He Ya-xiang, Xue Yong-quan, Wang Hong-ying, Shao Xue-jun, Pan Jin-lan, Xu Jun, Yang Nai-chao, Ji Zheng-hua, Huang Yi-ping, Hu Shao-yan
Hematology & Cancer Biology Unit, Children's Hospital of Soochow University, Suzhou, Jiangsu 215003, P R China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2012 Dec;29(6):677-82. doi: 10.3760/cma.j.issn.1003-9406.2012.06.011.
To explore clinical and experimental features of 28 cases of childhood acute myeloid leukemia (AML) with 11q23/MLL gene rearrangements.
Karyotypes of 234 cases of de novo childhood AML were analyzed using short-term culture of bone marrow cells and R-banding. The fusion transcripts involving MLL gene and partial tandem duplication of MLL (MLL-PTD) were detected by multiple reverse transcription polymerase chain reaction (RT-PCR) assay. Two cases with 11q23 translocation by karyotypic analysis but with negative result of multiple RT-PCR were studied with MLL-dual-color fluorescence in situ hybridization (D-FISH).
R-banding karyotypic analysis has revealed 20 cases with 11q23 translocation (14 cases with M5, 4 cases with M4, 2 cases with M2), including 12 cases with t(9;11)(p22;q23), 3 cases with t(1;11)(q21;q23), 2 cases with t(6;11)(q27;q23), 1 case with t(11;19)(q23;p13), 1 with t(5;11)(q31;q23), and 1 with t(X;11)(q24;q23). Eighteen cases with 11q23 translocation having fusion transcripts involving MLL genes were confirmed with multiple RT-PCR; 2 cases showed negative results, but they were confirmed to have MLL rearrangements by D-FISH. MLL-PTD was also detected in 8 cases (4 cases M5, 2 cases M4, M2 and M6, one case each) from the other childhood AML cases. The total incidence of 11q23/MLL gene rearrangements was 11.97% (28/234), and most of patients(85.7%, 24/28) were M4/M5. The complete remission (CR) rate after treatment for the 28 cases with MLL rearrangements was 53.8%, the difference was significant by statistics (P< 0.05) compared with 90.5% for the control group (M4/M5 childhood AML with other karyotypic abnormalities or normal karyotype). Of them, 2 cases receiving intensive chemotherapy survived for 81 and 66 months, respectively, 4 cases receiving allogeneic stem cell transplantation survived for 21, 20, 16 and 11 months, respectively, and are still alive with CR. The medium survival (MS) time for 28 cases with 11q23/MLL rearrangements was 11 months, whereas the MS for control group was 15 months. The difference was not statistically significant(P> 0.05).
The 11q23/MLL rearrangements is highly correlated with the occurrence of monocytic leukemia (M4 and M5). The 11q23 translocation and MLL-PTD are mutually exclusive, though both are indicative of poor prognosis. Intensive chemotherapy and allogeneic stem cell transplantation may ameliorate the clinical outcome. Multiple RT-PCR combined with karyotypic analysis and D-FISH are useful for screening the 11q23/MLL rearrangements in childhood AML.
探讨28例伴有11q23/MLL基因重排的儿童急性髓系白血病（AML）的临床及实验特征。
采用骨髓细胞短期培养及R显带技术分析234例初发儿童AML的核型。应用多重逆转录聚合酶链反应（RT-PCR）检测涉及MLL基因的融合转录本及MLL基因部分串联重复（MLL-PTD）。对2例经核型分析显示11q23易位但多重RT-PCR结果阴性的病例进行MLL双色荧光原位杂交（D-FISH）研究。
R显带核型分析发现20例有11q23易位（M5型14例，M4型4例，M2型2例），包括t(9;11)(p22;q23) 12例，t(1;11)(q21;q23) 3例，t(6;11)(q27;q23) 2例，t(11;19)(q23;p13) 1例，t(5;11)(q31;q23) 1例，t(X;11)(q24;q23) 1例。18例有11q23易位且涉及MLL基因融合转录本的病例经多重RT-PCR证实；2例结果阴性，但经D-FISH证实有MLL重排。在其他儿童AML病例中，还检测到8例MLL-PTD（M5型4例，M4型、M2型和M6型各2例，各1例）。11q23/MLL基因重排的总发生率为11.97%（28/234），大多数患者（85.7%，24/28）为M4/M5型。28例MLL重排患者治疗后的完全缓解（CR）率为53.8%，与对照组（伴有其他核型异常或核型正常的儿童M4/M5型AML）的90.5%相比，差异有统计学意义（P<0.05）。其中，2例接受强化化疗的患者分别存活81个月和66个月，4例接受异基因干细胞移植的患者分别存活21、20、16和11个月，且均处于CR状态存活。28例11q23/MLL重排患者的中位生存（MS）时间为11个月，而对照组为15个月。差异无统计学意义（P>0.05）。
11q23/MLL重排与单核细胞白血病（M4和M5）的发生高度相关。11q23易位与MLL-PTD相互排斥，二者均提示预后不良。强化化疗和异基因干细胞移植可能改善临床结局。多重RT-PCR联合核型分析及D-FISH有助于筛查儿童AML中的11q23/MLL重排。
