Landscape of Tumor Suppressor Mutations in Acute Myeloid Leukemia

Journal of Clinical Medicine

Jessica Petiti¹  Chiara Calabrese¹  Cristina Panuzzo¹  Elisabetta Signorino¹  Daniela Cilloni¹  MuhammadShahzad Ali¹  Enrico Bracco² 

[1] Department of Clinical and Biological Sciences, University of Turin, 10124 Turin, Italy;Department of Oncology, University of Turin, 10124 Turin, Italy;

关键词: acute myeloid leukemia;    tumor suppressors;    mutations;    overall survival;    relapse;    epigenetic;    dna repair;    cell cycle;   

DOI  :  10.3390/jcm9030802

来源: DOAJ

【 摘 要 】

Acute myeloid leukemia is mainly characterized by a complex and dynamic genomic instability. Next-generation sequencing has significantly improved the ability of diagnostic research to molecularly characterize and stratify patients. This detailed outcome allowed the discovery of new therapeutic targets and predictive biomarkers, which led to develop novel compounds (e.g., IDH 1 and 2 inhibitors), nowadays commonly used for the treatment of adult relapsed or refractory AML. In this review we summarize the most relevant mutations affecting tumor suppressor genes that contribute to the onset and progression of AML pathology. Epigenetic modifications (TET2, IDH1 and IDH2, DNMT3A, ASXL1, WT1, EZH2), DNA repair dysregulation (TP53, NPM1), cell cycle inhibition and deficiency in differentiation (NPM1, CEBPA, TP53 and GATA2) as a consequence of somatic mutations come out as key elements in acute myeloid leukemia and may contribute to relapse and resistance to therapies. Moreover, spliceosomal machinery mutations identified in the last years, even if in a small cohort of acute myeloid leukemia patients, suggested a new opportunity to exploit therapeutically. Targeting these cellular markers will be the main challenge in the near future in an attempt to eradicate leukemia stem cells.

【 授权许可】

Unknown