人類WWOX基因位在第16對染色體易脆裂的位置上，可轉錄產生「含雙色胺酸功能區氧化還原酶」（亦稱為WWOX，FOR or WOX1)的腫瘤抑制蛋白質。過去的研究指出，WWOX在有壓力的情況下，可能與調節細胞凋亡有關。在人類多種癌症也發現WWOX的表現量有降低的現象。令人驚訝的是，在我們自己建立的全身性剔除Wwox基因的小鼠周邊血液發現，血液細胞數量明顯比野生型及異合型小鼠減少許多，也在缺乏Wwox的小鼠骨髓發現，多種血液前驅細胞的數量都有出現減少的情形，我們更確定了，缺乏Wwox會造成小鼠骨髓中前驅細胞的增殖情形（proliferation）明顯降低。我們也由實驗發現，可能因為缺乏Wwox，進而導致前驅細胞出現內生性的缺陷（intrinsic defect），因此影響正常造血。總結以上的結果，我們證明在正常造血過程中，腫瘤抑制蛋白質WWOX是重要的調節者。
關鍵字：含雙色胺酸功能區氧化還原酶、前驅細胞、正常造血

Human WWOX gene resides in the common fragile site FRA16D on chromosome 16q23.3–24.1 and encodes a candidate tumor suppressor WW domain-containing oxidoreductase (designated WWOX, FOR or WOX1). Previous studies have suggested that WWOX mediates cell apoptosis upon stress responses. Downregulation of WWOX protein expression has been found in many types of human cancers. Strikingly, significantly reduced numbers of hematopoietic cells were examined in the periphery of our generated Wwox-/- mice as compared with wild-type and heterozygous littermates. A pronounced defect in hematopoiesis was observed in Wwox-/- bone marrow. We determined that WWOX deficiency caused significantly reduced cell proliferation in mouse bone marrow. We demonstrated that, compared with wild-type controls, Wwox-/- bone marrow cells have an intrinsic defect during hematopoiesis. Altogether, our findings reveal a novel function of tumor suppressor WWOX as a crucial regulator in hematopoiesis.
Key word: WW domain-containing oxidoreductase, Progenitor cells, Hematopoiesis

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