A functionally active RAR alpha nuclear receptor is expressed in retinoic acid non responsive early myeloblastic cell lines

Although ail-trans retinoic acid (ATRA) can restore the differentiation cap acity of leukemic promyelocytes, early leukemic myeloblasts are conversely not responsive to ATRA induced granulocytic differentiation. To assess whet her this resistance to ATRA is related to an impaired function of the Retin oic Acid Receptor alpha (RAR alpha), we performed an analysis of RAR alpha expression and transactivation activity, in several myeloid leukemic cell l ines, representative of different types of spontaneous acute myeloid leukem ias. Our results indicate that a functionally active RAR alpha nuclear rece ptor is expressed in all the analyzed cell lines, regardless of their diffe rentiation capacity following exposure to ATRA. The observation that ATRA t reatment is able to induce the expression of retinoic acid target genes, in late- but not in early-myetoblastic leukemic cells, raises the possibility that the differentiation block of these cells is achieved through a chroma tin mediated mechanism. Acetylation is apparently not involved in this proc ess, since the histone deacetylase inhibitor trichostatin A, is not able to restore the differentiation capacity of early leukemic myeloblasts. Furthe r investigation is needed to clarify whether myeloid transcription factors, distinct to RAR alpha, play a role in the resistance of these cells to ATR A treatment.