Biological characterization of <italic>MLL-NRIP3</italic> fusion gene induced leukemia

Abstract

Leukemia, originating from hematopoietic stem or progenitor cells, is a malignant proliferative tumor which seriously endangers human health and survival. It is the most common childhood malignancy with an increasing proportion of malignancy in adults. Acute myeloid leukemia (AML) involving MLL (mixed lineage leukemia, MLL-r ) translocation is recognized as an aggressive form of hematopoietic malignancies that exhibit a blockade of differentiation, disruption of genetic and epigenetic regulation, and poor prognosis. Although MLL-NRIP3 fusion gene has been reported recently in establishing leukemia mouse model and its effect on leukemia progression in MLL-r mouse model has also been demonstrated, its leukemia biological characteristics were still not well characterized. Here we investigate the basic biological phenotypes of two MLL-r mouse models ( MLL-AF9 and MLL-NRIP3 ), including: the survival of recipient mice transplanted with leukemia cells; the migration and adhesion abilities of leukocyte cells; the number and the function of leukemia stem cells (LSCs), cell cycle and cell apoptosis, and investigate whether the surface markers of LSCs reported previously are equally applicable to MLL-NRIP3 leukemia cells. The results showed that the survival time of MLL-NRIP3 recipient mice was longer than that of MLL-AF9 . The migration ability of MLL-NRIP3 leukemia cells was less capable than MLL-AF9 , while adhesion was stronger than MLL-AF9 cells. Cell cycle and cell apoptosis of two MLL-r leukemia cells basically had no difference. C olony - forming unit assay and limiting dilution assay both revealed that MLL-AF9 leukemia had a higher number of functional LSCs than MLL-NRIP3 . In summary, MLL-NRIP3 induced leukemia is a low LSCs-enriched MLL-r .