title: [Clinical and experimental studies of childhood acute myeloid leukemia with 11q23/MLL rearrangements].
abstract: OBJECTIVE
  To explore clinical and experimental features of 28 cases of childhood acute myeloid leukemia (AML) with 11q23/MLL gene rearrangements.
  
  
  METHODS
  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).
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Hematology & Cancer Biology Unit, Children's Hospital of Soochow University, Suzhou, Jiangsu 215003, P R China. yaxianghe@163.com
authors.forename: Ya-xiang
authors.initials: YX
authors.lastname: He
authors.forename: Yong-quan
authors.initials: YQ
authors.lastname: Xue
authors.forename: Hong-ying
authors.initials: HY
authors.lastname: Wang
authors.forename: Xue-jun
authors.initials: XJ
authors.lastname: Shao
authors.forename: Jin-lan
authors.initials: JL
authors.lastname: Pan
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
authors.forename: Nai-chao
authors.initials: NC
authors.lastname: Yang
authors.forename: Zheng-hua
authors.initials: ZH
authors.lastname: Ji
authors.forename: Yi-ping
authors.initials: YP
authors.lastname: Huang
authors.forename: Shao-yan
authors.initials: SY
authors.lastname: Hu
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002880:Chromosomes, Human, Pair 11; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007621:Karyotyping; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D008297:Male; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D012074:Remission Induction; D014178:Translocation, Genetic; D016896:Treatment Outcome
chemical_list: D051788:Myeloid-Lymphoid Leukemia Protein