Use of hematopoietic growth factors in the treatment of acute myelogenous leukemia

1997 ◽  
Vol 4 (3) ◽  
pp. 191-195 ◽  
Author(s):  
Arnold Ganser ◽  
Gerhard Heil
Keyword(s):  
Growth Factors ◽  
Acute Myelogenous Leukemia ◽  
Myelogenous Leukemia ◽  
Hematopoietic Growth Factors ◽  
Acute Myelogenous

scholarly journals Blasts from patients with acute myelogenous leukemia express functional receptors for stem cell factor

Blood ◽  
1992 ◽  
Vol 80 (1) ◽  
pp. 60-67
Author(s):  
VC Broudy ◽  
FO Smith ◽  
N Lin ◽  
KM Zsebo ◽  
J Egrie ◽  
...  
Keyword(s):  
Stem Cell ◽  
Growth Factors ◽  
Acute Myelogenous Leukemia ◽  
Stem Cell Factor ◽  
Mononuclear Cells ◽  
Colony Growth ◽  
Receptor Expression ◽  
Myelogenous Leukemia ◽  
Gm Csf ◽  
Acute Myelogenous

Stem cell factor (SCF) acts in concert with lineage-specific growth factors to stimulate the growth of hematopoietic colonies. To determine if neoplastic human hematopoietic cells would also respond to SCF, we cultured marrow mononuclear cells from 20 patients with newly diagnosed acute myelogenous leukemia (AML) and two normal donors with SCF, interleukin 3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), or combinations of growth factors in semisolid medium, and assessed colony growth. SCF receptors (c-kit receptors) were quantitated by equilibrium binding studies with 125I-SCF, and binding parameters were estimated using the ligand program. The cellular distribution of c-kit receptors was determined by autoradiography. Our results show that SCF alone or in combination with IL-3 or GM-CSF increased both the number and size of colonies in 10 of the patients. Receptors for SCF were identified on the blasts from all 20 AML patients. The number of receptors ranged from 600 to 29,000 per cell. In the majority of patients, both high- and low-affinity binding sites were identified. Neither the number of receptors per cell nor the finding of one or two classes of receptors correlated with growth response to SCF. Autoradiographic analysis of 125I-SCF binding to normal marrow mononuclear cells revealed grains associated with blasts and megakaryocytes. Grain counts on blasts from 10 AML patients and on normal marrow blasts suggested that high-affinity c-kit receptor expression on AML blasts is lower than or similar to that of normal blasts. These results identify c-kit receptors on human AML blasts, and indicate that SCF acts synergistically with IL-3 or GM-CSF to stimulate colony growth from the marrow cells of a portion of patients with AML.

scholarly journals Blasts from patients with acute myelogenous leukemia express functional receptors for stem cell factor

Blood ◽  
1992 ◽  
Vol 80 (1) ◽  
pp. 60-67 ◽  
Author(s):  
VC Broudy ◽  
FO Smith ◽  
N Lin ◽  
KM Zsebo ◽  
J Egrie ◽  
...  
Keyword(s):  
Stem Cell ◽  
Growth Factors ◽  
Acute Myelogenous Leukemia ◽  
Stem Cell Factor ◽  
Mononuclear Cells ◽  
Colony Growth ◽  
Receptor Expression ◽  
Myelogenous Leukemia ◽  
Gm Csf ◽  
Acute Myelogenous

Abstract Stem cell factor (SCF) acts in concert with lineage-specific growth factors to stimulate the growth of hematopoietic colonies. To determine if neoplastic human hematopoietic cells would also respond to SCF, we cultured marrow mononuclear cells from 20 patients with newly diagnosed acute myelogenous leukemia (AML) and two normal donors with SCF, interleukin 3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), or combinations of growth factors in semisolid medium, and assessed colony growth. SCF receptors (c-kit receptors) were quantitated by equilibrium binding studies with 125I-SCF, and binding parameters were estimated using the ligand program. The cellular distribution of c-kit receptors was determined by autoradiography. Our results show that SCF alone or in combination with IL-3 or GM-CSF increased both the number and size of colonies in 10 of the patients. Receptors for SCF were identified on the blasts from all 20 AML patients. The number of receptors ranged from 600 to 29,000 per cell. In the majority of patients, both high- and low-affinity binding sites were identified. Neither the number of receptors per cell nor the finding of one or two classes of receptors correlated with growth response to SCF. Autoradiographic analysis of 125I-SCF binding to normal marrow mononuclear cells revealed grains associated with blasts and megakaryocytes. Grain counts on blasts from 10 AML patients and on normal marrow blasts suggested that high-affinity c-kit receptor expression on AML blasts is lower than or similar to that of normal blasts. These results identify c-kit receptors on human AML blasts, and indicate that SCF acts synergistically with IL-3 or GM-CSF to stimulate colony growth from the marrow cells of a portion of patients with AML.

