Proteomic Profiling Differentiates Lymphoma Patients with and without Concurrent Myeloproliferative Neoplasia

Abstract

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.

Plasma proteomic analysis reveals altered protein abundances in HIV‐infected patients with or without non‐Hodgkin lymphoma

“…Over the past decade, researchers using proteomic approaches have provided information on quantitative and qualitative protein patterns in the blood to identify potential cancer biomarkers. 8,9 However, only a minority of published lymphoma proteomic studies have investigated protein expression in patient blood samples, [10][11][12][13][14][15] particularly samples from patients with AIDS-NHL. Xu et al 16 used surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) to build four models of serum protein fingerprints for identifying potential biomarkers of diffuse large B-cell lymphoma (DLBCL) and distinguishing prognostic markers.…”

Does Double Mean Trouble? Coexistence of Myeloproliferative and Lymphoproliferative Neoplasms: Clinical Observations and Implications

“…Splenic infiltration is often seen in DLBCL, but type of primary splenic DLBCL is rare and studies on its clinicopathological features are limited. Holst J. et al evaluate patients with confirmed dual diagnoses of myeloproliferative neoplasm and lymphoma [15]. They found that the 5-year overall survival rate of the patients with MPN+DLBCL was 19% as compared to 34% for patients in the matched reference cohort with presence only DLBCL.…”

Proteomics identifies apoptotic markers as predictors of histological transformation in patients with follicular lymphoma

“…To identify differentially expressed proteins between the samples, a label-free quantification nano liquid chromatography-tandem MS–based proteomic analysis was performed. 26 , 27 The procedure is described in detail in the supplemental Methods . In brief, proteins from formalin-fixed, paraffin-embedded lymphoma tissues were extracted and proteolytically digested into peptides.…”