A Complex T(10;11) MLL-AF10 Translocation with Duplication of the Rearranged Chromosome 10 in a Patient Affected with An AML M2
Authors: Bernasconi Paolo , Dambruoso Irene , Boni Marina , Zappatore Rita , Cavigliano Paola Maria , Caresana Marilena , Astori Cesare , Castagnola Carlo , Lazzarino Mario 
Published: April 2020

Abstract
The t(10,11)(p12;q23) translocation is a recurrent and rare chromosomal abnormality in AML, especially associated with the M5 cytotype. An heterogeneity in 10p breakpoints has been revealed by cytogenetic studies even if molecular analysis have demonstrated that the AF10 gene is constantly involved in this translocation. Up to now, two types of chimeric transcripts the MLL-AF10 in the t(10;11)(p12;q23) and the CALM-AF10 in the t(10;11) (p13;q14) have been isolated. In 1998 the Abl-interactor 1 (ABI1) gene was identified as a new MLL partner in the t(10;11) translocation. In addition, it was demonstrated that this chromosomal rearrangement is significantly associated with complex translocations including invins(10;11) and inv(11)t(10;11). However, a duplication of the chromosome 10 derivative has never been reported. Herein we describe an additional female patient with a complex t(10;11) rearrangement and a M2 AML. She was forty-seven years old. Her blood count was the following: haemoglobin 9,4g/dl, WBC 34,2×109/l (blast cells 88%), Plts 7.0×109/l. Induction chemotherapy determined a complete remission (CR) which lasted six months. A second CR was achieved and subsequently the patient was submitted to an allogeneic bone marrow transplant. Now she is alive and well twelve months posttransplant. On clinical diagnosis cytogenetic studies on bone marrow cells revealed the following karyotype: 46,XX/46,XX,t(10;11)(p14;q23), −10, +der(10)t(10;11). FISH studies were performed with the following probes: LSI MLL and LSI ATM from Vysis, Whole Chromosome Painting (WCP) 11 and Arm Chromosome Painting (ACP) 10p from Q-Biogene. In order to better define the rearranged chromosomal region the RP11-47P2 (mapping at 10p15.1), the RP11-79F9 (corresponding to 10p14), the RP11-13C4 and the RP11-36M5 (covering the PLZF3 gene at 11q23.2), the RP11-19S45 and the RP11-48M23 (covering the ABI1 gene at 10p12.1), the RP11-46N13 and the RP-140P12 (covering the AF10 gene at 10p12.31) BAC probes were applied. Other genes investigated with the same approach were the SLC39A12 at 10p12.33, the PLXDC2 at 10p12.33-p12.32, the ARMETL1 at 10p13 and the PIP5K2A at 10p12.31. The WCP 11 and the ACP 10p probes confirmed the t(10;11) translocation, the loss of the normal chromosome 10 and the duplication of der(10)t(10;11). When analysing chromosome 11, the ATM and the PLZF3 probes were in a normal position so neither gene was rearranged. Instead, both the signals (red and green) corresponding to MLL were translocated to chromosome 10 and split by an additional rearrangement. So, we hypothesized that the t(10;11) translocation occurred first and was followed by an additional defect. This possibility was confirmed by the presence of chromosome 10 material inserted between the two MLL signals, an event which was interpreted as either an inversion or an insertion. When analysing chromosome 10, the RP11-79F9 green probe remained in the correct position, whereas the RP11-47P2 red probe was translocated to chromosome 11. Thus, in the initial t(10;11) the breakpoints on chromosome 10 fell within the region delimited by these two BAC probes. Based on the fact that either the AF10 or the ABI1 gene, located at 10p12, are MLL partners in the usually complex t(10;11) translocations we checked whether these genes were involved in the secondary rearrangement on chromosome 10. FISH studies excluded any ABI1 rearrangement. Instead, they demonstrated that the RP11-46N13 (green) and RP-140P12 (red) BAC probes, covering the AF10 gene, were still located on 10p but separated by the chromosomal material belonging to chromosome 11 carrying the two MLL signals at its extremities. Since the two signal corresponding to the AF10 gene were located in the same position of MLL split signals a AF10/MLL translocation had occurred in our patient, who is the first one up to now reported to present a duplication of the rearranged chromosome 10.