| Autor: |
Holst JM; Department of Hematology, Aarhus University Hospital, 8200 Aarhus, Denmark.; Department of Clinical Medicine, Aarhus University, 8000 Aarhus, Denmark., Enemark MB; Department of Hematology, Aarhus University Hospital, 8200 Aarhus, Denmark.; Department of Clinical Medicine, Aarhus University, 8000 Aarhus, Denmark., Pedersen MB; Department of Hematology, Aarhus University Hospital, 8200 Aarhus, Denmark., Lauridsen KL; Department of Pathology, Aarhus University Hospital, 8200 Aarhus, Denmark., Hybel TE; Department of Hematology, Aarhus University Hospital, 8200 Aarhus, Denmark.; Department of Clinical Medicine, Aarhus University, 8000 Aarhus, Denmark., Clausen MR; Department of Hematology, Vejle Hospital, 7100 Vejle, Denmark., Frederiksen H; Department of Hematology, Odense University Hospital, 5000 Odense, Denmark., Møller MB; Department of Pathology, Odense University Hospital, 5000 Odense, Denmark., Nørgaard P; Department of Pathology, Herlev Hospital, 2730 Herlev, Denmark., Plesner TL; Department of Pathology, Rigshospitalet, 2100 Copenhagen, Denmark., Hamilton-Dutoit SJ; Department of Clinical Medicine, Aarhus University, 8000 Aarhus, Denmark.; Department of Pathology, Aarhus University Hospital, 8200 Aarhus, Denmark., d'Amore F; Department of Hematology, Aarhus University Hospital, 8200 Aarhus, Denmark.; Department of Clinical Medicine, Aarhus University, 8000 Aarhus, Denmark., Honoré B; Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark., Ludvigsen M; Department of Hematology, Aarhus University Hospital, 8200 Aarhus, Denmark.; Department of Clinical Medicine, Aarhus University, 8000 Aarhus, Denmark. |
| Abstrakt: |
Myeloproliferative neoplasia (MPN) and lymphoma are regarded as distinct diseases with different pathogeneses. However, patients that are diagnosed with both malignancies occur more frequently in the population than expected. This has led to the hypothesis that the two malignancies may, in some cases, be pathogenetically related. Using a mass spectrometry-based proteomic approach, we show that pre-treatment lymphoma samples from patients with both MPN and lymphoma, either angioimmunoblastic T-cell lymphoma (MPN-AITL) or diffuse large B-cell lymphoma (MPN-DLBCL), show differences in protein expression compared with reference AITL or DLBCL samples from patients without MPN. A distinct clustering of samples from patients with and without MPN was evident for both AITL and DLBCL. Regarding MPN-AITL, a pathway analysis revealed disturbances of cellular respiration as well as oxidative metabolism, and an immunohistochemical evaluation further demonstrated the differential expression of citrate synthase and DNAJA2 protein ( p = 0.007 and p = 0.015). Interestingly, IDH2 protein also showed differential expression in the MPN-AITL patients, which contributes to the growing evidence of this protein's role in both myeloid neoplasia and AITL. In MPN-DLBCL, the disturbed pathways included a significant downregulation of protein synthesis as well as a perturbation of signal transduction. These results imply an underlying disturbance of tumor molecular biology, and in turn an alternative pathogenesis for tumors in these patients with both myeloid and lymphoid malignancies. |
