Revisiting the biology of infant t(4;11)/MLL-AF4+ B-cell acute lymphoblastic leukemia

Sanjuan-Pla, A. (Alejandra)
Bueno, C. (Clara)
Prieto, C. (Cristina)
Acha, P. (Pamela)
Stam, R.W. (Ronald)
Marschalek, R. (Rolf)
Menéndez, P. (Pablo)

Open link

Publication date

December 2015

DOI

10.1182/blood-2015-09-667378

Publisher

American Society of Hematology

ISSN

0006-4971

Citation count (estimate)

Abstract

Infant B-cell acute lymphoblastic leukemia (B-ALL) accounts for 10% of childhood ALL. The genetic hallmark of most infant B-ALL is chromosomal rearrangements of the mixed-lineage leukemia (MLL) gene. Despite improvement in the clinicalmanagement and survival (∼85-90%) of childhood B-ALL, the outcome of infants withMLL-rearranged (MLL-r) B-ALL remains dismal, with overall survival <35%. Among MLL-r infantB-ALL, t(4;11)1 patients harboring the fusion MLL-AF4 (MA4) display a particularly poor prognosis and a pro-B/mixed phenotype. Studies in monozygotic twins and archived blood spots have provided compelling evidence of a single cell of prenatal origin as the target for MA4 fusion, explaining the brief leukemia latency. Despite its aggressiven...