Effects of interleukin 3, interleukin 7, and B-cell growth factor on proliferation and drug resistance in vitro in childhood acute lymphoblastic leukemia.
Growth factors have been reported to enhance the cytotoxicity of anticancer agents. In our study we investigated the capacities of interleukin 3 (IL-3), interleukin 7 (IL-7), low-molecular-weight B-cell growth factor (lmw-BCGF), and IL-3 + 7 to induce proliferation and to modulate the drug resistance of childhood acute lymphoblastic leukemia (ALL) cells. Proliferation was assessed with the methyl-thiazole-tetrazolium (MTT) assay and other parameters. Cellular resistance to cytarabine, thioguanine, and prednisolone was measured using the MTT assay. In 19 samples containing >90% leukemic cells the proliferative response and the modulation of drug resistance was markedly heterogeneous between patient samples and between growth factors. All growth factors were able to stimulate proliferation significantly after 5 days of culture. lmw-BCGF was the most potent growth factor in this respect. Cytotoxicity of cytarabine and thioguanine was significantly increased by IL-7, that of thioguanine by IL-3 as well. IL-7 enhanced the cytotoxicity of thioguanine significantly more than IL-3 and lmw-BCGF and that of cytarabine more than IL-3. Cytotoxicity of prednisolone was not significantly influenced by any growth factor. In individual cases, growth factors reduced the cytotoxicity of the drugs. IL-3 + 7 did not add activity to the most potent single growth factor in both proliferation and drug resistance measurements. This study shows that IL-3, IL-7, and lmw-BCGF generally induce and occasionally inhibit proliferation of ALL cells. Furthermore, they may either increase or decrease cytotoxicity of anticancer drugs. This heterogeneous response to growth factors concerning induction of proliferation and modulation of drug resistance should be taken into account in their clinical use.
Duyn
A E
AE
Department of Pediatrics, University Hospital Vrije Universiteit, Amsterdam, The Netherlands.
Kaspers
G J
GJ
Pieters
R
R
Van Zantwijk
C H
CH
Broekema
G J
GJ
Hählen
K
K
Veerman
A J
AJ
D002452:Cell Count; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D003561:Cytarabine / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology*; D015851:Interleukin-7 / Q000494:pharmacology*; D008222:Lymphokines / Q000494:pharmacology*; D008940:Mitotic Index / Q000187:drug effects; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000473:pathology*; D011239:Prednisolone / Q000494:pharmacology; D013866:Thioguanine / Q000494:pharmacology
D007377:Interleukin-3; D015851:Interleukin-7; D008222:Lymphokines; C058162:low molecular weight-B cell growth factor; D003561:Cytarabine; D011239:Prednisolone; D013866:Thioguanine