急性髓系白血病患者中“多次打击”与“单次打击”TP53 改变的预后影响：来自髓系恶性肿瘤和肿瘤疾病联盟的结果。
Prognostic impact of 'multi-hit' versus 'single hit' TP53 alteration in patients with acute myeloid leukemia: results from the Consortium on Myeloid Malignancies and Neoplastic Diseases.
发表日期：2024 May 30
作者：
Talha Badar, Ahmad Nanaa, Ehab Atallah, Rory M Shallis, Emily C Craver, Zhuo Li, Aaron D Goldberg, Antoine N Saliba, Anand Patel, Jan P Bewersdorf, Adam Duvall, Madelyn Burkart, Danielle Bradshaw, Yasmin Abaza, Maximilian Stahl, Neil Palmisiano, Guru Subramanian Guru Murthy, Amer M Zeidan, Vamsi Kota, Mrinal M Patnaik, Mark R Litzow
来源：
HAEMATOLOGICA
摘要：
虽然有明确的证据表明，在低风险骨髓增生异常综合征 (MDS) 中，与单次突变 (SH) 相比，多次突变 (MH) TP53 突变的预后较差，但在高风险 MDS 和急性髓系白血病中的数据是相互矛盾的（反洗钱）。我们利用来自 10 个美国学术机构的数据进行了深入分析，以研究 SH (n= 139) 与 MH (n= 243) TP53MTAML 分子特征和结果的差异。与 SH TP53MT AML 相比，复杂细胞遗传学 (CG) 在 MH 中更为常见 (p <0.001)；而 ASXL1 (p= <0.001)、RAS (p<0.001)、剪接因子 (p= 0.003)、IDH1/2 (p= 0.001)、FLT3 ITD (p= <0.001) 和 NPM1 (p= 0.005) 突变显着与 SH TP53MT AML 聚集。排除仅接受最佳支持治疗的患者后，SH 和 MH 之间的生存率令人沮丧，但没有显着差异（无事件生存期 [EFS]：分别为 3.0 个月与 2.20 个月，p= 0.22/总生存期 [OS]：8.50 个月与 7.53 个月， p = 0.13）。在多变量分析中，IDH1 突变和同种异体造血干细胞移植 (allo-HCT) 作为时间依赖性协变量与较高的 EFS 相关（HR；0.44，95% CI：0.19-1.01，p= 0.05/HR；0.34，95 % CI：0.18-0.62，p<0.001）和 OS（HR；0.24，95% CI：0.08-0.71，p= 0.01/HR；0.28，95% CI：0.16-0.47，p<0.001）。而复杂 CG（HR；1.56，95% CI：1.01-2.40，p= 0.04）对 OS 仍具有不利的意义。我们的分析表明，与 MDS 不同，多重命中 TP53MT 在独立预测 AML 患者的结局方面不太相关。
While there is clear evidence to suggest poorer outcome associated with multi-hit (MH) TP53 mutation compared to single-hit (SH) in lower-risk myelodysplastic syndrome (MDS), data are conflicting in both higher-risk MDS and acute myeloid leukemia (AML). We conducted an indepth analysis utilizing data from 10 US academic institutions to study differences in molecular characteristics and outcomes of SH (n= 139) versus MH (n= 243) TP53MTAML. Complex cytogenetics (CG) were more common in MH compared to SH TP53MT AML (p <0.001); whereas ASXL1 (p= <0.001), RAS (p<0.001), splicing factor (p= 0.003), IDH1/2 (p= 0.001), FLT3 ITD (p= <0.001) and NPM1 (p= 0.005) mutations significantly clustered with SH TP53MT AML. Survival after excluding patients who received best supportive care alone was dismal but not significantly different between SH and MH (event free survival [EFS]: 3.0 vs 2.20 months, p= 0.22/ overall survival [OS]: 8.50 vs 7.53 months, respectively, p= 0.13). In multivariable analysis, IDH1 mutation and allogeneic hematopoietic stem cell transplantation (allo-HCT) as a time-dependent covariate were associated with superior EFS (HR; 0.44, 95% CI: 0.19-1.01, p= 0.05/ HR; 0.34, 95% CI: 0.18-0.62, p<0.001) and OS (HR; 0.24, 95% CI: 0.08-0.71, p= 0.01/ HR; 0.28, 95% CI: 0.16-0.47, p<0.001). While complex CG (HR; 1.56, 95% CI: 1.01-2.40, p= 0.04) retained unfavorable significance for OS. Our analysis suggests that unlike in MDS, multihit TP53MT is less relevant in independently predicting outcomes in patients with AML.