Expression of SIRT1 in bone marrow biopsy tissues and its clinical significance among children with acute myeloid leukemia
LIU Xiao-Ming1, ZHOU Jian-Feng1, ZHANG Pei-Hong2, RUAN Min1, ZHANG Li1, ZOU Yao1, CHEN Yu-Mei1, ZHU Xiao-Fan1
Department of Pediatrics, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking University Mediacal Colloge, Tianjin 300020, China
Abstract:Objective To determine the expression level of silent mating-type information regulation 2 homologue 1 (SIRT1) in bone marrow biopsy tissues among children with acute myeloid leukemia (AML) and analyze its relationship with the prognosis of AML patients. Methods A retrospective analysis was performed on the clinical data of 54 children who were diagnosed with AML between July 2009 and April 2012 and who underwent bone marrow biopsy at diagnosis. The expression of SIRT1 in bone marrow was measured by immunohistochemistry. The 54 patients were divided into two groups according to the expression of SIRT1: SIRT1-negative (n=10) and SIRT1- positive (n=44). The SIRT1-positive group was further divided into three subgroups: SIRT1(+) (n=8), SIRT1(++) (n=7) and SIRT1(+++) (n=29) according to the expression levels of SIRT1. Cox multivariate regression analysis was used to determine the unfavorable factors for long survival in children with AML. Results The SIRT1(+++) subgroup had a significantly higher mortality than the SIRT1-negative group (PPPCI: 1.017-4.219; P=0.045). Conclusions SIRT1 is overexpressed in some of pediatric AML patients, and the overexpression of SIRT1 is associated with poor prognosis.
LIU Xiao-Ming,ZHOU Jian-Feng,ZHANG Pei-Hong et al. Expression of SIRT1 in bone marrow biopsy tissues and its clinical significance among children with acute myeloid leukemia[J]. CJCP, 2014, 16(6): 614-618.
Vardiman JW, Thiele J, Arber DA, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes[J].Blood, 2009, 114(5): 937-951.
[2]
Huffman DM, Grizzle WE, Bamman MM, et al. SIRT1 is significantly elevated in mouse and human prostate cancer[J].Cancer Res, 2007, 67(14): 6612-6618.
[3]
Stunkel W, Peh BK, Tan YC, et al. Function of the SIRT1 protein deacetylase in cancer[J].Biotechnol J, 2007, 2(11): 1360-1368.
[4]
Firestein R, Blander G, Michan S, et al. The SIRT1 deacetylase suppresses intestinal tumorigenesis and colon cancer growth[J].PLoS ONE, 2008, 3(4): e2020.
[5]
Chen W, Bhatia R. Roles of SIRT1 in leukemogenesis[J].Curr Opin Hematol, 2013, 20(4): 308-313.
[6]
Bradbury CA, Khanim FL, Hayden R, et al. Histone deacetylases in acute myeloid leukaemia show a distinctive pattern of expression that changes selectively in response to deacetylase inhibitors[J].Leukemia, 2005, 19(10): 1751-1759.
Tsukimoto I, Tawa A, Horibe K, et al. Risk-stratified therapy and the intensive use of cytarabine improves the outcome in childhood acute myeloid leukemia: the AML99 trial from the Japanese Childhood AML Cooperative Study Group[J].J Clin Oncol, 2009, 27(24): 4007-4013.
Zhang L, Zhu X, Zou Y, et al. Effect of arsenic trioxide on the treatment of children with newly diagnosed acute promyelocytic leukemia in China[J].Int J Hematol, 2011, 93(2): 199-205.
[12]
K n a b e C, K r a s k a B, K o c h C, e t a l. A m e t h o d f o r immunohistochemical detection of osteogenic markers in undecalcified bone sections[J].Biotech Histochem, 2006, 81(1): 31-39.
Knight JR, Milner J. SIRT1, metabolism and cancer[J].Curt Opin Oncol, 2012, 24(1): 68-75.
[15]
Yuan H, Wang Z, Li L, et al. Activation of stress response gene SIRT1 by BCR-ABL promotes leukemogenesis[J].Blood, 2012, 119(8): 1904-1914.
[16]
Li L, Wang L, Wang Z, et al. Activation of p53 by SIRT1 inhibition enhances elimination of CML leukemia stem cells in combination with imatinib[J].Cancer Cell, 2012, 21(2): 266-281.
[17]
O'Hare T, Zabriskie MS, Eiring AM, et al. Pushing the limits of targeted therapy in chronic myeloid leukaemia[J].Nat Rev Cancer, 2012, 12(8): 513-526.