Analysis of t(9;11) chromosomal breakpoint sequences in childhood acute leukemia: Almost identical MLL breakpoints in therapy‐related AML after treatment without etoposides

• DOI: 10.1002/gcc.10167
• Publication Date: 2003-03-18T22:54:05Z
• Authors: Thorsten Langer; Markus Metzler; Dirk Reinhardt; Susanne Viehmann; Arndt Borkhardt; Martin Reichel; Martin Stanulla; Martin Schrappe; Ursula Creutzig; Jörg Ritter; Thomas Leis; Ulla Jacobs; Jochen Harbott; Jörn D. Beck; Wolfgang Rascher; Reinald Repp
• Keywords: Breakpoint; breakpoint cluster region

Abstract The translocation t(9;11)(p22;q23) is a recurring chromosomal abnormality in acute myeloid leukemia (AML) fusing two genes designated as MLL and AF9. Within MLL, almost all rearrangements cluster an 8.3‐kb restricted region fuse 5′ portions of to variety heterologous various 11q23 translocations. AF9 one the most common fusion partners MLL. It spans more than 100 kb, breakpoint regions (BCRs) have been identified telomeric intron 4 (BCR1) within introns 7 8 (BCR2). We investigated 11 children's bone marrow or peripheral blood samples (3 AML, 5 t‐AML, 2 ALL, 1 ALL relapse) cell lines (THP‐1 Mono‐Mac‐6) with cytogenetically diagnosed translocations t(9;11). By use optimized multiplex nested long‐range PCR assay, breakpoint‐spanning DNA fragment from each sample was amplified directly sequenced. In four patients lines, breakpoints were located BCR1 BCR2, respectively. However, five found outside previously described BCRs centromeric even 3 case. All secondary who had not received etoposides during treatment primary malignant disease, revealed identical very close breakage hot spot inducible by topoisomerase II inhibitors apoptotic triggers vitro. Sequence patterns around indicated involvement “damage‐repair mechanism” development t(9;11) similar t(4;11) infants' leukemia. © 2003 Wiley‐Liss, Inc.