Objective: To investigate the clinical and prognostic significance of ABO promotor methylation level in adult patients with leukemia and myelodydysplastic syndrome(MDS). Methods: ABO promoter methylation level of 182 malignant hematological disease patients and 68 normal controls were detected by bisulfite sequencing PCR.Then clinical features and outcome were compared between hypermethylation group and hypomethylation group. Results: The median methylation rate of ABO promoter in newly diagnosed acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL) were 46.98% and 11.01% respectively, which were both higher than that in controls (2.30%, P<0.05). The methylation rates in remission AML and ALL were 1.58% and 2.30% respectively, which were comparable with that in normal group (P>0.05). As to relapse AML and ALL, methylation rates were 41.26% and 17.50% respectively, also significantly higher than that in controls (P<0.05).In patients with chronic myeloid leukemia (CML) chronic phase, the median methylation rate was 1.00%, which was similar to normal group. But a CML patient who transformed to ALL hadextremely high methylation rate 92.56%. The median methylation rate in patients with MDS significantly elevated as 5.81% compared with that in controls (P<0.05). The median overall survival (OS) of ALL and AML (non-M3) patients with hypermethylation were 12.5 months and 15.3 months, which were significantly shorter than those with hypomethylation (24.0 months and 20.0 months)(P<0.05).The median disease-free survival (DFS) of ALL and AML (non-M3) patients with hypermethylation were 9.9 months and 12.0 months, which were significantly shorter than those with hypomethylation (22.3 months and 18.5 months), (P<0.05). Multivariable analysis suggested that ABO promoter methylation level was an independent predictive factor of OS and DFS in ALL and AML (non-M(3)) patients. Conclusion: ABO promoter hypermethylation is closely related to genesis, development and prognosis of leukemia and MDS. Hypermethylationis related to a clinical poor prognosis compare with hypomethylation.
目的： 探讨ABO血型基因启动子（简称ABO启动子）甲基化水平在成人白血病和骨髓增生异常综合征（MPS）中的临床意义及其对预后的影响。 方法： 采用亚硫酸氢盐测序法检测182例成人恶性血液病患者和68例正常对照者的ABO启动子甲基化水平，并对比ABO启动子高甲基化患者和低甲基化患者的临床特征和预后差异。 结果： （1）初治急性淋巴细胞白血病（ALL）和急性髓系白血病（AML）患者ABO启动子中位甲基化率分别为46.98%和11.01%，明显高于正常对照组（2.30%)，P<0.05；ALL、AML缓解期患者中位甲基化率分别为1.58%和2.30%，与正常对照组差异无统计学意义，P>0.05；其复发患者中位甲基化率分别为41.26%和17.50%，明显高于正常对照组，P<0.05。慢性髓性白血病（CML）慢性期患者的中位甲基化率（1.00%）与正常对照组的差异无统计学意义，P>0.05，1例急性淋巴细胞白血病转变患者的甲基化率为92.56%。MDS患者中位甲基化率为5.81%，高于正常对照组，P<0.05。（2）ALL患者中ABO启动子高甲基化组的骨髓白血病细胞水平明显高于低甲基化组[（92.64±4.95）%比（77.30±16.41）%, P<0.05]，其他临床特征对比无明显差异。AML患者ABO启动子高甲基化组和低甲基化组的各临床特征的差异均无统计学意义。（3）ALL和AML（除M(3)型）高甲基化组的中位总生存（OS）期分别为12.5个月和15.3个月，均明显低于各自的低甲基化组（24.0个月和20.0个月），P均<0.05；ALL和AML（除M(3)型）高甲基化组的中位无病生存（DFS）期分别为9.9个月和12.0个月，明显低于低甲基化组（22.3个月和18.5个月），P<0.05。多因素分析显示，ABO启动子甲基化水平是影响ALL和AML（除M(3)型）患者OS和DFS的独立预后因素。 结论： ABO启动子高甲基化与白血病和MDS的发生发展和预后密切相关，ABO启动子甲基化水平高的白血病和MDS患者预后较差。.
Keywords: ABO blood group system; Leukemia; Methylation; Prognosis.