PML

Overview

PML (Promyelocytic Leukemia) encodes a RING-domain nuclear body protein that functions as a tumor suppressor by regulating apoptosis, senescence, DNA damage response, and transcription. In acute promyelocytic leukemia (APL), the PML–RARA fusion (generated by t(15;17)) is the defining oncogenic event and a canonical target for all-trans retinoic acid (ATRA) and arsenic trioxide therapy. PML–RARA is one of the best-characterized therapeutic targets in oncology.

Alterations observed in the corpus

  • PML–RARA fusion categorized as a favorable-risk transcription-factor fusion in AML; mutually exclusive with NPM1 mutations and DNMT3A mutations in the TCGA 200-case AML cohort PMID:23634996
  • PML-RARA fusion from t(15;17) defines 4% (n=60) of AML; class-defining for a favorable-risk subgroup with HR 0.3 (95% CI 0.2–0.4) for overall survival PMID:27276561.
  • PML–RARA is a classic leukemic fusion recovered in LAML ‘fusion-only’ tumors (n=2) and is among the top druggable pan-cancer fusions (16 LAML samples flagged) in the TCGA 33-cancer-type RNA-seq fusion catalog PMID:29617662.

Cancer types (linked)

  • AML (Acute Promyelocytic Leukemia subtype): PML–RARA fusion is the canonical favorable-risk driver in APL; in the TCGA AML cohort, transcription-factor fusions (including PML–RARA) occurred in 18% of cases and defined a distinct molecular subgroup with few cooperating mutations PMID:23634996

Co-occurrence and mutual exclusivity

  • PML–RARA is mutually exclusive with NPM1, DNMT3A, and other transcription-factor fusions (RUNX1–RUNX1T1, MYH11–CBFB) in AML; MLL-fused samples carry the fewest cooperating mutations PMID:23634996

Therapeutic relevance

  • APL driven by PML–RARA is treated with ATRA and arsenic trioxide, representing one of the first successful targeted therapies in oncology; this context is background knowledge for the TCGA AML study PMID:23634996

Open questions

  • The TCGA AML study does not specifically analyze PML–RARA frequency or outcomes; its inclusion as a favorable-risk reference class supports the broader AML classification framework.

Sources

This page was processed by crosslinker on 2026-05-09. - PMID:27276561

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