Gene affected:
ASXL1: Additional sex combs like 1 gene (NM_015338.5)

Clinical significance
ASXL1 mutations are a prognostic biomarker that are associated with shorter overall survival time in myeloid disorders (note importance of co-mutation).

Function of gene

ASXL1 acts as an epigenetic regulator*. Although the precise mechanism of action for ASXL1 is not fully understood, is is known that ASXL1 is a chromatin binding protein that forms a scaffold for transcription activators, repressors, and related proteins. The function of ASXL1 is affected by frameshift and nonsense mutations affecting exons 11 and 12; these result in loss of ASXL1 expression which ultimately (via an intermediate pathway involving PRC2-mediated gene repression) they promote myeloid transformation and leukaemogenesis.

NGS panel gene coverage

The panel covers clinically significant mutation sites affecting exons 11 and 12 of ASXL1

Occurrence:and significance

MDS (16% of cases)
When found in refractory anaemia with excess blasts (RAEB) or refractory cytopaenia with multilineage dysplasia (RCMD) ASLX1 mutations have been shown to be associated with adverse outcome.
CMML (45% of cases)
Associated with increased transformation to AML and decreased overall survival
PMF (35% of cases)
Associated with aggressive disease and decreased overall survival
AML (secondary) (30% of cases)
Associated with poorer prognosis
AML (primary) (7-11% of cases)
Significance unclear

Associated genetic changes:

  • ASXL1 mutation is associated with concurrent mutation of RUNX1 and spliceosome mutations.
  • Adverse effect may be worsened by RUNX co-occurrence.
  • Mutation is inversely correlated with FLT3-ITD or NPM1 or 'DMNT3A mutation.


GeneWiki link:
Gene Wiki entry for ASLX1
1. Prognosis and occurence in myeloid disorders
2. Outcome in MDS
3. ASLX1 in AML
4. ASLX1 in AML