• Curr Med Res Opin · May 2018

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

    • Juliana Alvarez Argote and Constantin A Dasanu.
    • a Medical College of Wisconsin , Hematology Oncology , Milwaukee , WI , USA.
    • Curr Med Res Opin. 2018 May 1; 34 (5): 757-763.

    BackgroundASXL1 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.MethodsHerein, 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.FindingsIn 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.ConclusionsFurther 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.

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