scholarly journals Structure and expression of genes of GM-CSF and G-CSF in blast cells from patients with acute myeloblastic leukemia

Blood ◽  
1988 ◽  
Vol 71 (1) ◽  
pp. 204-208 ◽  
Author(s):  
GY Cheng ◽  
CA Kelleher ◽  
J Miyauchi ◽  
C Wang ◽  
G Wong ◽  
...  
Keyword(s):  
Genomic Organization ◽  
Acute Myeloblastic Leukemia ◽  
Leukemic Cells ◽  
Hematopoietic Growth Factors ◽  
Gm Csf ◽  
Expression Of Genes ◽  
Blast Cells ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract The hematopoietic growth factors granulocyte/macrophage colony- stimulating factor (GM-CSF) and G-CSF, available as recombinant products, stimulate the growth in culture of blasts from patients with acute myeloblastic leukemia (AML). We used cDNA probes for each gene to study the genomic organization in blast cells of 22 patients and expression in the blast cells of 18 patients. Alteration in the structure of G-CSF (two instances) and GM-CSF (two instances) was found. In two patients in whom it was possible to study DNA from bone marrow obtained at remission, the new bands detected in the leukemic cells were not found. Fifteen of 18 patients showed no RNA expression of either growth factor. Both patients with GM-CSF abnormalities as seen by Southern analysis expressed an abnormally large GM-CSF message but no G-CSF messages. One patient with an abnormal Southern pattern with G-CSF expressed normal-sized G-CSF and GM-CSF messages. The biologic significance of these findings remains to be determined. Nonetheless, the abnormal Southern patterns may prove to be useful clonal markers in the study of AML.

scholarly journals Structure and expression of genes of GM-CSF and G-CSF in blast cells from patients with acute myeloblastic leukemia

Blood ◽  
1988 ◽  
Vol 71 (1) ◽  
pp. 204-208
Author(s):  
GY Cheng ◽  
CA Kelleher ◽  
J Miyauchi ◽  
C Wang ◽  
G Wong ◽  
...  
Keyword(s):  
Genomic Organization ◽  
Acute Myeloblastic Leukemia ◽  
Leukemic Cells ◽  
Hematopoietic Growth Factors ◽  
Gm Csf ◽  
Expression Of Genes ◽  
Blast Cells ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

The hematopoietic growth factors granulocyte/macrophage colony- stimulating factor (GM-CSF) and G-CSF, available as recombinant products, stimulate the growth in culture of blasts from patients with acute myeloblastic leukemia (AML). We used cDNA probes for each gene to study the genomic organization in blast cells of 22 patients and expression in the blast cells of 18 patients. Alteration in the structure of G-CSF (two instances) and GM-CSF (two instances) was found. In two patients in whom it was possible to study DNA from bone marrow obtained at remission, the new bands detected in the leukemic cells were not found. Fifteen of 18 patients showed no RNA expression of either growth factor. Both patients with GM-CSF abnormalities as seen by Southern analysis expressed an abnormally large GM-CSF message but no G-CSF messages. One patient with an abnormal Southern pattern with G-CSF expressed normal-sized G-CSF and GM-CSF messages. The biologic significance of these findings remains to be determined. Nonetheless, the abnormal Southern patterns may prove to be useful clonal markers in the study of AML.

scholarly journals Interleukin-6 enhances growth factor-dependent proliferation of the blast cells of acute myeloblastic leukemia

Blood ◽  
1988 ◽  
Vol 72 (2) ◽  
pp. 823-826 ◽  
Author(s):  
T Hoang ◽  
A Haman ◽  
O Goncalves ◽  
GG Wong ◽  
SC Clark
Keyword(s):  
Interleukin 6 ◽  
Bone Marrow Cells ◽  
Acute Myeloblastic Leukemia ◽  
Gm Csf ◽  
Normal Bone ◽  
Blast Cells ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Stimulation Of

