| Autor: |
Metzner, A., Precht, C., Fehse, B., Fiedler, W., Stocking, C., Günther, A., Mayr, G. W., Jücker, M. |
| Předmět: |
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| Zdroj: |
Gene Therapy; Apr2009, Vol. 16 Issue 4, p570-573, 4p, 3 Graphs |
| Abstrakt: |
Acute myeloid leukemia (AML) is a malignant disease characterized by deregulated proliferation of immature myeloid cells. Constitutive activation of the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway is frequently detected in approximately 50–70% of AML patients. The gene INPP5D encodes the SH2-containing inositol 5-phosphatase 1 (SHIP1), which is a negative regulator of PI3K/AKT signaling. After lentiviral-mediated gene transfer of INPP5D into CD34+ cells derived from AML patients (n=12) the granulocyte macrophage-colony stimulating factor (GM-CSF)-dependent proliferation was reduced in all samples analyzed (average 86%; range 72–93%). An enzymatically inactive form of SHIP1 (D672A) had no effect. In addition, SHIP1 reduced the autonomous proliferation of CD34+ cells from a patient with a secondary AML who had a very high peripheral blast count (300 × 109 l−1). These data show that SHIP1 can effectively block GM-CSF-dependent and autonomous proliferation of AML cells.Gene Therapy (2009) 16, 570–573; doi:10.1038/gt.2008.184; published online 15 January 2009 [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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