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 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 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 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 Synergism between recombinant growth factors, GM-CSF and G-CSF, acting on the blast cells of acute myeloblastic leukemia [published erratum appears in Blood 1987 Jul;70(1):339]

Blood ◽  
1987 ◽  
Vol 69 (5) ◽  
pp. 1498-1503 ◽  
Author(s):  
C Kelleher ◽  
J Miyauchi ◽  
G Wong ◽  
S Clark ◽  
MD Minden ◽  
...  
Keyword(s):  
Growth Factors ◽  
Acute Myeloblastic Leukemia ◽  
Normal Bone Marrow ◽  
Culture Methods ◽  
Gm Csf ◽  
The Third ◽  
Normal Bone ◽  
Blast Cells ◽  
Stimulating Factor ◽  
Stimulation Of

Abstract The genes for the hemopoietic growth factors, GM colony-stimulating factor (CSF) and G-CSF have been cloned, and recombinant material is available for both. We tested these recombinant factors for their effects on the blast cells of acute myeloblastic leukemia (AML). Culture methods are available that support both colony formation by AML blasts and the growth of blast stem cells in suspension. Recombinant GM- CSF is active in both culture systems, although to a varying degree. We found that recombinant G-CSF was also effective; however, the two recombinant factors showed striking synergism for the stimulation of blast growth of cells from five of eight AML patients. In these cases, the combination was equivalent to the stimulating activity of supernatants from the continuous cell line 5637. This conditioned medium (HTB9-CM) is considered the standard for blast growth. Blasts from one of the patients grew without added factor. In another instance, recombinant GM-CSF alone was almost as effective as HTB9-CM. In the third case, both recombinant factors were active, but synergism was not observed and their combined effect was not equivalent to that of HTB9-CM. Both GM-CSF and G-CSF were active on normal bone marrow granulopoietic progenitors, but synergism was not observed. We conclude that the marked heterogeneity observed when AML blasts are examined by other criteria is also observed when their response to growth factors is evaluated.

scholarly journals Synergism between recombinant growth factors, GM-CSF and G-CSF, acting on the blast cells of acute myeloblastic leukemia [published erratum appears in Blood 1987 Jul;70(1):339]

Blood ◽  
1987 ◽  
Vol 69 (5) ◽  
pp. 1498-1503 ◽  
Author(s):  
C Kelleher ◽  
J Miyauchi ◽  
G Wong ◽  
S Clark ◽  
MD Minden ◽  
...  
Keyword(s):  
Growth Factors ◽  
Acute Myeloblastic Leukemia ◽  
Normal Bone Marrow ◽  
Culture Methods ◽  
Gm Csf ◽  
The Third ◽  
Normal Bone ◽  
Blast Cells ◽  
Stimulating Factor ◽  
Stimulation Of

The genes for the hemopoietic growth factors, GM colony-stimulating factor (CSF) and G-CSF have been cloned, and recombinant material is available for both. We tested these recombinant factors for their effects on the blast cells of acute myeloblastic leukemia (AML). Culture methods are available that support both colony formation by AML blasts and the growth of blast stem cells in suspension. Recombinant GM- CSF is active in both culture systems, although to a varying degree. We found that recombinant G-CSF was also effective; however, the two recombinant factors showed striking synergism for the stimulation of blast growth of cells from five of eight AML patients. In these cases, the combination was equivalent to the stimulating activity of supernatants from the continuous cell line 5637. This conditioned medium (HTB9-CM) is considered the standard for blast growth. Blasts from one of the patients grew without added factor. In another instance, recombinant GM-CSF alone was almost as effective as HTB9-CM. In the third case, both recombinant factors were active, but synergism was not observed and their combined effect was not equivalent to that of HTB9-CM. Both GM-CSF and G-CSF were active on normal bone marrow granulopoietic progenitors, but synergism was not observed. We conclude that the marked heterogeneity observed when AML blasts are examined by other criteria is also observed when their response to growth factors is evaluated.

