Recurrent genetic fusions redefine <i>MLL </i>germ line acute lymphoblastic leukemia in infants
Grazia Fazio, Michela Bardini, Paola De Lorenzo, Andrea Grioni, Manuel Quadri, Lucia Pedace, L Corral Abascal, Sonia Palamini, Chiara Palmi, Barbara Buldini, Luciana Vinti, Rosanna Parasole, Elena Barisone, Marco Zecca, Claudio Favre, Franco Locatelli, Valentino Conter, Carmelo Rizzari, Maria Grazia Valsecchi, Andrea Biondi, Giovanni Cazzaniga
Abstract
B-cell precursor (BCP) acute lymphoblastic leukemia (BCP-ALL) in infants (ie, children age <1 year) is a rare disease traditionally subdivided into MLL-rearranged (alias KMT2A; MLL-R) and MLL germ line (MLL-G) subtypes. MLL gene rearrangements occur in ∼75% of infants with BCP-ALL1-3 and are typically associated with a mixed-lineage phenotype.4 MLL rearrangements originate prenatally in utero5 and play a role in transcription factor dysregulation.6 MLL-R BCP-ALL in infants is associated with dismal outcomes.1-3 Infants with MLL-G ALL treated with intensive therapies in the Interfant-06 protocol may have a relatively favorable prognosis, with a 6-year event-free survival (EFS) rate of 73.9%,2 slightly inferior to that observed in older children with BCP-ALL.1,2 Of interest, a recent study from the Japanese Pediatric Leukemia/Lymphoma Study Group MLL-10 trial reported more favorable outcomes in infants