Lili Pan , Yining Li , Huiying Gao , Xiaolin Lai , Yuanhua Cai , Zhixiang Chen , Xiaofan Li , Shao-yuan Wang
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引用次数: 0
Abstract
Familial acute myeloid leukemia (AML) pedigrees with germline CCAAT/enhancer-binding protein-α (CEBPA) mutation have been rarely reported due to insufficient knowledge of their clinical features. Here, we report two Chinese families with multiple AML cases carrying germline CEBPA mutations, one of which had 11 cases spanning four consecutive generations. Additionally, we collected clinical data of 57 AML patients from 22 families with germline CEBPA mutations, with 58.3% of them harboring double CEBPA mutations. The first mutation frequently occurred at the N-terminal of CEBP/α (78.6%), resulting in an exclusive expression of p30 of CEBPA (CEBPAp30). The second mutation was mostly found at the C-terminal of CEBP/α (CEBPAothers). Germline CEBPAp30 carriers had higher incidences of AML (80.36% vs. 42.86%) and earlier onset of AML (18 vs. 38.5 years old) compared to germline CEBPAothers carriers. Despite the high rates of relapse, most familial AML cases exhibited favorable overall survival (OS), with germline CEBPAp30 carriers having better survival outcomes (>25 years vs. 11 years for CEBPAothers carriers). Among the 27 healthy germline CEBPA-mutated carriers, we detected a pre-leukemia clone harboring a pathogenic IDH2 variant (R140Q)in one individual. These findings should aid in the genetic counseling and management of AML patients and healthy carriers with germline CEBPA mutations.
由于对家族性急性髓性白血病(AML)的临床特征了解不足,目前很少有家族性急性髓性白血病(AML)种系CCAAT/增强子结合蛋白-α(CEBPA)突变的报道。在此,我们报告了两个携带种系CEBPA突变的多发性急性髓细胞性白血病中国家族,其中一个家族连续四代共有11例病例。此外,我们还收集了22个家族中57例AML患者的临床数据,其中58.3%的患者携带双CEBPA突变。第一个突变经常发生在CEBP/α的N端(78.6%),导致CEBPA的p30(CEBPAp30)唯一表达。第二种突变主要发生在 CEBP/α 的 C 端(CEBPAothers)。与种系CEBPAothers携带者相比,种系CEBPAp30携带者的急性髓细胞性白血病发病率更高(80.36%对42.86%),发病年龄更早(18岁对38.5岁)。尽管复发率较高,但大多数家族性急性髓细胞性白血病病例的总生存期(OS)良好,其中种系CEBPAp30携带者的生存期更长(25年对CEBPAothers携带者的11年)。在27名健康的CEBPA基因突变种系携带者中,我们在一名个体中检测到了携带致病性IDH2变异体(R140Q)的白血病前期克隆。这些发现有助于为急性髓细胞性白血病患者和健康的种系CEBPA突变携带者提供遗传咨询和管理。
期刊介绍:
Leukemia Research an international journal which brings comprehensive and current information to all health care professionals involved in basic and applied clinical research in hematological malignancies. The editors encourage the submission of articles relevant to hematological malignancies. The Journal scope includes reporting studies of cellular and molecular biology, genetics, immunology, epidemiology, clinical evaluation, and therapy of these diseases.