ASXL1 in AML

Pathway ID: SIGNOR-AML-ASXL1

Description: Additional sex combs-like 1 (ASXL1) is a member of the ASXL family and is involved in epigenetic regulation. ASXL mutations in AML are predominantly frameshift and nonsense mutations generating C-terminally truncated proteins, and are associated with a poor prognosis. The N-terminal ASXH domain mediates interaction with a nuclear ubiquitin carboxy-terminal hydrolase, BAP1. BAP1 is an essential component of the “polycomb repressive deubiquinase complex” (PR-DUB), which leads to gene repression. How ASXL1 mutations, mostly heterozygous somatic mutation, induce myeloid transformation is not fully understood. ASXL1 gene may act as a aploinsufficient or dominant negative tumor suppressor, since loss of ASXL1 function (in promoting H3K27me3) contributes to myeloid transformation and ASXL1 is specifically required for the increased expression of p15(INK4B), in response to oncogenic signaling. On the other hand, cancer-associated ASXL1 mutations aberrantly enhance BAP1. This hyperactive mutant ASXL1/BAP1 complex induces upregulation of posterior HOXA genes and IRF8, thus impairing multilineage differentiation of haematopoietic progenitors. (PMID: 30013160; PMID: 26470845)

Curated by: irozzo

15 Seed Entities

Organism:
Name Primary ID
RXRA P19793
HOXA9 P31269
RARA P10276
FLT3 P36888
CCNA1 P78396
Proliferation SIGNOR-PH4
BCORL1 Q5H9F3
CTBP1 Q13363
CDKN2A P42771
Differentiation SIGNOR-PH37
NCOA1 Q15788
AKT SIGNOR-PF24
ASXL1 Q8IXJ9
EZH2 Q15910
PI3K SIGNOR-C156