Human growth hormone and insulin-like growth factor-1 enhance the proliferation of human leukemic blasts.
As the number of long-term survivors of childhood leukemia increases, growth retardation has emerged as a significant complication. Treatment of these children with growth hormone (GH) has been suggested and sporadically implemented. We, therefore, studied the effect of human GH (hGH) and its by-product insulin-like growth factor-1 (IGF-1) on the growth of leukemic cells in vitro. Under serum-free conditions hGH and IGF-1 induced a significant dose-dependent proliferative effect on promyelocytic leukemia (HL60) and Burkitt's lymphoma (Daudi) cell lines. Anti-hGH antibodies negated the stimulatory effect of hGH and anti-IGF-1 serum abrogated the growth-promoting effect enhanced by IGF-1. Similar statistically significant stimulatory properties were found when freshly obtained marrow cells from four of five acute lymphoblastic leukemia (ALL) of childhood and four acute myelogenous leukemia (AML) patients were studied in ALL and AML blast-cell clonogenic assays. ALL colonies increased numerically by 72% (P less than .025) and AML colonies by 92% (P less than .01) in the presence of hGH at concentrations of 2.5 x 10(2) and 3.0 x 10(2) ng/mL, respectively. IGF-1 stimulated ALL and AML blast-colony growth at concentrations ranging from 0.05 to 0.5 ng/mL by up to 105% (P less than .025) and 65% (P less than .03), respectively. Our in vitro data suggest that circulating hGH and IGF-1 may promote leukemic blast cell replication in vivo, and the supplemental administration of hGH to leukemia patients in remission must be carefully monitored for early relapse.
Estrov
Z
Z
Efrati Institute for Blood Cell Research and Cytology, Department of Internal Medicine B, Israel.
Meir
R
R
Barak
Y
Y
Zaizov
R
R
Zadik
Z
Z
D001853:Bone Marrow / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D005260:Female; D013006:Growth Hormone / Q000494:pharmacology*; D006801:Humans; D007223:Infant; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism*; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014410:Tumor Stem Cell Assay
D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone