Fifty years after its discovery, the enigma of monosomy 7 (-7) is eventually unraveling. The key to understanding -7 is "haploinsufficiency" mechanism, through which the function of myeloid tumor-suppressor genes is lost via the deletion/mutation of one allele. In this century, powerful tools such as microarray-CGH and next generation sequencing have enabled the search for tumor-suppressor genes on chromosome 7. Five genes (Samd9, Samd9-like (Samd9L), Ezh2, MLL3, and CUX1) have been identified and their myeloid tumor suppression potential has been verified using mouse models. Mice lacking one Samd9L gene developed MDS at an advanced age, whereas mice children harboring a gain-of-function mutation of Samd9 or Samd9L gene suffer from bone marrow failure, which is frequently followed by childhood MDS with -7, suggesting that these tumor-suppressor genes are the key to understanding not only MDS with -7 but also MDS in general. However, lack of Ezh2 and MLL3, which encode epigenetic regulators, contribute to the promotion of the progression of myeloid tumor cells that harbor abnormalities in the p53 or Ras pathways.
Keywords: Haploinsufficiency; MDS/AML; Samd9/L; −7/del (7q).