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19 - Pharmacogenetic studies in pediatric acute myeloid leukemia

from Part IV - Next-generation sequencing technology and pharmaco-genomics

Published online by Cambridge University Press:  18 December 2015

By
Neha S. Bhise ,
Lata Chauhan  and
Jatinder Kaur Lamba
Edited by
Krishnarao Appasani
Foreword by
Stephen W. Scherer  and
Peter M. Visscher
Neha S. Bhise
Affiliation:
University of Minnesota
Lata Chauhan
Affiliation:
University of Florida
Jatinder Kaur Lamba
Affiliation:
University of Florida
Krishnarao Appasani
Affiliation:
GeneExpression Systems, Inc., Massachusetts
Stephen W. Scherer
Affiliation:
University of Toronto
Peter M. Visscher
Affiliation:
University of Queensland
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Summary

Introduction

Acute myeloid leukemia (AML) is a clonal disorder characterized by appearance of immature, abnormal myeloid cells in bone marrow and other organs. AML accounts for around 15–20% of childhood leukemias. AML is a very heterogeneous disease with various subtypes classified based on the morphology, immunophenotype, and cytogenetics. In spite of advances in recent years, the 5-year survival rates for AML are ~68% for children younger than 15 years and ~57% for children between 15 and 19 years. The utilization of multiple clinical, cytogenetic, and other molecular features that are associated with response has helped in the identification of a patient being more or less likely to respond. Additionally, minimal residual disease (MRD after induction 1) has been identified as a powerful predictor of poor outcome. The nucleoside analog cytarabine (ara-C) has been the mainstay of AML chemotherapy for more than 40 years. However, extensive inter-patient variation in treatment response, development of resistance, and inadequate response to first-line therapy remain the major hurdles to effective chemotherapy. Patients within standard and high-risk categories often experience induction failure and have early relapse, warranting the need for better diagnostic and therapeutic strategies. One of the critical components contributing to the efficacy of the chemotherapeutic agents is variability in the expression and/or activity of genes involved in drug pharmacokinetics and pharmacodynamics. This chapter summarizes the recent advances in pediatric AML pharmacogenomics.

Pediatric acute myeloid leukemia

Leukemia is the most common cancer among children, with acute lymphocytic leukemia being the most common and AML being the second most common leukemia in children. Approximately 800 new cases of childhood AML are diagnosed in the US annually (Meshinchi and Arceci, 2007; Pui et al., 2011). AML is a clonal disorder originating from a hematopoietic stem cell or lineage-specific progenitor cells (Jordan, 2007; Lane et al., 2009). The malignant transformation of the stem or progenitor cells results in the accumulation of immature myeloid cells in the bone marrow and other organs. Prognostic factors help in strategizing the treatment regimens for patients with less or more likelihood of response. As indicated before, AML is a very heterogeneous disease with several subtypes that differ from one another in morphology, immunophenotye, and cytogenetics.

Type
Chapter
Information
Genome-Wide Association Studies
From Polymorphism to Personalized Medicine
 , pp. 281 - 296
Publisher: Cambridge University Press
Print publication year: 2016

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