Abstract
Recent advances in the field of cancer genome analysis revolutionized the picture we have of acute myeloid leukemia (AML). Pan-genomic studies, using either single nucleotide polymorphism arrays or whole genome/exome next generation sequencing, uncovered alterations in dozens of new genes or pathways, intimately connected with the development of leukemia. From a simple two-hit model in the late nineties, we are now building clonal stories that involve multiple unexpected cellular functions, leading to full-blown AML. In this review, we will address several seminal concepts that result from these new findings. We will describe the genetic landscape of AML, the association and order of events that define multiple sub-entities, both in terms of pathogenesis and in terms of clinical practice. Finally, we will discuss the use of this knowledge in the settings of new strategies for the evaluation of measurable residual diseases (MRD), using clone-specific multiple molecular targets.
Highlights
Recent advances in the field of cancer genome analysis revolutionized the picture we have of acute myeloid leukemia (AML)
It is worth noting that the incidence of TP53 mutations is increased in secondary AML (s-AML), as compared to de novo AML, this partially explains the dismal prognosis of s-AML
The outstanding progresses of sequencing techniques from the last decades led us to a precise view of how each kind of AML occur in children, young and old adults, in patients with germline defects, or in patients predisposed by aging, or by a toxic exposure
Summary
From a clinical ontogeny point of view, three different kinds of acute myeloid leukemia (AML) can be defined as follows: de novo AML, the occurrence of which cannot be linked to a previously-known hematologic disorder, secondary AML (s-AML), which occurs in a context of myelodysplastic syndrome (MDS) or myeloproliferative neoplasms (MPN), and therapy-related AML (t-AML), which develops secondary to cytotoxic and radiation therapies. This clinical classification does not reflect the high heterogeneity of AML, as each clinical category encompasses many different types of diseases with distinct prognosis and molecular features. Behind these categories, underlie complex and variegated genetic interactions and ontogenies that are not properly set-out by the current classifications
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