Induction of proliferation of acute myeloblastic leukemia (AML) cells with hemopoietic growth factors.
Like their normal counterparts, leukemic blasts have recently been shown to respond to hemopoietic growth factors in both suspension culture and in semisolid media. In the present study, we have evaluated the proliferative response of 35 AML cases to colony-stimulating factors (CSFs) containing conditioned media derived from the human cell lines GCT, 5637, MO and MG U87, and to human recombinant IL-1 (rh-IL1), IL-3 (rhIL-3), GM-CSF (rhGM-CSF) and G-CSF (rhG-CSF). In the great majority of cases, an increase of 3H-thymidine (3H-TdR) uptake was obtained in response to at least one conditioned medium. The labeling index (LI) and the growth fraction (GF), evaluated in a restricted group of cases, were also increased by the growth factors, suggesting that they act by recruiting leukemic cells in cycle from the resting compartment. The ability of blast populations to form colonies was also studied. Conditioned media were found to induce or significantly increase the clonogenic capacity in 20 cases out of 22. The response of leukemic cells to human recombinant CSFs and rhIL-1, used alone or in combination, was also assayed. The results, in agreement with those obtained with conditioned media, show that each leukemic case displays a different pattern of response to CSFs, and that optimal growth conditions must be individually assessed. The possibility of increasing the fraction of cycling cells in AML populations may represent a way to render them more sensitive to cytostatic agents, with a view to new therapeutic strategies.
Lista
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Istituto di Medicina Interna, Università di Torino, Italy.
Brizzi
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Avanzi
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Veglia
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Resegotti
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Pegoraro
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D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002455:Cell Division / Q000187:drug effects; D003114:Colony-Forming Units Assay; D005260:Female; D006133:Growth Substances / Q000494:pharmacology*; D016298:Hematopoietic Cell Growth Factors; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D013936:Thymidine / Q000378:metabolism; D014316:Tritium
D006133:Growth Substances; D016298:Hematopoietic Cell Growth Factors; D014316:Tritium; D013936:Thymidine