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Impaired differentiation and apoptosis of hematopoietic precursors in a mouse model of myelodysplastic syndrome

Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institute of Health, Bethesda, MD, USA

Correspondence: Peter D. Aplan, Navy 8, Room 5101 8901 Wisconsin Ave, Bethesda MD 20889 USA.E-mail:aplanp{at}mail.nih.gov

Expression of a NUP98-HOXD13 (NHD13) fusion gene, initially identified in a patient with myelodysplastic syndrome, leads to a highly penetrant myelodysplastic syndrome in mice that recapitulates all of the key features of the human disease. Expansion of undifferentiated lineage negative (lin^neg) hematopoietic precursors that express NHD13 was markedly inhibited (30-fold) in vitro. Decreased expansion was accompanied by decreased production of terminally differentiated cells, indicating impaired differentiation of NHD13 precursors. Rather than differentiate, the majority (80%) of NHD13 lin^neg precursors underwent apoptotic cell death when induced to differentiate. These findings demonstrate that NHD13 lin^neg cells provide a tractable in vitro system for studies of myelodysplastic syndrome.

Key words: myelodysplastic syndromes, mouse model, NUP98, HOXD13, apoptosis.