Induction of erythroid differentiation by the anthracycline antitumor antibiotics, aclacinomycin a, musettamycin and marcellomycin

Abstract

The oligosaccharide anthracycline aclacinomycin A is of considerable clinical interest since, in comparison to adriamycin and daunomycin, the compound exhibits reduced cardiac toxicity and is devoid of mutagenicity/carcinogenicity. In addition, induction of differentiation in the human promyelocytic leukemia cell line HL 60 and possibly in one case of human acute myeloblastic leukemia by aclacinomycin A has been observed. Our data indicate (a) that aclacinomycin A and related compounds, such as musettamycin and marcellomycin, are extremely potent inducers of differentiation in mouse (Friend leukemia cells, clone F4-6), rat (rat erythroleukemia, clone D5A1), and human erythroid cell lines (K 562 cell line) and (b) that the relative inductive potency of marcellomycin and musettamycin, in general, is higher than that of aclacinomycin A. This potency difference may be due to the presence of a Cl-hydroxyl group in the aglycone of the marcellomycin and musettamycin molecule. Thus, oligosaccharide anthracyclines are a new class of inducers of erythroid differentiation. The high potency of these compounds, the possibility to study structure-activity relationships relative to their inductive potency and the fact that they induce erythroid differentiation in cells of different species as well as granulocytic differentiation in human cells should facilitate the study of basic mechanisms of hemopoietic differentiation. In addition, the therapeutical significance of these anthracycline effects should be investigated by studying, comparatively, the differentiation-inducing and antitumor effects of these compounds in primary leukemic cell cultures from patients.