Wang Runan, Wang Wenliang, Liu Xuan, Wang Huan, Zhang Bin, Li Shuang, Zhang Haining, Yang Jiawei, Zhao Jishun, He Qiuying, Zhang Jihong, Liu Danping, Hao Liangchun
Department of Pediatrics, Shengjing Hospital of China Medical University, Shengyang, Liangning, China.
Precision Targeted Therapy Discovery Center, Institute of Technology Innovation, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, Anhui, China.
Front Oncol. 2023 Jan 31;12:1018250. doi: 10.3389/fonc.2022.1018250. eCollection 2022.
mutations are associated with poor prognosis in the vast majority of cancers. In this study, we present a pediatric B-cell acute lymphoblastic leukemia (B-ALL) patient carrying a rare c.C275T mutation. This extremely rare mutation affects an amino acid residue located between the TAD domain and the DNA-binding domain of p53. The patient was resistant to most conventional chemotherapy regimens and remained minimal residual disease (MRD)-positive after five rounds of such regimens. We tested the sensitivity of the patient's leukemic cells to 21 anti-cancer drugs by performing drug sensitivity assays. The results showed that bortezomib had a very strong killing effect on the patient's leukemic cells. Therefore, we subsequently treated the patient with bortezomib combined with vindesine, cytarabine, and fludarabine. After one course of treatment, the patient became MRD-negative, and there was no recurrence during a 9-month follow-up. In conclusion, our report suggests that the c.C275T mutation is associated with poor prognosis in B-ALL. Fortunately, bortezomib combined with chemotherapy could achieve a better therapeutic effect than conventional regimens in this type of ALL.
在绝大多数癌症中，突变与预后不良相关。在本研究中，我们报告了一名患有罕见的c.C275T突变的小儿B细胞急性淋巴细胞白血病（B-ALL）患者。这种极其罕见的突变影响位于p53的TAD结构域和DNA结合结构域之间的一个氨基酸残基。该患者对大多数传统化疗方案耐药，在经过五轮此类方案治疗后仍为微小残留病（MRD）阳性。我们通过进行药敏试验检测了该患者白血病细胞对21种抗癌药物的敏感性。结果显示硼替佐米对该患者的白血病细胞有非常强的杀伤作用。因此，我们随后用硼替佐米联合长春地辛、阿糖胞苷和氟达拉滨对该患者进行治疗。经过一个疗程的治疗，患者变为MRD阴性，在9个月的随访期间未复发。总之，我们的报告表明c.C275T突变与B-ALL的预后不良相关。幸运的是，在这种类型的ALL中，硼替佐米联合化疗比传统方案能取得更好的治疗效果。
