Combinations of stem cell factor with other hematopoietic growth factors enhance growth and sensitivity to cytosine arabinoside of blast progenitors in acute myelogenous leukemia.
The blast progenitors in acute myelogenous leukemia grow in response to hematopoietic growth factors (HGFs), and their sensitivity to antileukemic drugs is influenced by HGFs. We report the effects of stem cell factor (SCF) on the growth and sensitivity to 1-beta-D-arabinofuranosylcytosine (Ara-C) of blast progenitors in acute myelogenous leukemia. SCF stimulated both colony formation and self-renewal of blast progenitors and, when used in combination with other HGFs, synergistic enhancement of colony formation was noted in 8 of the 15 patients examined. Cell fractionation studies demonstrated no unique growth dependency on SCF in either CD34+ or CD34- populations. Blast cells of patients that displayed synergistic growth enhancement with SCF displayed the highest Ara-C sensitivity when HGFs were used in combination with SCF. The tritiated thymidine suicide test (20-min exposure) revealed that the proportion of blast progenitors in the S phase of the cell cycle was highest when SCF and another HGF were simultaneously present, although 24-h exposure killed most or all of the blast progenitors. These data indicate that SCF enhances growth and sensitivity to Ara-C of acute myelogenous leukemia blast progenitors in a closely correlated fashion and that the cell cycle changes as well as other mechanisms are involved in the Ara-C sensitivity modulation by SCF.
Inatomi
Y
Y
Clinical Laboratory, National Children's Hospital, Tokyo, Japan.
Toyama
K
K
Clark
S C
SC
Shimizu
K
K
Miyauchi
J
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D002453:Cell Cycle / Q000187:drug effects; D002675:Child, Preschool; D003561:Cytarabine / Q000494:pharmacology*; D005260:Female; D016298:Hematopoietic Cell Growth Factors / Q000494:pharmacology*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D019089:Stem Cell Factor; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D016298:Hematopoietic Cell Growth Factors; D019089:Stem Cell Factor; D003561:Cytarabine