Haploinsufficiency of SAMD9L, an Endosome Fusion Facilitator, Causes Myeloid Malignancies in Mice Mimicking Human Diseases with Monosomy 7

Akiko Nagamachi, Hirotaka Matsui, Hiroya Asou, Yuko Ozaki, Daisuke Aki, Akinori Kanai, Keiyo Takubo, Toshio Suda, Takuro Nakamura, Linda Wolff, Hiroaki Honda, Toshiya Inaba

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65 Citations (Scopus)

Abstract

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 invivo 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.

Original languageEnglish
Pages (from-to)305-317
Number of pages13
JournalCancer Cell
Volume24
Issue number3
DOIs
Publication statusPublished - 2013 Sep 9

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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    Nagamachi, A., Matsui, H., Asou, H., Ozaki, Y., Aki, D., Kanai, A., Takubo, K., Suda, T., Nakamura, T., Wolff, L., Honda, H., & Inaba, T. (2013). Haploinsufficiency of SAMD9L, an Endosome Fusion Facilitator, Causes Myeloid Malignancies in Mice Mimicking Human Diseases with Monosomy 7. Cancer Cell, 24(3), 305-317. https://doi.org/10.1016/j.ccr.2013.08.011