Genetic background influences susceptibility to chemotherapy-induced hematotoxicity

Pharmacogenomics J. 2018 Apr;18(2):319-330. doi: 10.1038/tpj.2017.23. Epub 2017 Jun 13.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antineoplastic Agents / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols
  • Cyclophosphamide / adverse effects
  • Docetaxel / adverse effects
  • Doxorubicin / adverse effects
  • Female
  • Genetic Background*
  • Genetic Predisposition to Disease / genetics*
  • Hematologic Diseases / chemically induced*
  • Hematologic Diseases / genetics*
  • Humans
  • Male
  • Mice
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Inbred NOD
  • Random Allocation


  • Antineoplastic Agents
  • Docetaxel
  • Doxorubicin
  • Cyclophosphamide