کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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5939961 | 1573493 | 2006 | 12 صفحه PDF | دانلود رایگان |
Hairy cell leukemia is an uncommon B-cell lymphoproliferative disease of unknown etiology in which tumor cells display characteristic microfilamentous membrane projections. Another striking feature of the disease is its exquisite sensitivity to interferon (IFN)-α. So far, none of the known IFN-α regulatory properties have explained IFN-α responsiveness nor have they taken into account the morphological characteristics of hairy cells. IFN-α profoundly alters cytoskeletal organization of hairy cells and causes reversion of the hairy appearance into a rounded morphology. Because cytoskeletal rearrangements are controlled by the Rho family of GTPases, we investigated the GTPase activation status in hairy cells and their regulation by IFN-α. Using immunolocalization techniques and biochemical assays, we demonstrate that hairy cells display high levels of active Cdc42 and Rac1 and that IFN-α down-regulates these activities. In sharp contrast, RhoA activity was low in hairy cells but was increased by IFN-α treatment. Finally, IFN-α-mediated morphological changes also implicated a p53-induced response. These observations shed light on the mechanism of action of IFN-α in hairy cell leukemia and are of poten-tial relevance for the therapeutical applications of this cytokine.
Journal: The American Journal of Pathology - Volume 168, Issue 2, February 2006, Pages 562-573