Abstract
Simple SummaryPatients are diagnosed with myeloproliferative neoplasia (MPN) and lymphoma more frequently in the population than expected, which has led to the hypothesis that the two malignancies may, in some cases, be pathogenetically related. In this study, lymphoma patients with and without MPN show subtle but important differences in the protein expression that enables the clustering of the lymphomas, thus indicating the differences at the molecular level between the lymphoma malignancies with and without MPN, and strengthening the hypothesis that the lymphoma and MPN may be biologically related.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.
Highlights
Myeloproliferative neoplasia (MPN) and lymphoma are traditionally thought to develop by different pathogenetic mechanisms, leading to the occurrence of distinct diseases [1,2]
Lymphomas are malignancies that are derived from mature lymphocytes whereas MPN are clonal hematopoietic stem cell disorders that are characterized by the malignant proliferation of one or more of the myeloid-derived cell lineages [1,2]
Our findings suggested that further investigations comparing the tumor biology of lymphomas that develop in patients both with and without concomitant MPN might be of interest
Summary
Myeloproliferative neoplasia (MPN) and lymphoma are traditionally thought to develop by different pathogenetic mechanisms, leading to the occurrence of distinct diseases [1,2]. Patients that are diagnosed with both malignancies, i.e., MPN and lymphoma, occur at higher frequencies than expected compared with the background population [3,4,5]. Such observations have fostered the hypothesis that these two hematological malignancies, in some cases, may share molecular alterations representing a possible pathogenetic relationship. MPN encompasses the entities essential thrombocythemia (ET), polycythemia vera (PV), primary myelofibrosis (PMF), chronic myeloid leukemia, and MPN-unclassifiable (MPN-U) [2,6] In spite of their distinct clinicopathological features, MPN can be viewed as a disease spectrum with shared genetic and clinical aberrations [7]. Well-known recurrent alterations include mutations involving the JAK2, CALR or MPL genes, which are found in approximately 90% of patients with
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
