1.Department of Pediatric Oncology/Hematology, Erasmus MC-Sophia Childrens Hospital, Rotterdam, The Netherlands (EAC, CMZ, MMHE); Acute Myeloid Leukemia-Berlin-Frankfurt-Munster Study Group, Department of Pediatric Hematology, Oncology, Justus-Liebig-University, Giessen, Germany (JH); Department of Pathology (Room 4023A), St. Jude Childrens Research Hospital, 332 North Lauderdale Street, Memphis, Tennessee 38105-2794, USA (SCR)2.Department of Pediatric Oncology/Hematology, Erasmus MC-Sophia Children s Hospital, Rotterdam, The Netherlands (EAC, CMZ, MMHE); Acute Myeloid Leukemia-Berlin-Frankfurt-Munster Study Group, Department of Pediatric Hematology, Oncology, Justus-Liebig-University, Giessen, Germany (JH); Department of Pathology (Room 4023A), St. Jude Children s Research Hospital, 332 North Lauderdale Street, Memphis, Tennessee 38105-2794, USA (SCR)
t(10;11)(p12;q23)- The t(10;11)(p12;q23) is the second most frequent 11q23/MLL abnormality in pediatric AML, accounting for approximately 13% of all cases of 11q23/MLL rearranged pediatric AML. However, this percentage is underestimated, because in many instances the generation of the fusion gene is cryptic or complex (see below). It is difficult to accurately establish the breakpoints of 10p in many translocations involving 10p and 11q23.- The fusion gene resulting from this translocation involves MLL and AF10 (MLLT10).- To generate an MLL-AF10 fusion, the translocation of chromosome 10 and chromosome 11 has to include at least one inversion. Most t(10;11)(p12;q23) cases are identified by conventional karyotyping, but structural aberrations can be very complex. These aberrations include insertions of 11q material onto the 10p arm and vice versa, some of which are also cryptic. In some instances, FISH using the subtelomeric probes for 10p and 11q can clarify the nature of the abnormality. RT-PCR is also a very useful method to detect the MLL-AF10 fusion transcript.- In approximately 50% of the t(10;11)(p12;q23) cases, additional cytogenetic aberrations have been detected by conventional karyotyping. The most frequently recurring additional aberration is trisomy 8 (~7%); diverse structural additional aberrations have been detected (36%) and can affect other chromosomes.- A 5-year EFS of 31% and a 5-year OS of 45% were reported in a large international retrospective study.
t(10;11)(p11.2;q23)- The t(10;11)(p11.2;q23) is a rare 11q23/MLL abnormality mainly found in young children with AML. However, in the large retrospective study, 3 of 12 (25%) patients were older than 2 years.- The fusion gene resulting from this translocation involves MLL and ABI1.- In approximately 58% of t(10;11)(p11.2;q23) cases, additional cytogenetic aberrations have been detected by conventional karyotyping, all cases displaying at least one additional structural aberration.- A 5-year EFS of 17% and a 5-year OS of 27% were reported in a large international retrospective study.
t(6;11)(q27;q23)- The t(6;11)(q27;q23) occurs in approximately 5% of all pediatric patients with 11q23/MLL rearranged AML. However, this incidence is underestimated as the DNA exchanged in this translocation is very subtle and may go undetected or be misclassified as a del(11)(q23).- The fusion gene resulting from this translocation involves MLL and AF6 (MLLT4). RT-PCR is also a very useful method to identify the MLL-AF6 fusion transcript.- In approximately 46% of t(6;11)(q27;q23) cases, additional cytogenetic aberrations have been detected by conventional karyotyping. The most frequent recurring additional aberrations are trisomy 8 and trisomy 21 (~17% each) and additional structural aberrations (~26%).- A 5-year EFS of 11% and a 5-year OS of 22% have been reported in a large international retrospective study; t(6;11)(q27;q23) thus represents the subgroup with the worst outcome in pediatric 11q23/MLL rearranged AML, but the reason for the very poor survival rate is unknown.
t(11;19)(q23;p13)- Translocations of chromosome 11q23 with chromosome 19p13 occur in approximately 12% of pediatric patients with 11q23/MLL rearranged AML. Two common translocation partners are present on 19p13: ELL on 19p13.1 and ENL (MLLT1) on 19p13.3. In approximately 33% of pediatric AML cases, resolution of the karyotype can be insufficient to define the sub-band with certainty, and for this publication these patients are grouped as t(11;19)(q23;p13).- A 5-year EFS for patients with a t(11;19)(q23;p13), t(11;19)(q23;p13.1), and t(11;19)(q23;p13.3) of 49%, 46% and 46% respectively, and a 5-year OS of 49%, 61% and 47%, respectively, have been reported in a large international retrospective study.
t(1;11)(q21;q23)- The t(1;11)(q21;q23) occurs in approximately 3% of all pediatric patients with 11q23/MLL rearranged AML. - The fusion gene resulting from this translocation involves MLL and AF1q (MLLT11).- In approximately 25% of t(1;11)(q21;q23) cases, additional cytogenetic aberrations have been detected by conventional karyotyping, the most frequent being trisomy 6 (13%).- A 5-year EFS of 92% and a 5-year OS of 100% have been reported in a large international retrospective study; t(1;11)(q21;q23) thus represents the subgroup with the best outcome in pediatric 11q23/MLL rearranged AML.
Eva A Coenen ; Jochen Harbott ; Christian Michel Zwaan ; Susana C Raimondi ; Mary M van den Heuvel-Eibrink
11q23 rearrangements (KMT2A) in de novo childhood acute myeloid leukemia
Atlas Genet Cytogenet Oncol Haematol. 2012-03-01
Online version: http://atlasgeneticsoncology.org/haematological/1615/11q23-rearrangements-(kmt2a)-in-de-novo-childhood-acute-myeloid-leukemia