All-rrans-retinoic acid (RA) induces differentiation of malignant cells and influences normal development (1-3). Actions of RA are thought to be mediated by specific cytoplasmic or nuclear receptors. The RA nuclear receptor alpha (RAR-a) appears to be the predominant RA-binding receptor expressed in various hematopoietic cells (4-8). Retroviral vector-mediated transduction of RAR-a into an RA-resistant subclone of the human leukemia cell line HL-60 can restore sensitivity to RA (9), indicating a direct role for RAR-a in this differentiation program. Clinical trials of all-/ra «s-RA have shown that this agent induces complete remission in a high proportion of patients with acute promyelocytic leukemia (70, 7/). Since RAR-a maps to chromosome 17 in the region of the characteristic cytogenetic abnormality of acute promyelocytic leukemia, translocation t (15; 17)(q22; ql2)(12-14), we studied RAR-a expression in the course of our clinical studies of RA in acute promyelocytic leukemia (75).

In this communication, we report the following: 1) leukemic cells from patients with acute promyelocytic leukemia express aberrant messenger RNA (mRNA) transcripts for RAR-a; 2) expression of both normal and aberrant RAR-a transcripts increases after 1 week of RA treatment; and 3) augmentation of the transcript, as well as the clinical response, occurs at low plasma concentrations.