Therapeutic Targeting of the Cyclin D3:CDK4/6 Complex in T Cell Leukemia

详细信息    查看全文

• 作者：Catherine M. Sawai ; Jacquelyn Freund ; Philmo Oh ; Delphine Ndiaye-Lobry ; Jamieson?C. Bretz ; Alex ; ros Strikoudis ; Lali Genesca ; Thomas Trimarchi ; Michelle?A. Kelliher ; Marcus Clark ; Jean Soulier ; Selina Chen-Kiang ; Iannis Aifantis
• 刊名：Cancer Cell
• 出版年：2012
• 出版时间：16 October, 2012
• 年：2012
• 卷：22
• 期：4
• 页码：452-465
• 全文大小：2081 K

文摘

| Figures/TablesFigures/Tables | ReferencesReferences

Summary

D-type cyclins form complexes with cyclin-dependent kinases (CDK4/6) and promote cell cycle progression. Although cyclin D functions appear largely tissue specific, we demonstrate that cyclin D3 has unique functions in lymphocyte development and cannot be replaced by cyclin D2, which is also expressed during blood differentiation. We show that only combined deletion of p27p>Kip1p> and retinoblastoma tumor suppressor (Rb) is sufficient to rescue the development of Ccnd3p>?/?p> thymocytes. Furthermore, we show that a small molecule targeting the kinase function of cyclin D3:CDK4/6 inhibits both cell cycle entry in human T?cell acute lymphoblastic leukemia (T-ALL) and disease progression in animal models of T-ALL. These studies identify unique functions for cyclin D3:CDK4/6 complexes and suggest potential therapeutic protocols for this devastating blood tumor.