PICALM

Overview

PICALM (Phosphatidylinositol Binding Clathrin Assembly Protein) encodes a clathrin assembly protein involved in endocytosis and intracellular trafficking. In hematologic malignancies, PICALM is notable as a fusion partner in the recurrent PICALM–MLLT10 (CALM–AF10) translocation, which is associated with AML and T-ALL. This in-frame fusion disrupts normal hematopoietic differentiation and promotes leukemogenesis.

Alterations observed in the corpus

  • Involved in recurrent in-frame PICALM–MLLT10 fusion detected by RNA-seq in AML; associated with the favorable-risk fusion landscape PMID:23634996

Cancer types (linked)

  • AML: The PICALM–MLLT10 fusion is one of several recurrent in-frame fusions identified by RNA-seq in the TCGA 200-case AML cohort, alongside other favorable-risk translocations PMID:23634996

Co-occurrence and mutual exclusivity

  • PICALM–MLLT10 fusion belongs to the favorable-risk transcription-factor fusion category, which is mutually exclusive with NPM1 mutations and DNMT3A mutations in AML PMID:23634996

Therapeutic relevance

  • Favorable-risk fusions including PICALM–MLLT10 may guide treatment de-escalation strategies; no specific targeted therapies for this fusion are described in the corpus.

Open questions

  • Whether the PICALM–MLLT10 fusion in AML carries the same favorable prognosis as PML–RARA or RUNX1–RUNX1T1 fusions remains to be established in outcome-annotated analyses.

Sources

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