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 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 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.