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Abstract
Despite initial remission, ∼60–70% of adult and 30% of pediatric patients experience relapse or refractory AML. Studies so far have identified base line gene expression profiles of pathogenic and prognostic significance in AML; however, the extent of change in gene expression post-initiation of treatment has not been investigated. Exposure of leukemic cells to chemotherapeutic agents such as cytarabine, a mainstay of AML chemotherapy, can trigger adaptive response by influencing leukemic cell transcriptome and, hence, development of resistance or refractory disease. It is, however, challenging to perform such a study due to lack of availability of specimens post-drug treatment. The primary objective of this study was to identify in vivo cytarabine-induced changes in leukemia cell transcriptome and to evaluate their impact on clinical outcome. The results highlight genes relevant to cytarabine resistance and support the concept of targeting cytarabine-induced genes as a means of improving response.
Acknowledgements
E. Coustan-Smith and D. Campana performed the MRD studies; we are thankful to them for sharing the MRD data. We gratefully acknowledge the technical support of E. Wuitschick, M. Griffin and S. Orwick and the database assistance of N. Kornegay and M. Wilkinson. This work was supported in part by NIH P30CA021765 (St Jude), NIH/NCI R01CA132946 (Lamba and Pounds) American Society of Hematology Bridge funding award (Lamba) and by the American Lebanese Syrian Associated Charities (ALSAC). The Leukemia & Lymphoma Society supported C.R.C. with a Scholar in Clinical Research award (2400-13) and a Quest for Cures grant (0725-14).
Potential conflict of interest
Disclosure forms provided by the authors are available with the full text of this article at http://dx.doi.org/10.3109/10428194.2015.1086918
Supplementary materials available online.