194例CML患者染色体核型及ABL激酶区突变检测的临床意义分析

发布时间：2018-04-02 12:36

本文选题：慢性粒细胞性白血病　切入点：染色体核型　出处：《兰州大学》2017年硕士论文

【摘要】：目的:通过收集我院血液科2010~2016年确诊的194例CML患者的临床资料,分析CML患者的临床特征、染色体核型、ABL激酶区突变,探讨CML染色体异常的特征、ABL激酶区突变的检测及临床意义。方法:我们回顾性分析我院血液科2010~2016年确诊的194例CML患者,收集患者临床及实验室资料,包括性别、年龄、外周血细胞计数、脾脏大小、骨髓细胞形态学检查、荧光原位杂交技术检测BCR-ABL融合基因、G显带技术进行染色体核型分析、RQ-PCR方法检测BCR-ABL基因水平及对所需患者治疗后行ABL激酶区突变检测;根据以上检查结果对疾病进行分期及危险度分层。根据2009年Baccarani IM耐药标准,其中37例为伊马替尼耐药患者,并收集此类患者IM治疗前病史及干扰素使用情况。结果:194例CML患者中182例(93.81%)为Ph+,Ph+患者中167例(91.76%)有典型t(9;22)(q34;q11),12例(6.19%)为Ph-(FISH和/或PCR检测存在BCR-ABL融合基因)。本研究参照2009年Baccarani IM耐药标准,194例CML患者中,有37例为IM耐药患者,其中慢性期18例,占耐药患者的48.6%,加速期/急变期19例,占51.35%。37例耐药患者IM治疗前中位病程3.5年,持续完全分子生物学缓解患者中有8例在接受IM治疗前使用干扰素和/或羟基脲治疗,其中位病程0.65年,有统计学差异(p=0.016)。耐药患者接受干扰素治疗中位时间为2.95±2.2年,持续完全分子生物学缓解患者中有5例在使用IM治疗前使用干扰素治疗,其中位时间为1.5±1.97年,无统计学差异(p=0.176)。在本研究194例CML患者中有48例接受了ABL激酶区突变检测。37例耐药患者中,有6例检出ABL激酶区突变,突变率为16.22%;18例慢性期患者中2例存在突变,比例为(11%),19例加速期/急变期患者中4例存在突变(21.1%),无明显统计学差异(p=0.672)。其中P-loop区域突变2例,其他区域:F317L、L298V、E459K、M351T各1例。结论:加速期和急变期CML患者更容易出现变异易位和/或附加染色体异常;接受IM治疗前病程越长,患者发生耐药的可能性越大;使用二代TKIs治疗患者也可发生ABL激酶区突变。
[Abstract]:Objective: to collect the clinical data of 194 patients with CML diagnosed in hematology department of our hospital from 2010 to 2016, and to analyze the clinical characteristics of CML patients and the mutation of chromosome karyotype in ABL kinase region. Methods: we retrospectively analyzed 194 patients with CML diagnosed from 2010 to 2016, and collected clinical and laboratory data, including sex and age. Peripheral blood cell count, spleen size, bone marrow cell morphology, BCR-ABL fusion gene G banding was detected by fluorescence in situ hybridization. Karyotype analysis was performed. RQ-PCR was used to detect the level of BCR-ABL gene and ABL kinase region mutation was detected after treatment. According to the Baccarani IM criteria of 2009, 37 of them were imatinib resistant. The history of IM before treatment and the use of interferon in these patients were collected. Results 182 out of 194 patients with CML were diagnosed as Ph Ph patients. 167 patients with Ph Ph had typical tachycardia 922, Q34, Q11C, 12 cases.) BCR-ABL fusion gene was found in the detection of Ph-(FISH and / or PCR. This study refers to the presence of BCR-ABL fusion gene in the detection of Ph-(FISH and / or PCR. In 194cases of CML patients with Baccarani IM resistance standard, There were 37 cases of IM resistance, including 18 cases of chronic phase, accounting for 48.6% of the drug resistant patients, 19 cases of accelerated phase / acute phase, accounting for 51.35% of 37 patients with resistance to IM before the treatment of the median duration of 3.5 years. Eight of the patients with continuous complete molecular biological remission were treated with interferon and / or hydroxyurea before IM treatment. The mean time of interferon therapy was 2.95 卤2.2 years. Five of the patients with continuous complete molecular biological remission were treated with interferon before IM therapy, with a bit time of 1.5 卤1.97 years. There was no statistical difference between 0.176% and 0.176%. In this study, 48 of the 194 CML patients received ABL kinase region mutation detection. 6 of 37 drug resistant patients detected ABL kinase region mutation, the mutation rate was 16.22% of 18 chronic phase patients, 2 of the 18 chronic phase patients had mutation. There was no significant difference in the mutation of P-loop region in 4 of the 19 patients at the accelerated / acute phase, and there was no significant difference between the two groups. 2 of the 19 patients with P-loop region had mutation in the P-loop region, and there was no significant difference between the two patients and the control group, and there was no significant difference between the two patients. Other regions: one case of E459KN M351T in the other regions: F317LU L298VU E459KN M351T. Conclusion: the patients with CML in accelerated phase and in acute phase are more likely to have aberrant translocation and / or additional chromosomal abnormalities, and the longer the course of treatment is before IM, the more likely the patient is to develop drug resistance. Mutations in the ABL kinase region may also occur in patients treated with second generation TKIs.
【学位授予单位】：兰州大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R733.72

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