Significance of NOTCH1 mutations detections in T-acute lymphoblastic leukemia patients
Significance of NOTCH1 mutations detections in T-acute lymphoblastic leukemia patients
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DOI：
10.3233/cbm-190967
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发表时间：
2020-01-01
影响因子：
3.1
通讯作者：
Sabry, Mohamed
中科院分区：
文献类型：
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作者：
Aref, Salah;El Agdar, Mohammed;Sabry, Mohamed
背景：本研究旨在确定 T 细胞急性淋巴细胞白血病 (T-ALL) 患者中神经源性位点缺口同源蛋白 1 (NOTCH1) 突变的患病率和临床影响。 患者和方法：本研究纳入了 60 例 T-ALL 病例队列。对诊断时所有研究的 T ALL 患者中的 NOTCH1 外显子 26、27 和外显子 34 的远端部分进行了桑格测序，扩展了编码转录激活结构域 (TAD) 和富含脯氨酸、谷氨酸、丝氨酸、苏氨酸 (PEST) 结构域的肽序列的序列。 结果：在 60 名 T-ALL 患者中，有 40 名 (66%) 检测到了 NOTCH1 突变。 T-ALL患者的突变为缺失（22个突变）和点突变（10个突变）。 NOTCH1突变对T-ALL的临床结果和预后没有显着影响，包括总生存期、无进展生存期、复发和死亡率（均P>0.05）。结论：NOTCH1突变在T-ALL患者中频繁检测到；然而，这些突变并不影响 T ALL 患者的预后。诊断时NOTCH1突变的高患病率可用于检测T ALL中的微小残留病。
BACKGROUND: This study aimed to determine the prevalence and clinical impact of neurogenic locus notch homolog protein 1 (NOTCH1) mutations among patients with T cell acute lymphoblastic leukemia (T-ALL).PATIENT AND METHODS: A cohort of 60 T-ALL cases was included in this study. Sanger sequencing were done for NOTCH1 exon 26, 27, and distal part of exon 34 expanding the sequences encoding transcription activation domain (TAD) and a peptide sequence rich in proline, glutamic acid, serine, threonine (PEST) domains in all studied T ALL patients at diagnosis.RESULTS: NOTCH1 mutations was detected in 40 out of 60 T-ALL patients (66%). Mutations in T-ALL patients are deletions (22 mutations) and point mutation (10 mutations). NOTCH1 mutations was found to have no significant impact on clinical outcome and prognosis in T-ALL including overall survival, progression free survival, relapse and mortality (P > 0.05 for all).CONCLUSION: NOTCH1 mutations were frequently detected in T All patients; however, these mutations did not affect the T ALL patient's outcome. The high prevalence of NOTCH1 mutations at diagnosis could be used for detection of minimal residual disease in T ALL.