[PDF][PDF] Haploinsufficiency of SAMD9L, an endosome fusion facilitator, causes myeloid malignancies in mice mimicking human diseases with monosomy 7

A Nagamachi, H Matsui, H Asou, Y Ozaki, D Aki… - Cancer cell, 2013 - cell.com
A Nagamachi, H Matsui, H Asou, Y Ozaki, D Aki, A Kanai, K Takubo, T Suda, T Nakamura
Cancer cell, 2013cell.com
Monosomy 7 and interstitial deletion of 7q (− 7/7q−) are well-recognized nonrandom
chromosomal abnormalities frequently found among patients with myelodysplastic
syndromes (MDSs) and myeloid leukemias. We previously identified candidate myeloid
tumor suppressor genes (SAMD9, SAMD9-like= SAMD9L, and Miki) in the 7q21. 3 subband.
We established SAMD9L-deficient mice and found that SAMD9L+/− mice as well as
SAMD9L−/− mice develop myeloid diseases resembling human diseases associated with …
Summary
Monosomy 7 and interstitial deletion of 7q (−7/7q−) are well-recognized nonrandom chromosomal abnormalities frequently found among patients with myelodysplastic syndromes (MDSs) and myeloid leukemias. We previously identified candidate myeloid tumor suppressor genes (SAMD9, SAMD9-like = SAMD9L, and Miki) in the 7q21.3 subband. We established SAMD9L-deficient mice and found that SAMD9L+/− mice as well as SAMD9L−/− mice develop myeloid diseases resembling human diseases associated with −7/7q−. SAMD9L-deficient hematopoietic stem cells showed enhanced colony formation potential and in vivo reconstitution ability. SAMD9L localizes in early endosomes. SAMD9L-deficient cells showed delays in homotypic endosome fusion, resulting in persistence of ligand-bound cytokine receptors. These findings suggest that haploinsufficiency of SAMD9L and/or SAMD9 gene(s) contributes to myeloid transformation.
cell.com