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: Jatinder K Lamba, Stanley Pounds, Xueyuan Cao, Kristine R Crews, Christopher R Cogle, Neha Bhise, Susana C Raimondi, James R Downing, Sharyn D Baker, Raul C Ribeiro, Jeffrey E Rubnitz
• Journal: Leukemia & lymphoma (Leuk Lymphoma) Vol. 57 Issue 4 Pg. 909-20 ( 2016) ISSN: 1029-2403 [Electronic] United States
• PMID: 26366682 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antimetabolites, Antineoplastic
• RNA, Small Interfering
• Cytarabine

Topics

• Adolescent
• Antimetabolites, Antineoplastic (pharmacology, therapeutic use)
• Child
• Child, Preschool
• Cytarabine (pharmacology, therapeutic use)
• Female
• Gene Expression Profiling
• Gene Expression Regulation, Leukemic (drug effects)
• Gene Knockdown Techniques
• Gene Regulatory Networks
• Humans
• Leukemia, Myeloid, Acute (drug therapy, genetics, mortality, pathology)
• Male
• RNA Interference
• RNA, Small Interfering (genetics)
• Reproducibility of Results
• Transcriptome
• Treatment Outcome