2(2-(dodecyloxy)ethoxy)ethyl-2-pyridioethyl-phosphate and Leukemia--Myeloid--Acute

Studies were made on whether differentiation and proliferation of antitumor drug-resistant leukemia cells could be controlled by specific inducers of terminal differentiation. Leukemia subclones resistant to daunomycin and/or cytosine arabinoside were isolated from differentiation-inducible mouse myeloid leukemia M1-B24 cells by selection with these antitumor drugs. The drug-resistant cells were found to retain their potential for terminal differentiation induced by various inducers, such as a protein inducer in the conditioned medium of mouse L929 cells, dexamethasone, 1 alpha,25-dihydroxyvitamin D3, 2-[2-(dodecyloxy)ethoxy]ethyl 2-pyridinioethyl phosphate, and poly I. Differentiated cells showed morphological changes to mature macrophage-like cells, increase in phagocytic activity, and decrease in proliferative activity. Clonal analysis of M1-B24 cells showed that the cellular responses to the protein inducer of differentiation were not significantly different between drug-resistant clones selected with anti-tumor drugs and control (drug-sensitive) clones randomly isolated without selection. These results suggest that induction of differentiation of leukemic cells with the specific inducers is another approach to control the drug-resistant leukemia.

Topics: Animals; Calcitriol; Cell Differentiation; Cell Division; Cell Line; Cytarabine; Daunorubicin; Dexamethasone; Drug Resistance; Leukemia, Myeloid, Acute; Methylnitronitrosoguanidine; Mice; Organophosphorus Compounds; Poly I; Pyridinium Compounds

Topics: Animals; Antineoplastic Agents; Cell Differentiation; Humans; Leukemia, Experimental; Leukemia, Myeloid, Acute; Lysophospholipids; Mice; Organophosphorus Compounds; Phospholipids; Pyridinium Compounds