scholarly journals Effects of interleukin-4 and interleukin-6 on the proliferation of CD34+ and CD34- blasts from acute myelogenous leukemia

Blood ◽  
1991 ◽  
Vol 78 (1) ◽  
pp. 197-204 ◽  
Author(s):  
K Akashi ◽  
M Harada ◽  
T Shibuya ◽  
T Eto ◽  
Y Takamatsu ◽  
...  
Keyword(s):  
Growth Factors ◽  
Dna Synthesis ◽  
Acute Myelogenous Leukemia ◽  
Colony Formation ◽  
Myelogenous Leukemia ◽  
Interleukin 4 ◽  
Leukemic Blast ◽  
Colony Stimulating Factor ◽  
Acute Myelogenous ◽  
Stimulating Factor

Abstract We studied the effects of interleukin-4 (IL-4) and IL-6 on the growth of leukemic blasts from 40 patients with acute myelogenous leukemia (AML). Patients were selected on the basis of negativity for a series of B-cell antigens including CD10 and CD19. Twenty-one cases were CD34- positive (CD34+) (greater than 15% of blasts) and the remaining 19 were CD34-negative (CD34-) (less than 3% of blasts). IL-4 alone (100 U/ml) could stimulate either DNA synthesis (with greater than 2.0 stimulation index) or leukemic blast colony formation in 24 of 40 AML patients. In the presence of other growth factors, IL-4 showed divergent effects on IL-3-, granulocyte-macrophage colony-stimulating factor-, granulocyte colony-stimulating factor-, or erythropoietin-dependent colony formation. These effects of IL-4 were observed in both CD34+ and CD34- AML cases. IL-6 (100 U/mL) alone could not stimulate DNA synthesis and blast colony formation except for one CD34+ case. On the other hand, IL- 6 showed synergistic effects on IL-3- and IL-4-dependent blast colony formation in 10 of 12 and 7 of 9 CD34+ AML cases, respectively. Among CD34- AML cases, such synergism was seen only in 1 of 12 cases for IL-3- dependent colony formation and in 3 of 7 cases for IL-4-dependent colony formation. The divergent effect of IL-4 and the synergistic effect of IL-6 were also observed in purified CD34+ leukemic blast populations, indicating that these phenomena are not mediated by accessory cells. The present study suggests that IL-4, alone or in combination with other growth factors, has divergent effects on the growth of AML progenitors irrespective of the CD34 expression, and that IL-6 acts synergistically with IL-3 or IL-4 on the growth of leukemic progenitors preferentially in CD34+ AML.

Significance of Marrow Angiogenesis Factors in Patients with Acute Myelogenous Leukemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4424-4424
Author(s):  
Liang-In Lin ◽  
Cheng-Yeh Lee ◽  
Chung-Yi Hu ◽  
Jih-Luh Tang ◽  
Hwei-Fang Tien
Keyword(s):  
Growth Factors ◽  
Survival Time ◽  
Median Survival ◽  
Acute Myelogenous Leukemia ◽  
Median Survival Time ◽  
Myelogenous Leukemia ◽  
Enzyme Linked Immunosorbent Assay ◽  
Kaplan Meier ◽  
Acute Myelogenous ◽  
Endothelial Growth Factor