Abstract The effects of recombinant interleukin-6 (IL-6) on the proliferation of blast precursors present in the peripheral blood of patients with acute myeloblastic leukemia (AML) was investigated. IL-6 had little effect by itself; however, it synergized with granulocyte macrophage colony- stimulating factor (GM-CSF) and interleukin-3 (IL-3) in the stimulation of AML blast colony formation. Responsiveness of blast progenitors to IL-6 was heterogeneous. On normal bone marrow cells the same synergy was observed on granulocyte and monocyte precursors (GM-CFC), while there was no significant effect on erythroid and multipotential precursors.

scholarly journals Interleukin-6 enhances growth factor-dependent proliferation of the blast cells of acute myeloblastic leukemia

Blood ◽  
1988 ◽  
Vol 72 (2) ◽  
pp. 823-826
Author(s):  
T Hoang ◽  
A Haman ◽  
O Goncalves ◽  
GG Wong ◽  
SC Clark
Keyword(s):  
Interleukin 6 ◽  
Bone Marrow Cells ◽  
Acute Myeloblastic Leukemia ◽  
Gm Csf ◽  
Normal Bone ◽  
Blast Cells ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor ◽  
Stimulation Of

The effects of recombinant interleukin-6 (IL-6) on the proliferation of blast precursors present in the peripheral blood of patients with acute myeloblastic leukemia (AML) was investigated. IL-6 had little effect by itself; however, it synergized with granulocyte macrophage colony- stimulating factor (GM-CSF) and interleukin-3 (IL-3) in the stimulation of AML blast colony formation. Responsiveness of blast progenitors to IL-6 was heterogeneous. On normal bone marrow cells the same synergy was observed on granulocyte and monocyte precursors (GM-CFC), while there was no significant effect on erythroid and multipotential precursors.

scholarly journals The effects of three recombinant growth factors, IL-3, GM-CSF, and G- CSF, on the blast cells of acute myeloblastic leukemia maintained in short-term suspension culture

Blood ◽  
1987 ◽  
Vol 70 (3) ◽  
pp. 657-663 ◽  
Author(s):  
J Miyauchi ◽  
CA Kelleher ◽  
YC Yang ◽  
GG Wong ◽  
SC Clark ◽  
...  
Keyword(s):  
Growth Factors ◽  
Acute Myeloblastic Leukemia ◽  
Colony Stimulating Factor ◽  
Short Term ◽  
Gm Csf ◽  
Bladder Cell ◽  
Blast Cells ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract The blast stem cells of acute myeloblastic leukemia (AML) respond in cell culture to growth factors by both self-renewal and terminal divisions. Both of these functions have been shown to be stimulated by the recombinant growth factors granulocyte-macrophage colony- stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF). In this paper, recombinant gibbon interleukin-3 (IL-3), homologous to human IL-3, was tested on blast cells and compared with the effects of GM-CSF, G-CSF, and medium conditioned by the bladder cell line 5637 (5637-CM). We found that IL-3 was an effective stimulator of blast renewal and terminal divisions. However, great patient-to-patient variation was found. A graphic method of presenting complex comparisons between growth factors is also included.

scholarly journals The effects of three recombinant growth factors, IL-3, GM-CSF, and G- CSF, on the blast cells of acute myeloblastic leukemia maintained in short-term suspension culture

Blood ◽  
1987 ◽  
Vol 70 (3) ◽  
pp. 657-663 ◽  
Author(s):  
J Miyauchi ◽  
CA Kelleher ◽  
YC Yang ◽  
GG Wong ◽  
SC Clark ◽  
...  
Keyword(s):  
Growth Factors ◽  
Acute Myeloblastic Leukemia ◽  
Colony Stimulating Factor ◽  
Short Term ◽  
Gm Csf ◽  
Bladder Cell ◽  
Blast Cells ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

The blast stem cells of acute myeloblastic leukemia (AML) respond in cell culture to growth factors by both self-renewal and terminal divisions. Both of these functions have been shown to be stimulated by the recombinant growth factors granulocyte-macrophage colony- stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF). In this paper, recombinant gibbon interleukin-3 (IL-3), homologous to human IL-3, was tested on blast cells and compared with the effects of GM-CSF, G-CSF, and medium conditioned by the bladder cell line 5637 (5637-CM). We found that IL-3 was an effective stimulator of blast renewal and terminal divisions. However, great patient-to-patient variation was found. A graphic method of presenting complex comparisons between growth factors is also included.