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 Stimulation of human myelopoiesis by leukotrienes B4 and C4: interactions with granulocyte-macrophage colony-stimulating factor

Blood ◽  
1993 ◽  
Vol 81 (2) ◽  
pp. 352-356
Author(s):  
L Stenke ◽  
M Mansour ◽  
P Reizenstein ◽  
JA Lindgren
Keyword(s):  
Colony Formation ◽  
Bone Marrow Cells ◽  
Growth Stimulation ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Synthase Inhibitor ◽  
Stimulating Factor ◽  
Stimulation Of

The regulatory role of leukotrienes (LT) on human myelopoiesis was investigated. Mononuclear bone marrow cells from 31 healthy donors were cultivated in the presence of suboptimal concentrations of recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) for 10 days in semisolid agar. The addition of LTC4 or LTB4 to the cultures dose- dependently stimulated myeloid stem cell proliferation. Maximal effects were observed at 10(-8) mol/L, at which LTC4 induced a 91% +/- 23% (mean +/- SEM; P = .004) and LTB4 a 73% +/- 22% (P = .008) increase in colony formation. In contrast, addition of the LTB4 isomer 5(S), 12(S)- diHETE did not affect the growth. LTD4 exerted a weak potentiating effect on progenitor proliferation (17% +/- 7% growth stimulation at 10(-10) mol/L; P = .034), whereas LTE4 was without consistent effect. Furthermore, LTC4-induced stimulation of colony formation was insensitive to the LTD4 antagonist ICI 198615. The dual lipoxygenase and prostaglandin endoperoxide synthase inhibitor CL42A potently suppressed the proliferation of myeloid colonies, a suppression that could be reversed by parallel addition of LTB4 or LTC4. The results suggest that both LTB4 and LTC4 possess strong and specific synergistic stimulatory effects on GM-CSF-induced human myeloid progenitor cell growth.

scholarly journals Stimulation of human myelopoiesis by leukotrienes B4 and C4: interactions with granulocyte-macrophage colony-stimulating factor

Blood ◽  
1993 ◽  
Vol 81 (2) ◽  
pp. 352-356 ◽  
Author(s):  
L Stenke ◽  
M Mansour ◽  
P Reizenstein ◽  
JA Lindgren
Keyword(s):  
Colony Formation ◽  
Bone Marrow Cells ◽  
Growth Stimulation ◽  
Colony Stimulating Factor ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Synthase Inhibitor ◽  
Stimulating Factor ◽  
Stimulation Of

Abstract The regulatory role of leukotrienes (LT) on human myelopoiesis was investigated. Mononuclear bone marrow cells from 31 healthy donors were cultivated in the presence of suboptimal concentrations of recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) for 10 days in semisolid agar. The addition of LTC4 or LTB4 to the cultures dose- dependently stimulated myeloid stem cell proliferation. Maximal effects were observed at 10(-8) mol/L, at which LTC4 induced a 91% +/- 23% (mean +/- SEM; P = .004) and LTB4 a 73% +/- 22% (P = .008) increase in colony formation. In contrast, addition of the LTB4 isomer 5(S), 12(S)- diHETE did not affect the growth. LTD4 exerted a weak potentiating effect on progenitor proliferation (17% +/- 7% growth stimulation at 10(-10) mol/L; P = .034), whereas LTE4 was without consistent effect. Furthermore, LTC4-induced stimulation of colony formation was insensitive to the LTD4 antagonist ICI 198615. The dual lipoxygenase and prostaglandin endoperoxide synthase inhibitor CL42A potently suppressed the proliferation of myeloid colonies, a suppression that could be reversed by parallel addition of LTB4 or LTC4. The results suggest that both LTB4 and LTC4 possess strong and specific synergistic stimulatory effects on GM-CSF-induced human myeloid progenitor cell growth.

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.

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