Predictive modelling of acute Promyelocytic leukaemia resistance to retinoic acid therapy.

Acute Promyelocytic Leukaemia (APL) arises from an aberrant chromosomal translocation involving the Retinoic Acid Receptor Alpha (RARA) gene, predominantly with the Promyelocytic Leukaemia (PML) or Promyelocytic Leukaemia Zinc Finger (PLZF) genes. The resulting oncoproteins block the haematopoietic differentiation program promoting aberrant proliferative promyelocytes. Retinoic Acid (RA) therapy is successful in most of the PML::RARA patients, while PLZF::RARA patients frequently become resistant and relapse.

Noncanonical EZH2 drives retinoic acid resistance of variant acute promyelocytic leukemias.

Cancer cell heterogeneity is a major driver of therapy resistance. To characterize resistant cells and their vulnerabilities, we studied the PLZF-RARA variant of acute promyelocytic leukemia, resistant to retinoic acid (RA), using single-cell multiomics. We uncovered transcriptional and chromatin heterogeneity in leukemia cells.

Smart bracelet to assess physical activity after cardiac surgery: A prospective study.

Objectives: Little is known about the physical activity of patients after cardiac surgery. This study was designed to assess this activity using a connected bracelet.

Methods: In this prospective, monocentric study, patients scheduled for cardiac surgery were offered to wear an electronic bracelet.

PLZF limits enhancer activity during hematopoietic progenitor aging.

PLZF (promyelocytic leukemia zinc finger) is a transcription factor acting as a global regulator of hematopoietic commitment. PLZF displays an epigenetic specificity by recruiting chromatin-modifying factors but little is known about its role in remodeling chromatin of cells committed toward a given specific hematopoietic lineage. In murine myeloid progenitors, we decipher a new role for PLZF in restraining active genes and enhancers by targeting acetylated lysine 27 of Histone H3 (H3K27ac).

Regulation of the positive transcriptional effect of PLZF through a non-canonical EZH2 activity.

The transcription factor PLZF (promyelocytic leukemia zinc finger protein) acts as an epigenetic regulator balancing self-renewal and differentiation of hematopoietic cells through binding to various chromatin-modifying factors. First described as a transcriptional repressor, PLZF is also associated with active transcription, although the molecular bases underlying the differences are unknown. Here, we reveal that in a hematopoietic cell line, PLZF is predominantly associated with transcribed genes.