MilliporeSigma
  • Home
  • Search Results
  • Clearance of PML/RARA-bound promoters suffice to initiate APL differentiation.

Clearance of PML/RARA-bound promoters suffice to initiate APL differentiation.

Blood (2014-09-27)
Adeline Vitaliano-Prunier, Juliane Halftermeyer, Julien Ablain, Aurélien de Reynies, Laurent Peres, Morgane Le Bras, Daniel Metzger, Hugues de Thé
ABSTRACT

PML/RARA, a potent transcriptional inhibitor of nuclear receptor signaling, represses myeloid differentiation genes and drives acute promyelocytic leukemia (APL). Association of the retinoid X receptor-α (RXRA) coreceptor to PML/RARA is required for transformation, with RXRA promoting its efficient DNA binding. APL is exquisitely sensitive to retinoic acid (RA) and arsenic trioxide (arsenic), which both trigger cell differentiation in vivo. Whereas RA elicits transcriptional activation of PML/RARA targets, how arsenic triggers differentiation remains unclear. Here we demonstrate that extinction of PML/RARA triggers terminal differentiation in vivo. Similarly, ablation of retinoid X receptors loosens PML/RARA DNA binding, inducing terminal differentiation of APL cells ex vivo or in vivo. RXRA sumoylation directly contributes to PML/RARA-dependent transformation ex vivo, presumably by enhancing transcriptional repression. Thus, APL differentiation is a default program triggered by clearance of PML/RARA-bound promoters, rather than obligatory active transcriptional activation, explaining how arsenic elicits APL maturation through PML/RARA degradation.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Arsenic(III) oxide, 99.995% trace metals basis
Sigma-Aldrich
Cycloheximide, Biotechnology Performance Certified
Supelco
Arsenic(III) oxide, certified reference material for titrimetry, certified by BAM, >99.5%
Sigma-Aldrich
Cycloheximide, ≥95% (HPLC)
Supelco
Cycloheximide, PESTANAL®, analytical standard
Sigma-Aldrich
Retinoic acid, ≥98% (HPLC), powder
Sigma-Aldrich
Cycloheximide, from microbial, ≥94% (TLC)
Sigma-Aldrich
Arsenic(III) oxide, ReagentPlus®, ≥99.0%
Sigma-Aldrich
Arsenic(III) oxide, ACS reagent (primary standard)
Supelco
Tretinoin, Pharmaceutical Secondary Standard; Certified Reference Material
Tretinoin, European Pharmacopoeia (EP) Reference Standard
USP
Tretinoin, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
4-Hydroxytamoxifen, ≥70% Z isomer (remainder primarily E-isomer)
Sigma-Aldrich
Cycloheximide solution, Ready-Made Solution, microbial, 100 mg/mL in DMSO, Suitable for cell culture
Sigma-Aldrich
Tamoxifen, ≥99%
Supelco
4-Hydroxytamoxifen, (E) and (Z) isomers (50:50), analytical standard
Supelco
Tamoxifen, analytical standard
Supelco
4-Hydroxytamoxifen, analytical standard, (E) and (Z) isomers (50:50)
Millipore
Cycloheximide solution, 0.1%, suitable for microbiology