In vitro drug sensitivity studies of colony-forming units in culture in chronic myelocytic leukemia: lack of specificity between chronic-phase patients and normal donors

• Published in: Cancer research (Chicago, Ill.) Vol. 43; no. 12 Pt 1; p. 6094
• Main Authors: Kirshner, J, Preisler, H D
• Format: Journal Article
• Language: English
• Published: United States 01.12.1983
• Subjects: Antineoplastic Agents - toxicity; Cells, Cultured; Chromosomes, Human, 21-22 and Y; Clone Cells; Drug Evaluation, Preclinical; Hematopoietic Stem Cells - drug effects; Hematopoietic Stem Cells - physiology; Humans; Leukemia, Myeloid - physiopathology; Prognosis; Reference Values
• ISSN: 0008-5472; 1538-7445

Attempts to eliminate Philadelphia chromosome-positive cells during the treatment of chronic-phase chronic myelocytic leukemia (CML) have been largely unsuccessful, probably due to the lack of specificity of drugs which have been used. In an attempt to develop more specific therapy for CML, an assay for colony-forming units in culture was used to test for differences between CML blood and normal marrow progenitor cells. The following drugs, which have activity in acute nonlymphocytic leukemia, were tested over a range of concentrations achievable in vivo: Adriamycin; 1-beta-D-arabinofuranosylcytosine; aclacinomycin; m(4-acridinylamino)-3-methoxyphenyl methansulfamide; methylglyoxalbis(guanylhydrazone), and 5-azacytidine. [3H]Thymidine suicide indices were also determined. Normal marrow colony-forming units in culture tended to be more sensitive to all the drugs which were tested, although not of statistical significance. There was no difference in the suicide index between CML and normal colony-forming units in culture. It is concluded that the drugs which were tested are not likely to selectively kill CML progenitor cells while permitting normal hematopoietic elements to survive.