title: Molecular Mutations and Their Cooccurrences in Cytogenetically Normal Acute Myeloid Leukemia.
abstract: Adult acute myeloid leukemia (AML) clinically is a disparate disease that requires intensive treatments ranging from chemotherapy alone to allogeneic hematopoietic cell transplantation (allo-HCT). Historically, cytogenetic analysis has been a useful prognostic tool to classify patients into favorable, intermediate, and unfavorable prognostic risk groups. However, the intermediate-risk group, consisting predominantly of cytogenetically normal AML (CN-AML), itself exhibits diverse clinical outcomes and requires further characterization to allow for more optimal treatment decision-making. The recent advances in clinical genomics have led to the recategorization of CN-AML into favorable or unfavorable subgroups. The relapsing nature of AML is thought to be due to clonal heterogeneity that includes founder or driver mutations present in the leukemic stem cell population. In this article, we summarize the clinical outcomes of relevant molecular mutations and their cooccurrences in CN-AML, includingNPM1,FLT3ITD,DNMT3A,NRAS,TET2,RUNX1,MLLPTD,ASXL1,BCOR,PHF6,CEBPAbiallelic,IDH1,IDH2R140, andIDH2R170, with an emphasis on their relevance to the leukemic stem cell compartment. We have reviewed the available literature and TCGA AML databases (2013) to highlight the potential role of stem cell regulating factor mutations on outcome within newly defined AML molecular subgroups.
authors.affiliation: Hematologic Malignancies and Stem Cell Transplant, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ 08903, USA.
authors.forename: Mengning
authors.initials: M
authors.lastname: Wang
authors.affiliation: Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Chuanwei
authors.initials: C
authors.lastname: Yang
authors.affiliation: College of Computer and Information Science, Southwest University, Chongqing, China.
authors.forename: Le
authors.identifier: 0000-0002-3708-1727
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Hematologic Malignancies and Stem Cell Transplant, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ 08903, USA.
authors.forename: Dale G
authors.identifier: 0000-0001-7627-548X
authors.initials: DG
authors.lastname: Schaar