NUP98-HOXA9 expression in hemopoietic stem cells induces chronic and acute myeloid leukemias in mice
Open Access
- 1 February 2001
- journal article
- research article
- Published by Springer Nature in The EMBO Journal
- Vol. 20 (3) , 350-361
- https://doi.org/10.1093/emboj/20.3.350
Abstract
Here we describe hemopoietic chimeras serving as a mouse model for NUP98–HOXA9‐induced leukemia, which reproduced several of the phenotypes observed in human disease. Mice transplanted with bone marrow cells expressing NUP98–HOXA9 through retroviral transduction acquire a myeloproliferative disease (MPD) and eventually succumb to acute myeloid leukemia (AML). The NUP98 portion of the fusion protein was shown to be responsible for transforming a clinically silent pre‐leukemic phase observed for Hoxa9 into a chronic, stem cell‐derived MPD. The co‐expression of NUP98–HOXA9 and Meis1 accelerated the transformation of MPD to AML, identifying a genetic interaction previously observed for Hoxa9 and Meis1. Our findings demonstrate the presence of overlapping yet distinct molecular mechanisms for MPD versus AML, illustrating the complexity of leukemic transformation.Keywords
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