ORIGINAL ARTICLE New insights to the MLL recombinome of acute leukemias

Chromosomal rearrangements of the human MLL gene areassociated with high-risk pediatric, adult and therapy-asso-ciated acute leukemias. These patients need to be identified,treated appropriately and minimal residual disease wasmonitored by quantitative PCR techniques. Genomic DNA wasisolated from individual acute leukemia patients to identify andcharacterize chromosomal rearrangements involving thehuman MLL gene. A total of 760 MLL-rearranged biopsysamples obtained from 384 pediatric and 376 adult leukemiapatients were characterized at the molecular level. Thedistribution of MLL breakpoints for clinical subtypes (acutelymphoblastic leukemia, acute myeloid leukemia, pediatric andadult) and fused translocation partner genes (TPGs) will bepresented, including novel MLL fusion genes. Combined dataof our study and recently published data revealed 104 differentMLL rearrangements of which 64 TPGs are now characterizedon the molecular level. Nine TPGs seem to be predominantlyinvolved in genetic recombinations of MLL: AFF1/AF4, MLLT3/AF9, MLLT1/ENL, MLLT10/AF10, MLLT4/AF6, ELL, EPS15/AF1P,MLLT6/AF17 and SEPT6, respectively. Moreover, we describefor the first time the genetic network of reciprocal MLL genefusions deriving from complex rearrangements.Leukemia (2009) 23, 1490–1499; doi:10.1038/leu.2009.33;published online 5 March 2009Keywords: MLL; translocations partner genes; acute leukemia;ALL; AML