TY - JOUR
T1 - Granulocyte-colony stimulating factor, granulocyte-macrophage colony stimulating factor, PIXY-321, stem cell factor, interleukin-3, and interleukin-7
T2 - Receptor binding and effects on clonogenic proliferation in acute lymphoblastic leukemia
AU - Drach, Doris
AU - Estrov, Zeev
AU - Zhao, Shourong
AU - Drach, Johannes
AU - Cork, Anne
AU - Collins, Dan
AU - Kantarjian, Hagop
AU - Andreeff, Michael
N1 - Funding Information:
Acknowledgements This study was supported in part by grants from the NIH (CA-16672, CA-57639, and CA-55164), ACS (No CH 531). the Clayton Foundation for Research, the Leukemia Research Foundation, and the Hans und Blanka Moser Foundation.
PY - 1994
Y1 - 1994
N2 - Cytokines are frequently used after chemotherapy of leukemias and solid tumors to augment recovery of normal hematopoiesis. While the regulation of normal and leukemic myelopoiesis is well investigated, little is known about effects of cytokines on growth and differentiation of lymphoblastic leukemia. In this study, we investigated the expression of receptors for G-CSF, GM-CSF, SCF, IL-3, and IL-7 on acute lymphoblastic leukemia (ALL) blasts and the effects of these growth factors (GF) on ALL blast colony formation. The binding of fluorescence-tagged cytokines to receptors on ALL blasts was studied by flow-cytometry in 27 cases of ALL (24 precursor B-ALL, 3 T-ALL). Receptor-binding for myeloid-associated GF was observed in the majority of precursor B-ALL (G-CSF = 100% GM-CSF = 65% IL-3 = 83% SCF = 74% but not in T-ALL. Binding of labelled IL-7 was detected in both precursor B- (92% and T-ALL (100% The presence of receptors for SCF in ALL was confirmed by polymerase chain reaction for c-kit mRNA in 19/21 cases tested. Expression of receptors for G-CSF, GM-CSF, IL-3, and SCF was not associated with expression of myeloid antigens, or with specific cytogenetic abnormalities. The effects of these GF on clonogenic cells were tested in the ALL blast colony assay and varied between samples, but all cytokines were able to increase clonogenic growth. The GM-CSF/IL-3 fusion molecule PIXY-321 was most effective in promoting colony growth. In some cases inhibition of colony formation was found. We conclude that ALL blast cells have receptors not only for IL-7, but also for G-CSF, GM-CSF, SCF, and IL-3. ALL precursors can respond to these GF with changes in their clonogenic growth indicating the presence of functional receptors. Results may have implications, for therapeutic approaches combining cytokines and chemotherapy.
AB - Cytokines are frequently used after chemotherapy of leukemias and solid tumors to augment recovery of normal hematopoiesis. While the regulation of normal and leukemic myelopoiesis is well investigated, little is known about effects of cytokines on growth and differentiation of lymphoblastic leukemia. In this study, we investigated the expression of receptors for G-CSF, GM-CSF, SCF, IL-3, and IL-7 on acute lymphoblastic leukemia (ALL) blasts and the effects of these growth factors (GF) on ALL blast colony formation. The binding of fluorescence-tagged cytokines to receptors on ALL blasts was studied by flow-cytometry in 27 cases of ALL (24 precursor B-ALL, 3 T-ALL). Receptor-binding for myeloid-associated GF was observed in the majority of precursor B-ALL (G-CSF = 100% GM-CSF = 65% IL-3 = 83% SCF = 74% but not in T-ALL. Binding of labelled IL-7 was detected in both precursor B- (92% and T-ALL (100% The presence of receptors for SCF in ALL was confirmed by polymerase chain reaction for c-kit mRNA in 19/21 cases tested. Expression of receptors for G-CSF, GM-CSF, IL-3, and SCF was not associated with expression of myeloid antigens, or with specific cytogenetic abnormalities. The effects of these GF on clonogenic cells were tested in the ALL blast colony assay and varied between samples, but all cytokines were able to increase clonogenic growth. The GM-CSF/IL-3 fusion molecule PIXY-321 was most effective in promoting colony growth. In some cases inhibition of colony formation was found. We conclude that ALL blast cells have receptors not only for IL-7, but also for G-CSF, GM-CSF, SCF, and IL-3. ALL precursors can respond to these GF with changes in their clonogenic growth indicating the presence of functional receptors. Results may have implications, for therapeutic approaches combining cytokines and chemotherapy.
KW - ALL
KW - Cytokine receptors
KW - Cytokines
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U2 - 10.3109/10428199409114143
DO - 10.3109/10428199409114143
M3 - Article
C2 - 7535143
AN - SCOPUS:0028600035
SN - 1042-8194
VL - 16
SP - 79
EP - 88
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
IS - 1-2
ER -