Responses of hemopoietic precursors to 13-cis retinoic acid and 1,25
dihydroxyvitamin D3 in the myelodysplastic syndromes
G Swanson, V Picozzi, R Morgan, F Hecht and P Greenberg
To determine the effects of the "maturation-inducing" agents 13-cis
retinoic acid and 1,25 dihydroxyvitamin D3 on marrow cells from normal
individuals and patients with myelodysplastic syndromes (MDS), we assessed
marrow hemopoietic clonogenicity and differentiation response patterns to
these agents. These vitamins caused increased proliferation in vitro of
normal clonogenic marrow myeloid precursor cells (CFU-GM), decreased
erythroid precursors (BFU-E), and no change in multipotent stem cells
(CFU-GEMM). Marrow hemopoietic colony-forming cell incidence was generally
subnormal in the 22 MDS patients evaluated. In vitro exposure to both
agents caused various patterns of alteration of MDS hemopoietic colony and
cluster formation, with similar but more pronounced effects evoked by
retinoic acid. In the vast majority of MDS patients, enhanced marrow clonal
granulocyte-monocyte differentiation and decreased BFU-E growth were noted
after in vitro exposure to these vitamins. Correlation of biological
effects was demonstrated between in vivo changes of peripheral neutrophil
counts and in vitro responses of myeloid precursors for ten MDS patients
treated with an eight-week therapeutic course of retinoic acid. Cytogenetic
analyses indicated persisting aneuploidy or coexisting normal and aneuploid
karyotypes in the cultured MDS myeloid cells and (with one exception) in
native marrow cells from the treated patients. The varying responses of the
MDS cells may monitor differing proportions of normal versus leukemic
marrow cells susceptible to proliferative and differentiative expression on
exposure to these agents.
Volume 67,
Issue 4,
pp. 1154-1161,
04/01/1986
Copyright © 1986 by The American Society of Hematology
