ABSTRACT
As mentioned above, APL cells are the only leukemic bone marrow ceHs induced by retinoic acid to differentiate morphologically and functionally. In accordance with this, retinoid treatment of AML other than APL has not been a clinical success. However, it should be noted that in most of these studies 13-cis~ retinoic acid was used. A n of 41 children with AML resulted in one complete remission in a with AML subtype M5 and two partial responses (M4 and M7 subtypes) (76). A phase II study of 13-cis-retinoic acid in adult patients with AML gave no responses among 12 assessable patients (77), but Hoffman and Robinson ( 49) found favorable hematological responses in two adult patients (M2 and M4 subtypes, respectively). That 13-ds-retinoic acid is mostly ineffective in the treatment of AML does not rule out other retinoids in the treatment, especially against the background of the optimistic findings by Ue et al. (15) in children with AML, and because chylomicrons loaded with retinyl esters reduce proliferation of leukemic bone marrow cells in vitro not only with M3 cell type but with several other M-subtype cells. Thus, clinical trials with all-trans-retinoic acid and with retinol are needed in AML, both as a and in combination with other such as cytostatics, cytokines, and other differentiation-inducing
The recent discovery of the retinoic receptors, their ligands, and the connection between a disrupted gene for RARa and APL, with differentiation therapy with retinoic acid, has led to increased knowledge about the role of vitamin A in differentiation and growth. There is currently a very active research within this field. Our knowledge about retinoids, growth, and differentiation both in normal development and in cancer will surely increase considerably within the next few years.
