Driving Toward Precision Medicine for Acute Leukemias: Are We There Yet?

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Driving Toward Precision Medicine for Acute Leukemias: Are We There Yet?

Pharmacotherapy. 2017 Jun 27;:

Authors: Chung C, Ma H

Abstract
Despite recent progress in the understanding of the molecular basis of acute leukemias, treatment options for these diseases have not shown significant changes over the last few decades. In this review, we present a nonexhaustive key summary of the current cytogenetic and molecular changes associated with acute leukemias in disease prognostication and potential targeted therapies. An emerging paradigm is that many genetic or molecular alterations target similar signal transduction, transcriptional, and epigenetic pathways. Some of these targets may be used as predictive biomarkers for the development of novel targeted therapies, which depart significantly from conventional chemotherapy, the current mainstay for treatment of acute leukemias. Established leukemia-specific predictive biomarkers for precision medicine include those genetic lesions such as BCR-ABL1 for Philadelphia-positive acute lymphoblastic leukemia (ALL) and PML-RARα for acute promyelocytic leukemia. There is evidence that targeted therapy for FLT-ITD gene mutations with small-molecule tyrosine kinase inhibitors (TKIs) can extend its use from relapsed disease to upfront induction therapy. Core-binding factor (CBF)-AML in adults predicts benefit with high-dose cytarabine in the absence of KIT mutation. Although risk-adapted therapy based on genetic abnormalities in acute leukemias has allowed the beginning of personalized treatment and selective use of hematopoietic stem cell transplantation, the prognostic and/or predictive value of many novel mutations of the acute leukemic genome is yet to be elucidated. Many challenges lie ahead in targeted therapies due to overlapping of chromosomal and molecular lesions as well as other limiting factors. Future work should focus on the understanding of pathogenetic changes that lead to leukemogenesis, which may guide the rational design of new targeted therapies and make the drive toward precision medicine for acute leukemias one step closer. This article is protected by copyright. All rights reserved.

PMID: 28654205 [PubMed - as supplied by publisher]

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