PMID- 2015403 OWN - NLM STAT- MEDLINE DCOM- 19910521 LR - 20210216 IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 77 IP - 8 DP - 1991 Apr 15 TI - Two-step differentiation of AML-193 leukemic line: terminal maturation is induced by positive interaction of retinoic acid with granulocyte colony-stimulating factor (CSF) and vitamin D3 with monocyte CSF. PG - 1804-12 AB - The human AML-193 cell line requires exogenous granulocyte-monocyte colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3) for growth in liquid or semisolid medium. However, these CSFs do not stimulate the differentiation of the cell line. We show that addition of all-trans retinoic acid (RA) or 1,25 dihydroxyvitamin D3 (D3) induces AML-193 cells to differentiate into the granulocytic or monocytic lineage, respectively. On the other hand, addition of either G- or M-CSF alone exerts virtually no differentiative effect. Terminal granulocytic or monocytic differentiation was observed when AML-193 cells were treated with RA and G-CSF, or D3 and M-CSF, respectively, as evaluated by cell morphology, analysis of surface antigens, and phagocytic functions. These positive interactions indicate that the differentiating activity of G- and M-CSF on leukemic cells may be unmasked by preliminary treatment with RA and D3, respectively, ie, the physiologic inducers override the leukemic differentiation blockade and CFSs exert their differentiative activity on the unblocked leukemic cells. These preliminary observations on a single cell line may pave the way for the designing of clinical protocols combining physiologic inducer(s) and hematopoietic growth factor(s) in the treatment of acute leukemia. FAU - Valtieri, M AU - Valtieri M AD - Department of Hematology-Oncology, Istituto Superiore di Sanita, Rome, Italy. FAU - Boccoli, G AU - Boccoli G FAU - Testa, U AU - Testa U FAU - Barletta, C AU - Barletta C FAU - Peschle, C AU - Peschle C LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (Antibodies, Monoclonal) RN - 0 (Antigens, CD) RN - 0 (Cytokines) RN - 0 (Recombinant Proteins) RN - 5688UTC01R (Tretinoin) RN - 81627-83-0 (Macrophage Colony-Stimulating Factor) RN - 83869-56-1 (Granulocyte-Macrophage Colony-Stimulating Factor) RN - FXC9231JVH (Calcitriol) SB - IM MH - Antibodies, Monoclonal MH - Antigens, CD/analysis MH - Calcitriol/*pharmacology MH - Cell Differentiation/*drug effects MH - Cell Line MH - Clone Cells MH - Cytokines/*pharmacology MH - Drug Interactions MH - Granulocyte-Macrophage Colony-Stimulating Factor/*pharmacology MH - Humans MH - Kinetics MH - Leukemia, Myeloid, Acute MH - Macrophage Colony-Stimulating Factor/*pharmacology MH - Recombinant Proteins/pharmacology MH - Tretinoin/*pharmacology EDAT- 1991/04/15 00:00 MHDA- 1991/04/15 00:01 CRDT- 1991/04/15 00:00 PHST- 1991/04/15 00:00 [pubmed] PHST- 1991/04/15 00:01 [medline] PHST- 1991/04/15 00:00 [entrez] AID - S0006-4971(20)81581-X [pii] PST - ppublish SO - Blood. 1991 Apr 15;77(8):1804-12.