PIM kinases are progression markers and emerging therapeutic targets in diffuse large B-cell lymphoma
British Journal of Cancer, 06/22/2012
Brault L et al. – This work demonstrates that PIM expression in diffuse large B–cell lymphoma (DLBCL) is associated with activation of the JAK/STAT signalling pathway and with the proliferative activity. The correlation of nuclear PIM1 expression with disease stage and the modest response to small–molecule inhibitors suggests that PIM kinases are progression markers rather than primary therapeutic targets in DLBCL.Methods
- Immunohistochemical staining for PIM kinases and CXCR4 was performed on tissue microarrays from a cohort of 101 DLBCL cases, and the effects of PIM inhibitors on the survival and migration of DLBCL cell lines were determined.
- PIM1 expression significantly correlated with the activation of signal transducer and activator of transcription (STAT) 3 and 5, P-glycoprotein expression, CXCR4-S339 phosphorylation, and cell proliferation.
- Whereas most cases exhibited cytoplasmic or cytoplasmic and nuclear PIM1 and PIM2 expression, 12 cases (10 of the non-germinal centre DLBCL type) expressed PIM1 predominately in the nucleus.
- Interestingly, nuclear expression of PIM1 significantly correlated with disease stage.
- Exposure of DLBCL cell lines to PIM inhibitors modestly impaired cellular proliferation and CXCR4-mediated migration.