Evaluation of semiquantitative reverse transcriptase-polymerase chain reaction assay of PML/retinoic acid receptor alpha mRNA and in vitro differentiation assay as prognostic prediction in acute promyelocytic leukemia treated with all-trans retinoic acid.

We studied the quantitative changes in PML/retinoic acid receptor alpha (PML/RAR alpha) fusion mRNA using the reverse transcriptase-polymerase chain reaction (RT-PCR) and the in vitro differentiation of leukemic cells from eight acute promyelocytic leukemia (APL) patients during treatment with all-trans retinoic acid (ATRA). In three patients, the intensity of the chimeric PML/RAR alpha bands decreased rapidly after the start of ATRA therapy. However, these three patients required variable periods of time to obtain complete remission (CR) (24, 29 and 100 days). In the five other patients, the chimeric bands decreased slowly, and the time until CR also varied (22, 28, 30, 39 and 67 days). As for the in vitro assay, leukemic cells from the three patients who achieved CR in a short period of time (22, 28 and 30 days) showed marked differentiation in response to 1 mumol/L ATRA, and leukemic cells from the four patients with slow or delayed clinical responses to ATRA did not show morphological differentiation in vitro. These findings suggest that the clinical response of APL patients to ATRA is predicted from the results of the in vitro differentiation assay, but not by RT-PCR analysis of the PML/RAR alpha fusion mRNA.