia. 169 Aug 27


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