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目的:研究慢性淋巴细胞白血病(CLL)患者分子遗传学异常情况及其预后价值。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)技术和常规细胞遗传学(CC)方法对75例初治CLL患者进行检测,并分析P53、D13S25、ATM基因缺失与临床指标及FC(氟达拉滨加环磷酰胺)方案化疗疗效之间的相关性。结果:CC结果显示12.8%患者有核型异常,5例未见核分裂相;FISH结果发现58.7%患者有基因异常,其中21.3%伴有P53基因缺失,29.3%伴有D13S25基因缺失,16%伴有ATM基因缺失,8.0%为复杂基因组异常。32例患者接受FC方案化疗,P53基因阴性组与阳性组完全缓解(CR)率分别为48.0%和0(P=0.029);D13S25基因阴性组与阳性组CR率分别为39.1%和33.3%(P=1.000);ATM基因阴性组与阳性组CR率分别为50%和0(P=0.014)。ATM基因缺失与患者血红蛋白水平具有相关性(P=0.019),且易出现广泛淋巴结肿大(P=0.010);而P53、D13S25、ATM基因缺失与其他临床指标如性别、年龄、骨髓及外周血淋巴细胞计数、乳酸脱氢酶(LDH)、β-微球蛋白(β-MG)及Binet分期无明显相关性。结论:FISH较CC更能有效检出CLL患者的分子遗传学异常;FC方案对伴有P53、ATM基因缺失的患者疗效差,而对D13S25缺失患者疗效较好;但FISH检测的分子遗传学异常对CLL患者的预后意义尚需进一步扩大样本数及长期随访观察。
Objective: To study the abnormalities of molecular genetics and its prognostic value in patients with chronic lymphocytic leukemia (CLL). METHODS: P53, D13S25, and ATM gene sequence-specific DNA probes were used to detect 75 untreated CLL patients by fluorescence in situ hybridization (FISH) and conventional cytogenetics (CC) methods. P53 and D13S25 were analyzed. Relationship between ATM gene deletion and clinical indicators and chemotherapy efficacy of FC (fludarabine plus cyclophosphamide) regimen. Results: CC results showed that 12.8% of patients had karyotype abnormalities, and 5 cases had no mitotic phase; FISH results found that 58.7% of patients had a genetic abnormality, 21.3% of which had a deletion of P53 gene, 29.3% had a deletion of D13S25 gene, and 16% had There are ATM gene deletions, and 8.0% are complex genomic abnormalities. Thirty-two patients received FC regimen chemotherapy. Complete remission (CR) rates were 48.0% and 0 (P=0.029) in the P53 negative and positive groups, and 39.1% and 33.3% in the D13S25 negative and positive groups, respectively ( P = 1.000); CR rates were 50% in the ATM negative group and 0 in the positive group (P = 0.014). The deletion of ATM gene was correlated with the hemoglobin level of patients (P=0.019), and extensive lymphadenopathy (P=0.010) was prone to occur. However, the deletion of P53, D13S25, and ATM genes and other clinical indicators such as gender, age, bone marrow, and peripheral blood Lymphocyte count, lactate dehydrogenase (LDH), β-microglobulin (β-MG), and Binet stage were not significantly correlated. Conclusion: FISH is more effective than CC in the detection of molecular genetic abnormalities in CLL patients; FC regimen is not effective in patients with deletions of P53 and ATM genes, but is effective in patients with D13S25 deletion; however, molecular genetic abnormalities detected by FISH The prognostic significance of CLL patients needs to further expand the number of samples and long-term follow-up observations.