Bai Shu-Xiao, Gong Yan-Lei, Zhang Jing-Ren, Wu Chun-Xiao, Zhang Jun, Qiu Hui-Ying, Shen Hong-Jie, Cen Jian-Nong, Chen Su-Ning, Pan Jin-Lan
Jiangsu Institute of Hematology，The First Affiliated Hospital of Soochow University；Key Laboratory of Thrombosis and Hemostasis of Ministry of Health，Suzhou 215006，Jiangsu Province，China.
Jiangsu Institute of Hematology，The First Affiliated Hospital of Soochow University；Key Laboratory of Thrombosis and Hemostasis of Ministry of Health，Suzhou 215006，Jiangsu Province，China,E-mail:
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2020 Jun;28(3):717-723. doi: 10.19746/j.cnki.issn.1009-2137.2020.03.001.
To investigate the clinical significance of AML patients with 11q23/MLL rearrangement, and to evaluate the effect of those mutations on the AML patients.
53 cases involving translocations of chromosome 11q23 were identified by chromosome banding analysis. MLL rearrangements were detected by fluorescence in situ hybridization and/or multiplex nested PCR. The samples were screened for mutations in the candidate genes FLT3-ITD, FLT3-TKD, TET2, N-RAS, ASXLI, EZH2, DNMT3, C-Kit, NPM1, WT1, CEBPA by using genomic DNA-PCR and deep-sequencing.
21/53 MLL-rearranged AML cases showed at least one additional chromosomal aberrations. The most common additional aberration was +8. Gene mutations were observed in 23 cases (43.4%) and most cases showed singal mutation. N-RAS mutation was more frequent (8 cases, 15.1%), followed by WT1 mutation in 4 cases (7.5%), FLT3-ITD mutation in 3 cases, ASXL1 mutation in 2 cases, DNMT3A mutation in 2 cases, EZH2 mutation in 1 case, c-Kit17 mutation in 1 case, FLT3-TKD mutation in 1 case, and FLT3-ITD and TKD mutation coexistent in 1 case. No mutation was detected in CEBPA, NPM1, C-KIT8, TET2. Median OS for gene mutated patients was 8.5 months and 13 months for no mutated patients. Median OS for patients who received hematopoietic stem cell transplantation (HSCT) was 22.5 months and 7.5 months for patients who olny received chemotherapy.
A relatively high mutation frequency is observed in AML patients with 11q23/MLL rearrangements and most cases shows single mutation. The RAS signaling pathway alterations are most common. Gene mutation does not affect the OS of these patients, who show poor prognosis. A significantly higher Hb at initial diagnosis in FLT3 mutated patients is significantly higher than that in FLT3 wild-type cases. Patients who underwent HSCT show a better prognosis than those only received chemotherapy.
探讨11q23/MLL重排的急性髓系白血病（AML）患者的临床意义，并评估这些突变对AML患者的影响。
通过染色体显带分析鉴定出53例涉及11号染色体q23易位的病例。采用荧光原位杂交和/或多重巢式PCR检测MLL重排。利用基因组DNA-PCR和深度测序筛选候选基因FLT3-ITD、FLT3-TKD、TET2、N-RAS、ASXLI、EZH2、DNMT3、C-Kit、NPM1、WT1、CEBPA中的突变。
53例MLL重排的AML病例中，21例显示至少一种额外的染色体畸变。最常见的额外畸变是+8。23例（43.4%）观察到基因突变，大多数病例为单基因突变。N-RAS突变较为常见（8例，15.1%），其次是WT1突变4例（7.5%），FLT3-ITD突变3例，ASXL1突变2例，DNMT3A突变2例，EZH2突变1例，c-Kit17突变1例，FLT3-TKD突变1例，FLT3-ITD和TKD突变共存1例。CEBPA、NPM1、C-KIT8、TET2未检测到突变。基因突变患者的中位总生存期为8.5个月，未突变患者为13个月。接受造血干细胞移植（HSCT）患者的中位总生存期为22.5个月，仅接受化疗的患者为7.5个月。
11q23/MLL重排的AML患者中观察到相对较高的突变频率，大多数病例为单基因突变。RAS信号通路改变最为常见。基因突变不影响这些患者的总生存期，其预后较差。FLT3突变患者初诊时的血红蛋白水平显著高于FLT3野生型病例。接受HSCT的患者比仅接受化疗的患者预后更好。