Abstract Bone marrow (BM) neoangiogenesis plays an important role in the pathogenesis of acute myelogenous leukemia (AML). Paracrine exchange of growth factors among AML blasts, endothelial cells, and other marrow compartments is believed to contribute to the pathogenesis of AML. The vascular endothelial growth factor (VEGF) and the angiopoietin (ANG) family are the two major classes of growth factors associated with angiogenesis. In the present study, BM plasma from 52 AML patients and 20 normal donors were investigated. We measured the marrow concentrations of seven molecules associated with angiogenesis, VEGF, VEGF/PlGF, VEGF-C, VEGF-D, ANG-1, ANG-2, and Tie-2, by using enzyme-linked immunosorbent assay (ELISA). Compared to normal donors, the marrow levels of VEGF/PlGF, ANG-2, and Tie-2 were increased in patients with AML (p<0.005, <0.0001 and <0.0001, respectively). On the contrary, VEGF-C and ANG-1 levels were decreased in patients with AML (p<0.0001 and <0.0005, respectively). Although the values were not completely normalized, sequential study revealed that at complete remission (CR) period, VEGF/PlGF, ANG-2, and Tie-2 levels were decreased (p<0.005, <0.005 and =0.02, respectively), while VEGF-C increased (p=0.04). Kaplan-Meier survival curves showed that the subgroup of patients with lower Tie-2 level (29 ng/ml) had a longer median survival time than those with higher Tie-2 level (18.9 months versus 2.5 months, p<0.005). In addition, subgroups of patients with higher VEGF/PlGF level (1 pg/ml) and VEGF-D level (350 pg/ml) also had a longer median survival time than those with lower levels (20.8 months versus 7.2 months, p=0.03 and 18.9 months versus 3.4 months, p=0.03, respectively). Taken together, there were significant differences in VEGF/PlGF, VEGF-C, ANG-1, ANG-2, and Tie-2 expressions between AML patients and normal donors. Expressions of VEGF/PlGF, VEGF-D, and Tie-2 might be prognostic markers in AML patients.

scholarly journals Effects of interleukin-4 and interleukin-6 on the proliferation of CD34+ and CD34- blasts from acute myelogenous leukemia

Blood ◽  
1991 ◽  
Vol 78 (1) ◽  
pp. 197-204 ◽  
Author(s):  
K Akashi ◽  
M Harada ◽  
T Shibuya ◽  
T Eto ◽  
Y Takamatsu ◽  
...  
Keyword(s):  
Growth Factors ◽  
Dna Synthesis ◽  
Acute Myelogenous Leukemia ◽  
Colony Formation ◽  
Myelogenous Leukemia ◽  
Interleukin 4 ◽  
Leukemic Blast ◽  
Colony Stimulating Factor ◽  
Acute Myelogenous ◽  
Stimulating Factor

We studied the effects of interleukin-4 (IL-4) and IL-6 on the growth of leukemic blasts from 40 patients with acute myelogenous leukemia (AML). Patients were selected on the basis of negativity for a series of B-cell antigens including CD10 and CD19. Twenty-one cases were CD34- positive (CD34+) (greater than 15% of blasts) and the remaining 19 were CD34-negative (CD34-) (less than 3% of blasts). IL-4 alone (100 U/ml) could stimulate either DNA synthesis (with greater than 2.0 stimulation index) or leukemic blast colony formation in 24 of 40 AML patients. In the presence of other growth factors, IL-4 showed divergent effects on IL-3-, granulocyte-macrophage colony-stimulating factor-, granulocyte colony-stimulating factor-, or erythropoietin-dependent colony formation. These effects of IL-4 were observed in both CD34+ and CD34- AML cases. IL-6 (100 U/mL) alone could not stimulate DNA synthesis and blast colony formation except for one CD34+ case. On the other hand, IL- 6 showed synergistic effects on IL-3- and IL-4-dependent blast colony formation in 10 of 12 and 7 of 9 CD34+ AML cases, respectively. Among CD34- AML cases, such synergism was seen only in 1 of 12 cases for IL-3- dependent colony formation and in 3 of 7 cases for IL-4-dependent colony formation. The divergent effect of IL-4 and the synergistic effect of IL-6 were also observed in purified CD34+ leukemic blast populations, indicating that these phenomena are not mediated by accessory cells. The present study suggests that IL-4, alone or in combination with other growth factors, has divergent effects on the growth of AML progenitors irrespective of the CD34 expression, and that IL-6 acts synergistically with IL-3 or IL-4 on the growth of leukemic progenitors preferentially in CD34+ AML.

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