Details

Autor(en) / Beteiligte

• Lehmann-Che, Jacqueline
• Bally, Cecile
• de Thé, Hugues

Titel

Resistance to Therapy in Acute Promyelocytic Leukemia

Ist Teil von

• The New England journal of medicine, 2014-09, Vol.371 (12), p.1170-1172

Ort / Verlag

United States: Massachusetts Medical Society

Erscheinungsjahr

2014

Quelle

MEDLINE

Beschreibungen/Notizen

• Resistance to treatment in patients with acute promyelocytic leukemia is rare. The authors describe the development of resistance to arsenic through a mutation in the allele of PML that is not rearranged as the PML-RARA oncogenic driver. To the Editor: Acute promyelocytic leukemia (APL) is driven by an oncogenic chromosomal translocation fusing the promyelocytic leukemia (PML) and retinoic acid receptor alpha (RARA) genes. APL responds to two targeted therapies: all- trans retinoic acid (ATRA) and arsenic trioxide. Arsenic binds to the PML moiety of the PML-RARA fusion, whereas ATRA binds to its RARA portion; each drug initiates biochemically independent degradation pathways. Degradation of RARA (or PML-RARA) follows transcriptional activation by ATRA. Arsenic trioxide initiates degradation of PML (or PML-RARA) by promoting PML aggregation into subnuclear domains implicated in senescence and apoptosis. Several studies in humans and mice . . .