Liu Jie, Han WenMin, Cai Xiaohui, Wang Zheng, Cao LiuJun, Hua HaiYing, Jia ZhuXia, Chao HongYing, Lu XuZhang, Shen HongJie
Department of Hematology, Affiliated Changzhou Second Hospital of Nanjing Medical University, Changzhou, People's Republic of China.
Department of Hematology, The First Affiliated Hospital of NanJing Medical University, Nanjing, People's Republic of China.
Hematology. 2022 Dec;27(1):565-574. doi: 10.1080/16078454.2022.2071799.
The aim of the study was to determine molecular genetic and clinical characterization of acute myeloid leukemia (AML) with trisomy 8 as the sole chromosome abnormality, a recurrent but rare chromosomal abnormality in AML.
Interphase fluorescence in situ hybridization, reverse transcriptase-quantitative polymerase chain reaction for gene rearrangement and next-generation sequencing (NGS) were performed on sole trisomy 8 AML patients.
A total of 35 AML patients with trisomy 8 as the sole chromosome abnormality were screened. The most frequently mutated genes were (37.1%), (28.6%), -ITD(28.6%), (22.9%), (17.1%), and (14.3%). The sole +8 AML patients exhibited more mutations in (28.6% . 4.8%, = 0.001) and (14.3% . 4.8%, = 0.039) by comparing with normal karyotype AML (NK AML) patients(= 63). The sole +8 AML patients( = 35) with or mutations showed significantly lower WBC counts, while -ITD showed higher white blood cell (WBC) counts as compared to the corresponding wild-type groups. Total of 45.7% patients achieved complete remission (CR) after the first induction therapy. The CR rate of patients with -ITD or mutation was significantly lower than that in the corresponding wild-type cases (= 0.047, 0.005, respectively). The median overall survival (OS) and disease-free survival (PFS) were 18.0 (95% CI: 10.8-25.2) and 10 (95% CI: 6.7-13.3) months, respectively. -ITD mutations and allogeneic hematopoietic stem cell transplantation (allo-HSCT) were independent prognostic markers for OS in multivariable analysis.
The results suggest a possible association between trisomy 8 and additional mutations that may influence clinical feature and prognosis.
本研究旨在确定以8号染色体三体作为唯一染色体异常的急性髓系白血病（AML）的分子遗传学和临床特征，8号染色体三体是AML中一种反复出现但罕见的染色体异常。
对仅存在8号染色体三体的AML患者进行间期荧光原位杂交、用于基因重排的逆转录定量聚合酶链反应以及下一代测序（NGS）。
共筛选出35例以8号染色体三体作为唯一染色体异常的AML患者。最常发生突变的基因是（37.1%）、（28.6%）、-ITD（28.6%）、（22.9%）、（17.1%）和（14.3%）。与正常核型AML（NK AML）患者（n = 63）相比，仅+8 AML患者在（28.6%对4.8%，P = 0.001）和（14.3%对4.8%，P = 0.039）中表现出更多突变。与相应野生型组相比，存在或突变的仅+8 AML患者（n = 35）白细胞计数显著更低，而-ITD则显示白细胞（WBC）计数更高。首次诱导治疗后，共有45.7%的患者实现完全缓解（CR）。-ITD或突变患者的CR率显著低于相应野生型病例（分别为P = 0.047、0.005）。中位总生存期（OS）和无病生存期（PFS）分别为18.0（95%CI：10.8 - 25.2）个月和10（95%CI：6.7 - 13.3）个月。多变量分析中，-ITD突变和异基因造血干细胞移植（allo - HSCT）是OS的独立预后标志物。
结果表明8号染色体三体与可能影响临床特征和预后的其他突变之间可能存在关联。
