ASXL1 mutations in myeloid neoplasms: pathogenetic considerations, impact on clinical outcomes and survival

Abstract

Background: ASXL1 gene mutations include nonsense, missense, and frameshift mutations. Although their clinical significance is still debated, they may play an important role in the pathogenesis of several hematologic malignancies.

Methods: Herein, we offer a comprehensive review on ASXL1 mutations, and link them with survival and clinical outcomes in patients with various myeloid neoplasms. Most relevant publications were identified through searching the PubMed/Medline database for articles published from inception to February 2016.

Findings: In acute myeloid leukemia (AML), ASXL1 mutations tend to correlate with older age and male gender, and affect predominantly patients with secondary AML. De novo AML patients with ASXL1 mutations had significantly lower complete remission rates after standard high-dose chemotherapy and shorter survival. In chronic myelomonocytic leukemia and low- or intermediate-risk myelodysplastic syndromes, frameshift and nonsense mutations correlated with shorter survival and a higher risk of leukemic transformation. Overall survival was also shorter in primary myelofibrosis in the presence of ASXL1 mutations.

Conclusions: Further research on the role of ASXL1 mutations and therapeutic implications in neoplastic myeloid disorders is stringently needed. Given the relatively high prevalence of ASXL1 mutations, larger studies involving patients affected by these mutations will be feasible in the near future.

Keywords:

• Acute myeloid neoplasms
• AML
• ASXL1
• ASXL1 mutation
• MDS
• myelodysplastic syndrome
• myeloid neoplasms

Transparency

Declaration of funding

This review was not funded.

Declaration of financial/other relationships

J.A.A. and C.D. have disclosed that they have no significant relationships with or financial interests in any commercial companies related to this study or article.

CMRO peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Acknowledgement

The authors thank Marie-Joëlle Mozziconacci and Daniel Birnbaum from the Institut Paoli-Calmettes, Centre de Recherche en Cancerologie de Marseille, France, for allowing the authors to use the image used in figure 1.