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

Cancer Cell. 2013 Sep 9;24(3):305-17. doi: 10.1016/j.ccr.2013.08.011.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromosome Deletion*
  • Chromosomes, Human, Pair 7
  • Endosomes / metabolism
  • Endosomes / pathology
  • Gene Order
  • Gene Targeting
  • Haploinsufficiency*
  • Hematopoietic Stem Cells / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Leukemia, Experimental
  • Leukemia, Myeloid / diagnosis
  • Leukemia, Myeloid / genetics*
  • Leukemia, Myeloid / mortality
  • Mice
  • Mice, Knockout
  • Moloney murine leukemia virus / pathogenicity
  • Myelodysplastic Syndromes / diagnosis
  • Myelodysplastic Syndromes / genetics*
  • Myelodysplastic Syndromes / mortality
  • Proteins / genetics
  • Proteins / metabolism
  • Retroviridae Infections / genetics
  • Tumor Suppressor Proteins / deficiency
  • Tumor Suppressor Proteins / genetics*
  • Tumor Virus Infections / genetics


  • Intracellular Signaling Peptides and Proteins
  • Proteins
  • SAMD9 protein, human
  • Samd9L protein, mouse
  • Tumor Suppressor Proteins

Supplementary concepts

  • Chromosome 7, monosomy