Genetic background influences susceptibility to chemotherapy-induced hematotoxicity.

Document Type

Article

Publication Date

4-2018

JAX Location

Reprint Collection

JAX Source

Pharmacogenomics J 2018 Apr; 18(2):319-330.

Volume

18

Issue

2

First Page

319

Last Page

330

ISSN

1473-1150

PMID

28607509

DOI

https://doi.org/10.1038/tpj.2017.23

Grant

CA034196, GM070683

Abstract

Hematotoxicity is a life-threatening side effect of many chemotherapy regimens. Although clinical factors influence patient responses, genetic factors may also play an important role. We sought to identify genomic loci that influence chemotherapy-induced hematotoxicity by dosing Diversity Outbred mice with one of three chemotherapy drugs; doxorubicin, cyclophosphamide or docetaxel. We observed that each drug had a distinct effect on both the changes in blood cell subpopulations and the underlying genetic architecture of hematotoxicity. For doxorubicin, we mapped the change in cell counts before and after dosing and found that alleles of ATP-binding cassette B1B (Abcb1b) on chromosome 5 influence all cell populations. For cyclophosphamide and docetaxel, we found that each cell population was influenced by distinct loci, none of which overlapped between drugs. These results suggest that susceptibility to chemotherapy-induced hematotoxicity is influenced by different genes for different chemotherapy drugs. Pharmacogenomics J 2018 Apr; 18(2):319-330.

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