Rapid expansion of preexisting nonleukemic hematopoietic clones frequently follows induction therapy for de novo AML

Terrence N. Wong, Christopher Miller, Jeffery M. Klco, Allegra Petti, Ryan Demeter, Nichole M. Helton, Tiandao Li, Robert Fulton, Sharon E. Heath, Elaine R. Mardis, Peter Westervelt, John Dipersio, Matthew Walter, John Welch, Timothy A. Graubert, Richard K. Wilson, Timothy Ley, Daniel Link

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

There is interest in using leukemia-gene panels and next-generation sequencing to assess acute myelogenous leukemia (AML) response to induction chemotherapy. Studies have shown that patients with AML in morphologic remission may continue to have clonal hematopoiesis with populations closely related to the founding AML clone and that this confers an increased risk of relapse. However, it remains unknown how induction chemotherapy influences the clonal evolution of a patient's nonleukemic hematopoietic population. Here, we report that 5 of 15 patients with genetic clearance of their foundingAMLclone after induction chemotherapy had a concomitant expansion of a hematopoietic population unrelated to the initial AML. These populations frequently harbored somatic mutations in genes recurrently mutated in AML or myelodysplastic syndromes and were detectable at very low frequencies at the time of AML diagnosis. These results suggest that nonleukemic hematopoietic stem and progenitor cells, harboring specific aging-acquired mutations,may have a competitive fitness advantage after induction chemotherapy, expand, and persist long after the completion of chemotherapy. Although the clinical importance of these "rising" clones remains to be determined, it will be important to distinguish them from leukemia-related populations when assessing for molecular responses to induction chemotherapy.

Original languageEnglish
Pages (from-to)893-897
Number of pages5
JournalBlood
Volume127
Issue number7
DOIs
StatePublished - Feb 18 2016

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