Suppression of in vitro maintenance of non-promyelocytic myeloid leukemia clonogenic cells by all-trans retinoic acid: modulating effects of dihydroxylated vitamin D3, alpha interferon and 'stem cell factor'.

In a liquid culture system, all-trans retinoic acid (ATRA), alone and in combination with dihydroxylated vitamin D3 (D3) or alpha interferon (alphaIFN) at concentrations achievable in vivo, could significantly suppress the maintenance of non-promyelocytic myeloid leukemia clonogenic cells (CFU-L) in 9/20, 9/18 and 7/11 cases, respectively. That suppression was counteracted only slightly by the addition of 'stem cell factor', a cytokine which promotes CFU-L expansion in vitro. Differentiated cells slightly increased in 5/17 cases only, suggesting the prevalence of anti-proliferative rather than differentiating mechanisms. The present results extend our previous ones and suggest the possible therapeutical value of ATRA+D3 or alphaIFN, even in cases of non-promyelocytic myeloid leukemia.