When can real-time quantitative RT-PCR effectively define molecular relapse in acute promyelocytic leukemia patients? (Results of the French Belgian Swiss APL Group).

10-20% of APL patients relapse and the challenge remains to early identify these patients to improve survival rate. We report PML-RARalpha transcript detection by RQ-PCR in 260 consecutive APL patients (n = 970 samples). 223 patients with samples of sufficient RNA quality to demonstrate they reached molecular remission were monitored for MRD.

Favourable outcome in an APL patient with PLZF/RARalpha fusion gene: quantitative real-time RT-PCR confirms molecular response.

Rare cases of acute promyelocytic leukemia (APL) are associated with a t(11;17) translocation and a PLZF-RARalpha fusion transcript. Because of molecular specificities of the fusion protein, ATRA efficiency is often reduced in these cases. We present herein the case of an 83-year old patient which has been successfully treated by ATRA and Daunorubicin.

Frequent antibody production against RARalpha in both APL mice and patients.

In an acute promyelocytic leukemia (APL)-transplantable mouse model, we previously reported the presence of antibodies recognizing PML-RARalpha and RARalpha in the sera of ATRA-treated mice. To evaluate this immune response, we determined the prevalence of anti-RARalpha antibodies in a cohort of 48 APL mice, treated by ATRA (n = 24) or by placebo pellets (n = 24), and in a preliminary subset of 9 patients with APL using a specific enzyme-linked immunosorbent assay (ELISA). In APL mice, significantly higher antibody levels were observed at the latest time points (day 48 to 58 levels superior to day 15 to 18 or day 28 to 38 levels).

Cooperative action of 1alpha,25-dihydroxyvitamin D3 and retinoic acid in NB4 acute promyelocytic leukemia cell differentiation is transcriptionally controlled.

All-trans-retinoic acid (RA) and 1alpha,25-dihydroxyvitamin D3 (1,25D3) are involved in the control of hematopoiesis and have been suggested to play a role in cellular differentiation and are as such potent inducers of differentiation of myeloid leukemia cells. In this study, we show that, in promyelocytic NB4 cells, addition of 1,25D3 enhances terminal granulocytic RA-dependent differentiation concomitant with the enhanced activation of the RA transcriptional activity through an RARbeta promoter. By EMSA and ChIP assays, we further demonstrate that, while both VDR and RAR are bound to the RARbeta promoter in NB4 cells, addition of 1,25D3 increases VDR binding to this promoter, while that of RA induces the release of VDR and increases the binding of RAR.