Ship Inhibition to Direct Hematopoietic Stem Cells and Induce Extramedullary Hematopoiesis

摘要

The present invention concerns inhibition of SHIP expression and/or function in mammalian subjects to direct HSC from the bone marrow to other sites in the body (such as the spleen and/or liver), where they then re-establish blood cell production. The method of the invention can be employed, for example, to rescue or enhance blood cell recovery during bone marrow impairment due to bone-seeking radioisotope exposure, chemotherapy, radiotherapy, infection, or genetic or congenital defects. Preferably, inhibition of SHIP expression and/or function is achieved by administering an effective amount of one or more SHIP inhibitors to the subject. In one embodiment, the subject is suffering from, or at risk of developing, bone marrow failure (such as an aplastic bone marrow failure syndrome). In another embodiment, the subject is suffering from, or at risk of, exposure to a bone-seeking radioisotope. In another embodiment, the subject is suffering from, or at risk of developing, fibrotic or damaged bone marrow due to chemotherapy and/or radiation therapy for cancer.