Abstract:OBJECTIVE: To investigate the expression of homeobox gene HOXA9 in the bone marrow mononuclear cells of children with acute leukemia (AL) and its clinical significance. METHODS: Forty-six children with AL were divided into acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) groups. Fifteen children with idiopathic thrombocytopenic purpura were selected as a control group. The mRNA expression of HOXA9 was measured by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: HOXA9 expression was detected in 63% of the 52 bone marrow samples from 46 AL children. The positive HOXA9 expression rate in the AML group was significantly higher than in the ALL and control groups (86% vs 35% and 13%; P0.05). The non-remission subgroup had significantly higher HOXA9 expression than the remission subgroup and control group (P<0.05). CONCLISONS: High expression of HOXA9 is associated with the occurrence of AL, and its expression level is significantly higher in children with AML than in those with ALL. There is a positive correlation between the expression level of HOXA9 and the risk of childhood leukemia, and high expression of HOXA9 suggests poor prognosis. Therefore, HOXA9 can be used as one of the indices in the diagnosis, treatment and prognosis prediction of childhood AL.
JIA Xiu-Hong,ZHU Li-Ping,LI Jian-Chang et al. Expression of homeobox gene HOXA9 in childhood acute leukemia, and its clinical significance[J]. CJCP, 2013, 15(4): 268-272.
[1]Borrow J, Shearman AM, Stanton VP Jr, Becher R, Collins T, Williams AJ, et al. The t(7;11) (p15;p15) translocation in acute myeloid leukaemia fuses the genes for nucleoporin NUP98 and class I homeoprotein HOXA9[J]. Nat Genet, 1996, 12(2):159-167.
[2]Huang Y, Sitwala K, Bronstein J, Sanders D, Dandekar M, Collins C, et al. Identification and characterization of Hoxa9 binding sites in hematopoietic cells[J]. Blood, 2012, 119(2):388-398.
[4]Meshinchi S, Arceci RJ. Prognostic factors and risk-based therapy in pediatric acute myeloid leukemia[J]. Oncologist, 2007, 12(3): 341-355.
[5]Niini T, Vettenranta K, Hollmén J, Larramendy ML, Aalto Y, Wikman H, et al. Expression of myeloid-specific genes in childhood acute lymphoblastic leukemia-a cDNA array study[J]. Leukemia, 2002, 16(11): 2213-2221.
[6]Casas S, Nagy B, Elonen E, Aventín A, Larramendy ML, Sierra J, et al. Aberrant expression of HOXA9, DEK, CBL and CSF1R in acute myeloid leukemia[J]. Leuk Lymphoma, 2003, 44(11): 1935-1941.
[7]Thompson A, Quinn MF, Grimwade D, O′Neill CM, Ahmed MR, Grimes S, et al. Global down-regulation of HOX gene expression in PML-RARalpha+ acute promyelocytic leukemia identified by small-array real-time PCR[J]. Blood, 2003, 101(4): 1558-1565.
[8]Long J, Parkin B, Ouillette P, Bixby D, Shedden K, Erba H, et al. Multiple distinct molecular mechanisms influence sensitivity and resistance to MDM2 inhibitors in adult acute myelogenous leukemia[J]. Blood, 2010, 116(1): 71-80.
[10]Starkova J, Zamostna B, Mejstrikova E, Krejci R, Drabkin HA, Trka J. HOX gene expression in phenotypic and genotypic subgroups and low HOXA gene expression as an adverse prognostic factor in pediatric ALL[J].Pediatr Blood Cancer, 2010, 55(6): 1072-1082.
[11]Andreeff M, Ruvolo V, Gadgil S, Zeng C, Coombes K, Chen W, et al. HOX expression patterns identify a common signature for favorable AML[J]. Leukemia, 2008, 22(11): 2041-2047.