EFFECT OF RETINOIC ACID AND INTERFERON-ALPHA ON GRANULOCYTE-MACROPHAGE COLONY-FORMING CELLS IN CHRONIC MYELOID-LEUKEMIA - INCREASED INHIBITION BY ALL-TRANS-RETINOIC AND 13-CIS-RETINOIC ACIDS IN ADVANCED-STAGE DISEASE

Granulocyte-macrophage colony forming units (CFU-GM) from patients wit h advanced stage chronic myelogenous leukemia (CML), i.e. in blastic c risis (BC) or accelerated phase (AP), were inhibited by all-trans-reti noic acid (tRA) approximately 1000-fold more potently than those from chronic phase (CP) CML patients (median IC50 = 10(-9) M tRA for six CM L-AP/BC cases vs > 10(-6) M tRA for seven CML-CP cases). A similar act ivity pattern was observed for the stereoisomer 13-cis-RA (cRA). There was no apparent correlation of CFU-GM retinoid sensitivity with cloni ng efficiency or other colony characteristics. Interferon alpha-2a (IN F alpha) alone strongly inhibited CFU-GM growth in all four CML-AP/BC cases (IC50 less than or equal to 250 IU/ml) and three out of seven CM L-CP cases (IC50 less than or equal to 500 IU/ml), but there was littl e or no interactive effect between various concentrations of tRA and I NF alpha (50 IU/ml) on CFU-GM from either CML-AP/BC or CML-CP cases. T hese results suggest that CML-AP/BC CFU-GM have some intrinsic molecul ar alteration(s) which markedly enhances their responsiveness to tRA a nd cRA, which may be clinically exploitable.