Precision medicine for acute myeloid leukemia

Abstract

The goal of precision medicine is to personalize therapy based on individual patient variation, to correctly select the right treatment, for the right patient, at the right time. Acute myeloid leukemia (AML) is a heterogeneous collection of myeloid malignancies with diverse genetic etiology and the potential for intra-patient clonal evolution over time. We discuss here how the precision medicine paradigm might be applied to the care of AML patients by focusing on the potential roles of targeting therapy by patient-specific somatic mutations and aberrant pathways, ex-vivo drug sensitivity and resistance testing, high sensitivity measurements of residual disease burden and biology along with potential clinical trial and regulatory constraints.

Modelling the Effects of MCM7 Variants, Somatic Mutations, and Clinical Features on Acute Myeloid Leukemia Susceptibility and Prognosis

“…Furthermore, for the AML group, considered representative for our region, we found an association between the somatic mutations and high WBC count, high blast percentage, and high LDH level, as previously reported [12,33]. Therefore, patients with a high level of LDH, blast percentage, and WBC count need not only a faster investigation for FLT3 and NPM1 mutations, but also to be correctly classified and receive the benefit of personalized treatment (the goal of precision medicine) in the shortest time [34][35][36][37][38].…”

Aurora A and NF-κB Survival Pathway Drive Chemoresistance in Acute Myeloid Leukemia via the TRAF-Interacting Protein TIFA

“…Although significant progress has been achieved, current treatments for AML may only offer limited survival benefits rather than provide fully satisfactory responses, presumably due to chemoresistance and disease relapse (1,2). To reduce recurrence rate and promote therapeutic efficacy, it is highly urgent to identify new targets (3,4).…”

Acute myeloid leukemia: advancing clinical trials and promising therapeutics

“…There are three predominant ways by which molecular mutations impact therapy in leukemia(57). Firstly, mutated or aberrantly expressed genes are potential targets for small-molecule inhibitors or monoclonal antibodies.…”

“…Advances in the molecular characterization of pathogenic mechanisms of leukemiogenesis have resulted in the identification of mutations in a number of genes that regulate somatic and epigenetic pathways with prognostic and therapeutic implications (1, 6–12). A number of clinically active agents targeting the aberrant protein products of these mutated genes are currently in clinical trials(13).…”