同源盒基因HOXA9在儿童急性白血病中的表达及其临床意义

Expression of homeobox gene HOXA9 in childhood acute leukemia, and its clinical significance

摘要:

目的：研究同源盒基因HOXA9在儿童急性白血病（AL）患儿骨髓单个核细胞中的表达，并探讨其临床意义。方法：采用RT-PCR方法检测46例不同时期AL患儿HOXA9 mRNA的表达水平，以15例特发性血小板减少性紫癜（ITP）患儿作为对照。结果：46例AL患儿（52份骨髓标本）HOXA9基因阳性表达率为63%，其中急性髓细胞白血病(AML)组阳性表达率（86%）明显高于急性淋巴细胞白血病（ALL）组（35%）及对照组（13%）（P<0.05）； AML组HOXA9 mRNA表达水平明显高于ALL组及对照组（P<0.05）。HOXA9在各型儿童AML中表达不同，mRNA相对表达水平依次为：M5型＞M4型＞M1和（或）M2型，而在M3型中未检测到表达。HOXA9在AML患儿高危组中的阳性表达水平较高。AML患儿初治组HOXA9基因阳性表达率及mRNA水平明显高于缓解组和对照组（P<0.05），而缓解组与对照组比较差异无统计学意义；未缓解组HOXA9基因表达显著高于缓解组和对照组（P<0.05）。结论：HOXA9基因高表达与AL的发生相关；AML患儿HOXA9基因表达水平明显高于ALL患儿。HOXA9基因高表达者与白血病危险程度有关，且提示预后不良。因此，HOXA9基因有望成为儿童AL诊断、治疗及判断预后的一个靶点。

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%; P<0.05). The mRNA expression of HOXA9 in the AML group was significantly higher than in the ALL and control groups (P<0.05). Among the children with AML, those with M5 AML had the highest HOXA9 mRNA level, followed by children with M4 AML and children with M1 and/or M2 AML, but HOXA9 expression was not detected in children with M3 AML. The high-risk subgroup of AML children had relatively high levels of HOXA9 expression. In the children with AML, the initial treatment subgroup had significantly higher positive HOXA9 expression rate and HOXA9 mRNA levels than in the remission subgroup and control group (P<0.05), but there were no significant differences between the latter two groups (P>0.05). 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.