scholarly journals Construction of Recombinant Human GM-CSF and GM-CSF-ApoA-I Fusion Protein and Evaluation of Their Biological Activity

2021 ◽  
Vol 14 (5) ◽  
pp. 459
Author(s):  
Mariya Pykhtina ◽  
Svetlana Miroshnichenko ◽  
Vladimir Romanov ◽  
Antonina Grazhdantseva ◽  
Galina Kochneva ◽  
...  
Keyword(s):  
Bone Marrow Cells ◽  
E Coli ◽  
Gm Csf ◽  
Human Apolipoprotein ◽  
Proliferative Effect ◽  
Erythroleukemia Cells ◽  
Blast Cells ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

In this study, two strains of the yeast P. pastoris were constructed, one of which produced authentic recombinant human granulocyte-macrophage colony-stimulating factor (ryGM-CSF), and the other was a chimera consisting of ryGM-CSF genetically fused with mature human apolipoprotein A-I (ApoA-I) (ryGM-CSF-ApoA-I). Both forms of the cytokine were secreted into the culture medium. The proteins’ yield during cultivation in flasks was 100 and 60 mg/L for ryGM-CSF and ryGM-CSF-ApoA-I, respectively. Both forms of recombinant GM-CSF stimulated the proliferation of human TF-1 erythroleukemia cells; however, the amount of chimera required was 10-fold that of authentic GM-CSF to induce a similar proliferative effect. RyGM-CSF exhibited a 2-fold proliferative effect on BFU-E (burst-forming units—erythroid) at a concentration 1.7 fold less than non-glycosylated E. coli-derived GM-CSF. The chimera together with authentic ryGM-CSF increased the number of both erythroid precursors and BMC granulocytes after 48 h of incubation of human bone marrow cells (BMCs). In addition, the chimeric form of ryGM-CSF was more effective at increasing the viability of the total amount of BMCs, decreasing apoptosis compared to the authentic form. ryGM-CSF-ApoA-I normalized the proliferation, maturation, and segmentation of neutrophils within the physiological norm, preserving the pool of blast cells under conditions of impaired granulopoiesis. The chimera form of GM-CSF exhibited the properties of a multilinear growth factor, modulating the activity of GM-CSF and, perhaps, it may be more suitable for the normalization of granulopoiesis.

scholarly journals Effects of recombinant GM-CSF on the blast cells of acute myeloblastic leukemia

Blood ◽  
1986 ◽  
Vol 68 (1) ◽  
pp. 313-316 ◽  
Author(s):  
T Hoang ◽  
N Nara ◽  
G Wong ◽  
S Clark ◽  
MD Minden ◽  
...  
Keyword(s):  
Suspension Culture ◽  
Adherent Cells ◽  
Colony Stimulating Factor ◽  
Response Curves ◽  
Self Renewal ◽  
Gm Csf ◽  
Blast Cells ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

The effects of recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) were compared to those of media conditioned by the continuous bladder carcinoma line, HTB9 (HTB9-CM), using three criteria. First, both GM-CSF and HTB9-CM stimulated blast colony formation in methylcellulose cultures, patient-to-patient variations were seen in the dose-response curves, and GM-CSF was effective, but less so that HTB9-CM. Second, GM-CSF also enhanced growth of blast progenitors in suspension culture, indicating its capacity to support self-renewal. GM-CSF was as effective as HTB9-CM in the production of adherent cells during the growth of blast cells in suspension, a finding that is interpreted to mean that GM-CSF also supports postdeterministic events in blast differentiation. Finally, colonies growing in the presence of GM-CSF were not phenotypically different than those stimulated by HTB9-CM.

scholarly journals Enhanced expression of the granulocyte-macrophage colony stimulating factor gene in acute myelocytic leukemia cells following in vitro blast cell enrichment

