RARA (retinoic acid receptor alpha) haploinsufficiency is an invariable consequence of t(15;17)(q22;q21) translocations in acute promyelocytic leukemia (APL). Retinoids and RARA activity have been implicated in hematopoietic self-renewal and neutrophil maturation. We and others therefore predicted that RARA haploinsufficiency would contribute to APL pathogenesis. To test this hypothesis, we cro...

The PLZF/RARA fusion protein generated by the t(11;17)(q23;q21) translocation in acute promyelocytic leukaemia (APL) is believed to act as an oncogenic transcriptional regulator recruiting epigenetic factors to genes important for its transforming potential. However, molecular mechanisms associated with PLZF/RARA-dependent leukaemogenesis still remain unclear.We searched for specific PLZF/RARA ...

Accurate in-vitro component-based diagnosis will allow clinicians to focus their efforts toward complex issues such as disease severity and reactive dose evaluation as well as establishing effective eviction measures. However to achieve this, clinical utility of component-resolved peanut allergy testing must be rigorously evaluated. In this pilot study, we compared performances of 2 component-r...

Peanuts are one of the most relevant foods implicated in IgE-mediated adverse reactions in pediatric population. This study aimed to evaluate the pattern of sensitization towards five peanut allergenic components (rAra h 1, 2, 3, 8 and 9) in a population of Italian children and adolescents with specific IgE (sIgE) to peanut. rAra h 9 was the main allergen implicated in peanut sensitization (58%...

Acute promyelocytic leukemia (APL) is characterized by expression of promyelocytic leukemia (PML)/retinoic acid (RA) receptor A (RARA) protein and all-trans-RA-mediated clinical remissions. RA treatment can confer PML/RARA degradation, overcoming dominant-negative effects of this oncogenic protein. The present study uncovered independent retinoid degradation mechanisms, targeting different doma...

PML-RARA was proposed to initiate acute promyelocytic leukemia (APL) through PML-RARA homodimer-triggered repression. Here, we examined the nature of the PML-RARA protein complex and of its DNA targets in APL cells. Using a selection/amplification approach, we demonstrate that PML-RARA targets consist of two AGGTCA elements in an astonishing variety of orientations and spacings, pointing to hig...

Ectopic repression of retinoic acid (RA) receptor target genes by PML/RARA and PLZF/RARA fusion proteins through aberrant recruitment of nuclear corepressor complexes drives cellular transformation and acute promyelocytic leukemia (APL) development. In the case of PML/RARA, this repression can be reversed through treatment with all-trans RA (ATRA), leading to leukemic remission. However, PLZF/R...

The majority of acute promyelocytic leukemia (APL) cases are characterized by the presence of a promyelocytic leukemia–retinoic acid receptor alpha(RARA) fusion gene. In a small subset, RARA is fused to a different partner, usually involved in regulating cell growth and differentiation. Here, we identified a novel RARA fusion transcript, BCOR-RARA, in a t(X;17)(p11;q12) variant of APL with uniq...

One of the conclusions of our report1 is that PML/RARa itself mediates RA-dependent differentiation and that its degradation by RAis not crucial for the differentiation process to occur. Naoe and Kitamura disagree. In general, we think that there is much direct and indirect evidence to support these conclusions: (1) PML/RARa is an RA-dependent transcriptional activator2,3; (2) PML/RARa mediates...