Open AccessThe “Never‐Ending” Mouse Models for MLL‐Rearranged Acute Leukemia Are Still Teaching Us
Author(s) -
Ottersbach Katrin,
SanjuanPla Alejandra,
TorresRuíz Raúl,
Bueno Clara,
VelascoHernández Talia,
Menendez Pablo
Publication year - 2018
Publication title -
hemasphere
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.677
H-Index - 11
ISSN - 2572-9241
DOI - 10.1097/hs9.0000000000000057
Subject(s) - leukemia , acute leukemia , fusion gene , chromosomal translocation , biology , myeloid leukemia , cancer research , acute lymphocytic leukemia , gene , immunology , genetics , lymphoblastic leukemia
Themixed lineage leukemia (MLL, also knownasKMT2A) gene is tumor-mutational heterogeneity for secondary driver mutations frequently rearranged in human acute leukemia. Chromosomal rearrangements involving MLL are biologically and molecularly very intriguing because of the unique ability ofMLL to “break and fuse” with more than 135 fusion partners, as recently reported by the 2017 MLL Recombinome Consortium.MLL fusions are commonly associated with poor disease outcome in infant, pediatric, adult, and therapy-induced acute leukemias. The contribution ofMLL fusions to leukemia initiation and evolution, therapy resistance and relapse is still under active investigation. In this issue of HemaSphere, Stavropoulou et al report a novel inducible transgenic mouse model of MLL-ENL-driven mixed lineage acute leukemia which reveals that the cell-of-origin and the fusion gene expression level are both critical determinants for MLL-ENL-driven acute leukemia. Here, we revisit the main advantages and pitfalls for current mouse models for MLL-AF4, MLL-ENL, and MLL-AF9, the commonest MLL translocations found in human acute lymphoid and myeloid acute leukemia. The large variety of mixed lineage leukemia (MLL) gene fusions (affecting 11q23) found in acute leukemia indicates that the MLL gene is a hotspot genomic region for chromosomal translocations. Longitudinal genomic studies reveal large