单体核型在急性髓系白血病中的遗传学特点及其临床意义

The cytogenetical characterization of monosomal karyotype and its clinical significance in acute myeloid leukemia

目的探讨单体核型(MK)在急性髓系白血病(AML)中的遗传学特点及其临床意义。方法 R显带技术成功分析385例确诊为AML的患者染色体核型,对92例异常核型(低危核型除外)患者的临床和实验室资料进行回顾性分析。结果 MK共29例,占所有AML核型的7.53%(29/385),占异常核型的31.5%(29/92)。93.1%(27/29)为骨髓增生异常(MDS)相关的细胞遗传学异常,常见的核型有复杂核型、-7/7q-、-5/5q-。MK中未发现NPM1突变和FLT3/ITD突变。以不伴MK的异常核型AML患者为对照,MK患者发病年龄偏高(P=0.018),初诊时外周血白细胞数和骨髓原始细胞比例偏低(分别为P=0.037,P=0.012),较多曾有MDS或骨髓增殖性肿瘤病史(P=0.011)。MK患者的中位生存时间明显短于不伴MK的高危核型和中危核型患者(分别为6、17和24个月,P=0.001),而对于剔除MK的高危核型患者,其预后已经接近中危核型组(P=0.454)。结论单体核型AML具有独特的生物学和临床特征。单体核型相对于其他异常核型尤其是高危核型更能提示预后不良,在AML患者中具有重要的预后评估价值。

Objective：To investigate the cytogenetical characterization of monosomal karyotype（MK）and further analyze its clinical significance in acute myeloid leukemia（AML）. Methods：The chromosome karyotypes of patients with 385 newlydiagnosis AML were analysed using R binding technique,which had identified 92 cases with abnormal karyotypes（exclusion of favorable risk group）,for whom the clinical and laboratorial characterization were analysed retrospectively. Results：29 cases were identified as MK. The frequency of MK was 7.53%（29/385）in total AML patients and 31.5%（29/92）in patients with abnormal karyotypes. 27（93.1%）had myelodysplastia（MDS）related cytogenetic changes. The most common abnormality of MK were complex karyotype,-7/7 q-and-5/5 q-. Regarding molecular abnormalities,NPM1 mutation and FLT3-ITD mutation were absent in MK. Compared to cytogenetically abnormal patients without MK,MK patients were associated with older age（P=0.018）,lower white blood counts（P=0.037）and lower percentages of blasts in bone marrow（P=0.012）at diagnosis,while MK patients had a higher frequency（P=0.011）of MDS or myeloproliferative neoplasms history. Survival analysis showed that patients with MK were markedly associated with shorter median overall survival than unfavorable risk group without MK and intermediate risk group（6 months vs 17 months vs 24 months,P=0.001）. Nevertheless,excluding MK,there was no significantly different overall survival between patients with unfavorable karyotype and intermediate karyotype（P=0.454）. Conclusion：Patients with monosomal karyotype in AML have distinct biologic and clinical features. Monosomal karyotype was likely to associate with poorer prognosis than the other abnormal karyotypes especially unfavorable karyotype. Monosomal karyotype should have the important value of predicting prognosis of AML patients.