目前的研究受到对慢性粒单核细胞白血病（CMML；N = 398）机构队列的探索性分析的启发，该分析显示七名植物同源结构域指蛋白6（PHF6）突变（PHF6MUT）患者没有原始细胞转化的情况。随后 Mayo Clinic 企业范围内的数据库搜索又发现了 28 例 PHF6MUT 病例。与野生型 PHF6 对应物 (PHF6WT; N = 391) 相比，PHF6MUT 病例 (N = 35) 更有可能共表达 TET2 (89% vs. 45%; p < .01)、RUNX1 (29% vs. 14%；p = .03)、CBL（14% vs. 2%；p < .01）和 U2AF1（17% vs. 6%；p = .04）以及不太可能的 SRSF2（23% vs. 45） %; p < .01) 突变。他们也更有可能表现出 Y 染色体丢失（LoY；21% vs. 2%；p< .01）和血小板 <100 × 109/L（83% vs. 51%；p< .01）。多变量分析确定 PHF6MUT（HR 0.28，95% CI 0.15-0.50）和 DNMT3AMUT（HR 5.8，95% CI 3.3-10.5）是总体生存的最强分子预测因子。无母细胞转化存活率也是如此，相应的 HR (95% CI) 为 0.08 (0.01-0.6) 和 9.5 (3.8-23.5)。在中位 20 个月的随访中，33 名 PHF6MUT/DNMT3AWT 患者均未记录到母细胞转化，但 19 名 DNMT3AMUT 患者中有 6 名 (32%) 发生了母细胞转化，374 名 PHF6WT/DNMT3AWT 患者中有 74 名 (20%) 发生母细胞转化 (p < .01 ）。特定的分子特征在 CMML 特定分子预后模型 (CPSS-mol) 的背景下维持了其显着的预测性能。 PHF6MUT 识别出一个独特的 CMML 患者亚群，其特征是血小板减少、LoY 患病率较高和预后良好。© 2024 作者。 《美国血液学杂志》由 Wiley periodicals LLC 出版。

The current study was inspired by observations from exploratory analyses of an institutional cohort with chronic myelomonocytic leukemia (CMML; N = 398) that revealed no instances of blast transformation in the seven patients with plant homeodomain finger protein 6 (PHF6) mutation (PHF6MUT). A subsequent Mayo Clinic enterprise-wide database search identified 28 more cases with PHF6MUT. Compared with their wild-type PHF6 counterparts (PHF6WT; N = 391), PHF6MUT cases (N = 35) were more likely to co-express TET2 (89% vs. 45%; p < .01), RUNX1 (29% vs. 14%; p = .03), CBL (14% vs. 2%; p < .01), and U2AF1 (17% vs. 6%; p = .04) and less likely SRSF2 (23% vs. 45%; p < .01) mutation. They were also more likely to display loss of Y chromosome (LoY; 21% vs. 2%; p < .01) and platelets <100 × 109/L (83% vs. 51%; p < .01). Multivariable analysis identified PHF6MUT (HR 0.28, 95% CI 0.15-0.50) and DNMT3AMUT (HR 5.8, 95% CI 3.3-10.5) as the strongest molecular predictors of overall survival. The same was true for blast transformation-free survival with corresponding HR (95% CI) of 0.08 (0.01-0.6) and 9.5 (3.8-23.5). At median 20 months follow-up, blast transformation was documented in none of the 33 patients with PHF6MUT/DNMT3AWT but in 6 (32%) of 19 with DNMT3AMUT and 74 (20%) of 374 with PHF6WT/DNMT3AWT (p < .01). The specific molecular signatures sustained their significant predictive performance in the context of the CMML-specific molecular prognostic model (CPSS-mol). PHF6MUT identifies a unique subset of patients with CMML characterized by thrombocytopenia, higher prevalence of LoY, and superior prognosis.© 2024 The Author(s). American Journal of Hematology published by Wiley Periodicals LLC.