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FISH检测慢性淋巴细胞白血病P53、D13S25、ATM 基因缺失及其预后价值
作者:高银 方鹏 张国平  
单位:中南大学湘雅医院
关键词:  荧光原位杂交 慢性淋巴细胞白血病 P53基因 D13S25基因 ATM基因  预后  
分类号:
出版年·卷·期(页码):2013·41·第十二期(877-881)
摘要:

目的 研究慢性淋巴细胞白血病(CLL)患者P53、D13S25、ATM基因缺失情况及其预后价值。方法 采用P53、D13S25、ATM基因序列特异性DNA探针,应用荧光原位杂交(FISH)技术对75例初治CLL患者进行检测,分析P53、D13S25、ATM基因缺失在CLL中的发生情况及其与FC方案化疗后疗效之间的相关性。结果 75例CLL患者中,FISH检测58.7%(44/75)有基因异常,其中16例(21.3%)伴有P53基因缺失,22例(29.3%)伴有D13S25基因缺失,12例(16%)伴有ATM基因缺失,6例(8.0%)为复杂基因组异常。32例患者接受FC方案化疗,P53基因阴性组完全缓解率为48.0%(12/25),阳性组均未获得CR(0/7)(P=0.029);D13S25基因阴性组完全缓解率为39.1%(9/23),阳性组完全缓解率为33.3%(3/9)(P=1.000);ATM基因阴性组完全缓解率为50%(12/24),阳性组均未获CR(0/8)(P=0.014)。P53、D13S25、ATM基因缺失与性别、年龄、骨髓及外周血淋巴细胞计数、乳酸脱氢酶、β-MG及Binet分期无明显相关性。结论 FISH可有效检出CLL患者的基因组异常,伴有p53、ATM基因缺失的患者,FC方案治疗疗效差,D13S25缺失患者预后较好;FISH检测p53、D13S25、ATM基因缺失在CLL的临床治疗和预后判断中具有重要价值。

[Abstract] Objective To explore the prognostic significance of P53、D13S25、ATM gene deletion in patients with chronic lymphocytic leukemia(CLL).Methods Interphase fluorescence in situ hybridization (FISH) were used to detect P53、D13S25、ATM gene deletion in 75 patients.P53、D13S25、ATM gene deletion and their association with efficacy of Fludarabine and Cyclophosphamide were analyzed. Results Out of the75 CLL patients,The total incidence of these karyotypic abnormalities is 26.3% by FISH. 。p53 gene deletion was found in 16(21.3%)cases,D13S25 gene deletion in 22(29.3%)cases, ATM gene deletion in 12(16%)cases,Complex karyotype in 6(8%)cases.Among 32 patients who received FC Chemotherapy,none of the 7 cases with p53 gene deletion achieved complete response,while 12 of 25(48.0%) cases without the gene deletion achieved CR(P=0.029); 3 of the 9 (33.3%) cases with D13S25 gene deletion achieved complete response,while 9 of 23(39.1%)cases without the gene deletion achieved CR(P=1.000); none of the 8 cases with ATM gene deletion achieved complete response,while 12 of 24(50%) cases without the gene deletion achieved CR (P=0.014). There was no signifieant differences of P53、D13S25、ATM gene deletion rates in sex,age, peripheral lymphocyte count,and the levels of LDH,32-MG,and Binet stages. Conclusion FISH can effectly detect the chromosomal abnormalities of CLL. CLL patients with p53 and/or ATM gene deletion had poor therapeutic effect,and hence poor prognosis,while who with D13S25 gene deletion had better therapeutic effect. These gene deletions have important prognostic value.

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