Somatic Mutations Precede Acute Myeloid Leukemia Years Before Diagnosis

Overview

Journal Nat Med

Specialties General Medicine
Molecular Biology

Date 2018 Jul 11

PMID 29988143

Citations 272

Authors

Pinkal Desai

Nuria Mencia-Trinchant

Oleksandr Savenkov

Michael S Simon

Gloria Cheang

Sangmin Lee

Michael Samuel

Ellen K Ritchie

Monica L Guzman

Karla V Ballman

Gail J Roboz

Duane C Hassane

Affiliations

Soon will be listed here.

Abstract

The pattern of somatic mutations observed at diagnosis of acute myeloid leukemia (AML) has been well-characterized. However, the premalignant mutational landscape of AML and its impact on risk and time to diagnosis is unknown. Here we identified 212 women from the Women's Health Initiative who were healthy at study baseline, but eventually developed AML during follow-up (median time: 9.6 years). Deep sequencing was performed on peripheral blood DNA of these cases and compared to age-matched controls that did not develop AML. We discovered that mutations in IDH1, IDH2, TP53, DNMT3A, TET2 and spliceosome genes significantly increased the odds of developing AML. All subjects with TP53 mutations (n = 21 out of 21 patients) and IDH1 and IDH2 (n = 15 out of 15 patients) mutations eventually developed AML in our study. The presence of detectable mutations years before diagnosis suggests that there is a period of latency that precedes AML during which early detection, monitoring and interventional studies should be considered.

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