A set of myelodysplasia-related (MDS-R) gene mutations are incorporated into the 2022 European LeukemiaNet risk classification as adverse genetic factors for acute myeloid leukemia (AML) based on their poor prognostic impact on older patients. The impact of these mutations on younger patients (age < 60 years) remains elusive. In the study of 1213 patients with de novo non-M3 AML, we identified MDS-R mutations in 32.7% of the total cohort, 44.9% of older patients and 23.4% of younger patients. The patients with MDS-R mutations had a significantly lower complete remission rate in both younger and older age groups. With a median follow-up of 9.2 years, the MDS-R group experienced shorter overall survival (P = 0.034 for older and 0.035 for younger patients) and event-free survival (P = 0.004 for older and 0.042 for younger patients). Furthermore, patients with MDS-R mutations more frequently harbored measurable residual disease that was detectable using next generation sequencing at morphological CR than those without MDS-R mutations. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) might ameliorate the negative impact of MDS-R mutations. In summary, AML patients with MDS-R mutations have significantly poorer outcomes regardless of age. More intensive treatment, such as allo-HSCT and/or novel therapies, is warranted for AML patients with MDS-R mutations.
一组骨髓增生异常相关基因突变因其对老年患者的不良预后影响，已被纳入2022年欧洲白血病网风险分类作为急性髓系白血病的不良遗传因素。这些突变对年轻患者（年龄＜60岁）的影响尚不明确。在对1213例新发非M3型急性髓系白血病患者的研究中，我们发现全队列中32.7%的患者存在骨髓增生异常相关基因突变，其中老年患者占44.9%，年轻患者占23.4%。携带该突变的患者在年轻组和老年组中完全缓解率均显著降低。中位随访9.2年后，携带骨髓增生异常相关基因突变的患者总生存期（老年组P=0.034，年轻组P=0.035）和无事件生存期（老年组P=0.004，年轻组P=0.042）均更短。此外，与未携带该突变的患者相比，携带者在达到形态学完全缓解时，通过二代测序检测出可测量残留病的频率更高。异基因造血干细胞移植可能改善骨髓增生异常相关基因突变带来的负面影响。综上所述，携带骨髓增生异常相关基因突变的急性髓系白血病患者无论年龄大小，预后均显著更差。对此类患者确有必要采取更强化的治疗，如异基因造血干细胞移植和/或新型疗法。
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