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Diagnosis and relapse: cytogenetically normal acute myelogenous leukemia without FLT3-ITD or MLL-PTD. (Leukemia, Mar 2017)

W Chien1,11, Q-Y Sun1,11, L-W Ding1,11, A Mayakonda1,11, S Takao1, L Liu1, S L Lim1, K T Tan1, M Garg1, A De Sousa Maria Varela1, J Xiao1, N Jacob1, K Behrens2, C Stocking2, M Lill3,4, V Madan1, N Hattori1, S Gery3,4, S Ogawa5, S Wakita6, T Ikezoe7, L-Y Shih8, T Alpermann9, T Haferlach9, H Yang1 and H P Koeffler1,3,4,10

1 Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore
2 Heinrich Pette Institute, Hamburg, Germany
3 Department of Hematology-Oncology, Cedars-Sinai Medical Center, Los Angeles, CA, USA
4 Department of Medicine, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA
5 Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
6 Department of Internal Medicine, Division of Hematology, Nippon Medical School, Tokyo, Japan
7 Department of Hematology and Respiratory Medicine, Kochi Medical School, Kochi University, Nankoku, Japan
8 Department of Internal Medicine, Division of Hematology-Oncology, Chang Gung Memorial Hospital, Chang Gung University, Taipei, Taiwan
9 MLL Munich Leukemia Laboratory, Munich, Germany
10 National University Cancer Institute, National University Hospital, Singapore

11 These authors contributed equally to this work.

Most (40–50%) acute myelogenous leukemias (AMLs) are cytogenetically normal (CN-AML). Many are of intermediate risk, and the prognosis may be partially based on their gene mutational profiles. Internal tandem duplication (ITD) of FLT3 gene (FLT3-ITD) occurs in about 25–35% of patients with CN-AML and confers an increased risk of relapse and decreased survival.1 Partial tandem duplication (PTD) of MLL gene (MLL-PTD) occurs in about 5–11% of patients with CN-AML and is associated with an inferior duration of complete remission, relapse-free survival and reduced overall survival.2 A recent study has proposed genomic classification of AML based on driver mutations such as NPM1, TP53 and CEBPA, and how these distinct molecular subgroups may provide informed clinical implication.3 However, a systematic interrogation of clinical heterogeneous subcohort of the remaining 55–70% of CN-AML patients without either FLT3-ITD or MLL-PTD still has not been fully addressed. We have used next-generation sequencing technology to interrogate this heterogeneous subcohort to determine the mutational topography at the initial and relapsed stages of disease. Analysis of their single-nucleotide variants and mutational pattern may lead to better risk stratification and refinement of the therapeutic options for CN-AML. In addition, we closely examined the morphologic complete remission samples for preleukemic driver mutations.d how these distinct molecular subgroups may provide informed clinical implication.3 However, a systematic interrogation of clinical heterogeneous subcohort of the remaining 55–70% of CN-AML patients without either FLT3-ITD or MLL-PTD still has not been fully addressed. We have used next-generation sequencing technology to interrogate this heterogeneous subcohort to determine the mutational topography at the initial and relapsed stages of disease. Analysis of their single-nucleotide variants and mutational pattern may lead to better risk stratific and refinement of the therapeutic options for CN-AML. In addition, we closely examined the morphc complete remission samples for preleukemic driver mutations.

PMID: 27881871