Publication

Rapid expansion of pre-existing non-leukemic hematopoietic clones frequently follows induction therapy for de novo AML.

Blood. 2015 Dec 2. pii: blood-2015-10-677021. [Epub ahead of print]

Abstract

There is interest in using leukemia-gene panels and next-generation sequencing (NGS) 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 is influencing the clonal evolution of a patient's non-leukemic hematopoietic population. Here we report that 5 of 15 patients with genetic clearance of their founding AML clone 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 (MDS) and were detectable at very low frequencies at the time of AML diagnosis. These results suggest that non-leukemic hematopoietic stem and progenitor cells (HSPCs), 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.

Authors

Wong TN, Miller CA, Klco JM, Petti A, Demeter R, Helton NM, Li T, Fulton RS, Heath SE, Mardis ER, Westervelt P, DiPersio JF, Walter MJ, Welch JS, Graubert TA, Wilson RK, Ley TJ, Link DC.