الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 187 |  |  |
| | | from | 187 | | |
Abstract
Lympho-hematopoiesis is under the control of hormones that govern the balanced production of differentiated blood cells and regulate the adapted needs of the maturing cell compartments. Several. of these hormones are growth factors and have been obtained in pure form by ~,molecular cloning so that their function can now be examined. In acute leukemia the gulationof hematopoiesis is heavily disturbed as the disease is characterized by the restricted abilities of the precursors to mature to functional end cells. It has not been established at which point these malignant progenitors are transformed to become defective in their response to growth factor stimulation. In this thesis, we present studies that focused on elucidating the role of various human growth factors on human AML growth by character- izing the receptor system of various Us on surface of leukemic blasts ias well as normal hematopoietic cells, and def ining factors that ~modulate the expression of these receptors. We started by comparing the abilities of acute myeloid leukemia (AML) cells, normal monocytes and granulocytes to bind GM-CSF and IL-3 (Chapter III). It was noted that the control of growth and differen- tiation of hematopoietic cells by GM-CSF and IL-3 is closely inter-related (326,58p201). Binding experiments using radiolabeled HGFs revealed that AML blasts (from 8 cases), as well as normal monocytes o xpress membrane structures and that can bind GM-CSF and IL-3 both 60 pmol/L). Chemical crosslinking provided additional evidence for the existence of a common GM-CSF/IL-3 receptor complex as.both GFs bind to proteins with molecular weight values of 130, 105, and 75 MIn addition to this common GM-CSF/IL-3 binding site, three selective GM-CSF or IL-3 binding sites are distin- guished:Yow affinity GM-CSF receptor with no affinity for IL-3 (AML galls and monocytes), a high affinity IL-3 receptor that does not bind GM-CSF (monocytes and some cases of AML) and a receptor with inter- Aediate affinity for GM-CSF that does not bind IL-3 (neutrophils).