Blood ◽  
1988 ◽  
Vol 72 (4) ◽  
pp. 1329-1332 ◽  
Author(s):  
DC Kaufman ◽  
MR Baer ◽  
XZ Gao ◽  
ZQ Wang ◽  
HD Preisler
Keyword(s):  
T Cell ◽  
Leukemic Cells ◽  
Acute Myelocytic Leukemia ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Myelocytic Leukemia ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Expression of the granulocyte-macrophage colony-stimulating factor (GM- CSF) gene in acute myelocytic leukemia (AML) was assayed by Northern blot analysis. GM-CSF messenger RNA (mRNA) was detected in the freshly obtained mononuclear cells of only one of 48 cases of AML, in contrast with recent reports that GM-CSF mRNA might be detected in half of the cases of AML when RNA is prepared from T-cell- and monocyte-depleted leukemic cells. We did find, however, that expression of the GM-CSF gene was detectable in five of ten cases after in vitro T-cell and monocyte depletion steps. Additional studies suggest that expression of GM-CSF in the bone marrow of the one positive case, rather than being autonomous, was under exogenous control, possibly by a paracrine factor secreted by marrow stromal cells. These studies emphasize the potential for altering in vivo patterns of gene expression by in vitro cell manipulation.

scholarly journals Activation of the interleukin-3 gene by chromosome translocation in acute lymphocytic leukemia with eosinophilia [see comments]

Blood ◽  
1990 ◽  
Vol 76 (2) ◽  
pp. 285-289 ◽  
Author(s):  
TC Meeker ◽  
D Hardy ◽  
C Willman ◽  
T Hogan ◽  
J Abrams
Keyword(s):  
Acute Lymphocytic Leukemia ◽  
Chromosome Translocation ◽  
Lymphocytic Leukemia ◽  
Leukemic Cells ◽  
Interleukin 3 ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
B Lineage ◽  
Stimulating Factor

Abstract The t(5;14)(q31;q32) translocation from B-lineage acute lymphocytic leukemia with eosinophilia has been cloned from two leukemia samples. In both cases, this translocation joined the IgH gene and the interleukin-3 (IL-3) gene. In one patient, excess IL-3 mRNA was produced by the leukemic cells. In the second patient, serum IL-3 levels were measured and shown to correlate with disease activity. There was no evidence of excess granulocyte/macrophage colony stimulating factor (GM-CSF) or IL-5 expression. Our data support the formulation that this subtype of leukemia may arise in part because of a chromosome translocation that activates the IL-3 gene, resulting in autocrine and paracrine growth effects.

scholarly journals Characterization of the human burst-forming unit-megakaryocyte

Blood ◽  
1989 ◽  
Vol 74 (1) ◽  
pp. 145-151 ◽  
Author(s):  
RA Briddell ◽  
JE Brandt ◽  
JE Straneva ◽  
EF Srour ◽  
R Hoffman
Keyword(s):  
Colony Formation ◽  
Progenitor Cell ◽  
Recombinant Erythropoietin ◽  
Hematopoietic Growth Factors ◽  
Gm Csf ◽  
Hla Dr ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Stimulating Factor

Abstract Two classes of human marrow megakaryocyte progenitor cells are described. Colony-forming unit-megakaryocyte (CFU-MK)-derived colonies appeared in vitro after 12-day incubation; burst-forming unit- megakaryocyte (BFU-MK)-derived colonies appeared after 21 days. CFU-MK- derived colonies were primarily unifocal and composed of 11.6 +/- 1.2 cells/colony; BFU-MK-derived colonies were composed of 2.3 +/- 0.4 foci and 108.6 +/- 4.4 cells/colony. CFU-MK and BFU-MK were separable by counterflow centrifugal elutriation. CFU-MK colony formation was diminished by exposure to 5-fluorouracil (5-FU); BFU-MK colony formation was unaffected. CFU-MK and BFU-MK were immunologically phenotyped. CFU-MK expressed the human progenitor cell antigen-1 (HPCA- 1, CD34, clone My10) and a major histocompatibility class II locus, HLA- DR, and BFU-MK expressed only detectable amounts of CD34. BFU-MK colony formation was entirely dependent on addition of exogenous hematopoietic growth factors. Recombinant granulocyte macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) possessed such colony- stimulating activity, whereas recombinant erythropoietin (Epo), G-CSF, IL-1 alpha, IL-4, and purified thrombocytopoiesis-stimulating factor did not. These studies indicate the existence of a human megakaryocyte progenitor cell, the BFU-MK, which has unique properties allowing it to be distinguished from the CFU-MK.

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