期刊
BLOOD
卷 118, 期 20, 页码 5517-5527出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2011-03-344374
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类别
资金
- Fondo de Investigaciones Sanitarias [PI08/1985, PI05/1623, PI05/2800, PI05/2327, RETIC RD06/0020/0107]
- Asociacion Espanola Contra el Cancer (AECC)
- Ministerio de Ciencia y Tecnologia, Spain [SAF2008-03871]
PIM serine/threonine kinases are over-expressed, translocated, or amplified in multiple B-cell lymphoma types. We have explored the frequency and relevance of PIM expression in different B-cell lymphoma types and investigated whether PIM inhibition could be a rational therapeutic approach. Increased expression of PIM2 was detected in subsets of mantle cell lymphoma, diffuse large B-cell lymphoma (DLBLC), follicular lymphoma, marginal zone lymphoma-mucosa-associated lymphoid tissue type, chronic lymphocytic leukemia, and nodal marginal zone lymphoma cases. Increased PIM2 protein expression was associated with an aggressive clinical course in activated B-like-DLBCL patients. Pharmacologic and genetic inhibition of PIM2 revealed p4E-BP1(Thr37/46) and p4E-BP1(Ser65) as molecular biomarkers characteristic of PIM2 activity and indicated the involvement of PIM2 kinase in regulating mammalian target of rapamycin complex 1. The simultaneous genetic inhibition of all 3 PIM kinases induced changes in apoptosis and cell cycle. In conclusion, we show that PIM2 kinase inhibition is a rational approach in DLBCL treatment, identify appropriate biomarkers for pharmacodynamic studies, and provide a new marker for patient stratification. (Blood. 2011;118(20):5517-5527)
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