Abstract PL03-02: The AML genome(s)

Abstract

Abstract Acute Myeloid Leukemia (AML) is a clonal disorder of hematopoietic stem/progenitor cells. These cells have been shown to accumulate random mutations as a function of time; however, some of these mutations are non-random and can cause the expansion of the stem cells that contain them, creating a benign ‘preleukemic’ state that has recently been dubbed “Clonal Hematopoiesis of Indeterminate Potential” (CHIP). As these clones expand, they can occasionally acquire additional mutations that create a profound advantage for these cells, yielding an AML “ founding clone”. Founding clones generate subclones that have unique properties that are probably defined by the specific mutations that they contain. These subclones, found in virtually all AML cases, shape the responses of AML patients to therapy, and often contribute to relapse. Clonal heterogeneity is therefore a hallmark of AML at presentation, and approaches to assess risk of relapse must take this into account. Further, approaches to cure this disease will probably require successful targeting of the mutations that initiate the disease, which are the only ones that are found in all the cells within the tumor. Frequently, the initiating mutations that expand the preleukemic clone are persistent when patients are in clinical remission, strongly suggesting that these events are important for relapse. The precise mechanisms by which canonical initiating events predispose to AML are largely unknown, but many of these mutations do cause significant changes in the epigenome that are probably relevant for pathogenesis. Citation Format: Timothy J. Ley. The AML genome(s). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr PL03-02.