title: Clinical significance of in vivo cytarabine-induced gene expression signature in AML.
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.
authors.affiliation: a Pharmacotherapy and Translational Research, University of Florida , Gainesville , FL , USA .
authors.forename: Jatinder K
authors.initials: JK
authors.lastname: Lamba
authors.affiliation: b Biostatistics, St Jude Children's Research Hospital , Memphis , TN , USA .
authors.forename: Stanley
authors.initials: S
authors.lastname: Pounds
authors.affiliation: b Biostatistics, St Jude Children's Research Hospital , Memphis , TN , USA .
authors.forename: Xueyuan
authors.initials: X
authors.lastname: Cao
authors.affiliation: c Pharmaceutical Sciences, St Jude Children's Research Hospital , Memphis , TN , USA .
authors.forename: Kristine R
authors.initials: KR
authors.lastname: Crews
authors.affiliation: d Division of Hematology and Oncology, Department of Medicine , University of Florida , Gainesville , FL , USA .
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Cogle
authors.affiliation: a Pharmacotherapy and Translational Research, University of Florida , Gainesville , FL , USA .
authors.forename: Neha
authors.initials: N
authors.lastname: Bhise
authors.affiliation: e Pathology, St Jude Children's Research Hospital , Memphis , TN , USA , and.
authors.forename: Susana C
authors.initials: SC
authors.lastname: Raimondi
authors.affiliation: e Pathology, St Jude Children's Research Hospital , Memphis , TN , USA , and.
authors.forename: James R
authors.initials: JR
authors.lastname: Downing
authors.affiliation: c Pharmaceutical Sciences, St Jude Children's Research Hospital , Memphis , TN , USA .
authors.forename: Sharyn D
authors.initials: SD
authors.lastname: Baker
authors.affiliation: f Oncology, St Jude Children's Research Hospital , Memphis , TN , USA.
authors.forename: Raul C
authors.initials: RC
authors.lastname: Ribeiro
authors.affiliation: f Oncology, St Jude Children's Research Hospital , Memphis , TN , USA.
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Rubnitz
mesh_terms: D000293:Adolescent; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D003561:Cytarabine / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects*; D055785:Gene Knockdown Techniques; D053263:Gene Regulatory Networks; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D015203:Reproducibility of Results; D059467:Transcriptome; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D034741:RNA, Small Interfering; D003561:Cytarabine
keywords: Cytarabine; acute myeloid leukemia; event-free survival; gene expression