Related Experiment Video
Updated: Aug 6, 2026

Pooled shRNA Library Screening to Identify Factors that Modulate a Drug Resistance Phenotype
Published on: June 17, 2022
Pharmacogenetics of alkylator-associated acute myeloid leukemia
Eric Knoche1, Howard L McLeod, Timothy A Graubert
1Washington University School of Medicine, Division of Oncology, Stem Cell Biology Section, Campus Box 8007, 660 South Euclid Avenue, St Louis, MO 63110, USA.
Abstract:
Therapy-related acute myeloid leukemia (t-AML) is a lethal late complication of alkylator chemotherapy. The genetic basis of susceptibility to t-AML is poorly understood. Both t-AML and de novo AML are complex genetic diseases, requiring cooperating mutations in interacting pathways for disease initiation and progression. Germline variants of these 'leukemia pathway' genes may cooperate with somatic mutations to induce both de novo and therapy-related AML. Several cancer susceptibility syndromes have been identified that cause an inherited predisposition to de novo and t-AML. The genes responsible for these syndromes are also somatically mutated in sporadic AML. We reason that germline polymorphism in any gene somatically mutated in AML could contribute to t-AML risk in the general population. Identification of these susceptibility alleles should help clinicians develop tailored therapies that reduce the relative risk of t-AML.
Related Concept Videos
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase
Pharmacogenetics of Drug Metabolism: Overview
Pharmacogenomics: Identification of New Drug Targets
Pharmacogenetics of Phase I Enzymes: Cytochrome P450 Isozymes
