PIC-1/SUMO-1-Modified PML-Retinoic Acid Receptor α Mediates Arsenic Trioxide-Induced Apoptosis in Acute Promyelocytic Leukemia

• DOI: 10.1128/mcb.19.7.5170
• Publication Date: 2015-10-26T10:19:28Z
• Authors: Thomas Sternsdorf; Elena Puccetti; Kirsten Jensen; Dieter Hoelzer; Hans Will; Oliver Gerhard Ot...; Martin Ruthardt
• Keywords: Arsenic Trioxide; Promyelocytic leukemia protein; Tretinoin

Fusion proteins involving the retinoic acid receptor α (RARα) and PML or PLZF nuclear protein are genetic markers of acute promyelocytic leukemia (APL). APLs with PML-RARα PLZF-RARα fusion differ only in their response to (RA) treatment: t(15;17) (PML-RARα-positive) APL blasts sensitive RA vitro, patients enter disease remission after treatment, while those t(11;17) (PLZF-RARα-positive) do not. Recently it has been shown that complete can be achieved upon treatment arsenic trioxide (As2O3) PML-RARα-positive APL, even when patient relapsed is resistant. This appears due apoptosis induced by As2O3 poorly defined mechanisms. Here we report (i) As2O3induces cells expressing PML-RARα, not PLZF-RARα, protein; (ii) partially modified covalent linkage a PIC-1/SUMO-1-like prior whereas not; (iii) induces change modification pattern toward highly forms; (iv) redistribution bodies (PML-NBs) accompanied recruitment PIC-1/SUMO-1 into PML-NBs, probably hypermodification both PML-RARα; (v) As2O3-induced independent DNA binding activity located RARα portion (vi) apoptotic process bcl-2 caspase 3 blocked global inhibitor. Taken together, these data provide novel insights mechanisms involved predict will successful.