Lennert lymphoma (LL) is a lymphoepithelioid morphological variant of peripheral T-cell lymphoma—not otherwise specified (PTCL/NOS), clinically characterized by better prognosis if compared with other PTCL/NOS. Although well characterized as far as morphology and phenotype are concerned, very little is known regarding its molecular features. In this study, we investigated the transcriptional profile of this tumor aiming 1) to identify its cellular counterparts; 2) to better define its relation with other PTCLs—and, therefore, its possible position in lymphoma classification; and 3) to define pathogenetic mechanisms, possibly unveiling novel therapeutic targets. To address these issues, we performed gene and microRNA expression profiling on LL and other PTCL/NOS cases; we identified different genes and microRNAs that discriminated LL from other PTCL/NOS. Particularly, LL revealed a molecular signature significantly enriched in helper function and clearly distinguishable from other PTCL/NOS. Furthermore, PI3K/Akt/mTOR pathway emerged as novel potential therapeutic target. In conclusion, based on the already known particular morphological and clinical features, the new molecular findings support the hypothesis that LL might be classified as a separate entity. Preclinical and clinical studies testing the efficacy of PI3K/MTOR inhibitors in this setting are warranted.

This laboratory activity is designed to teach students how to measure forearm muscle blood flow (FBF) to describe the mechanisms of peripheral blood flow thermal regulation in healthy subjects. The cold pressor test (CPT) is the clinical procedure used in the experiment to induce arterial vasoconstriction. Strain-gauge plethysmography is applied on the patient's forearm to noninvasive monitor vasoconstriction effects on local blood perfusion and physiological parameters such as blood pressure (BP) and heart rate (HR). Patients with an altered peripheral vascular resistance (e.g., in hypertension) have different responses to the CPT from healthy subjects. To date, experimental evidence remains unexplained, as we do not know if the BP and HR increase is caused by a decrease in flow rate or an increase in peripheral vascular resistance during the test. To clarify this situation, we have to quantify the parameter we assume is being conditioned by the regulatory physiological intervention, i.e., peripheral vascular resistance. Peripheral vascular resistance quantification can be calculated as the ratio between muscle flow and mean arterial pressure. Students will learn how to apply the instrumental procedure to collect and analyze data before, during, and after the CPT and to describe the physiological responses of the peripheral vascular system to external stressors. They will also learn how to distinguish healthy from pathological responses on the basis of how sympathetic nervous system reactions influence the biomechanics of peripheral vessels.

FXYD3 is a Na/K-ATPase regulator which has been recently associated with different cancers development and progression; consequently, FXYD3 has been proposed in those as a potential therapeutic target. By contrast, no data are available concerning FXYD3 expression in hematological malignancies. In this study we aimed to assess FXYD3 gene expression in a large panel of B-cell derived lymphoid malignancies and to evaluate possible clinic-pathological correlations. Normal B-cell subsets served as control. We found that FXYD3 gene was not significantly modulated in normal B-cells. By contrast, BL, DLBCL, PMBCL, and PCM presented with a significant over-expression of the gene when compared to their cellular counterpart (p<0.0006). Interestingly, tumors characterized by higher FXYD3 expression presented with a significant enrichment in specific cellular functions and pathways, including NFkB pathway, WNT/B-catenin signaling, and MYC network, while FXYD3 levels also turned out to be directly related to PRDM1/BLIMP1. Finally, higher FXYD3 expression was not significantly associated with patients' survival in PCM and DLBCL, though a trend in favour of patients with lower expression was recorded in DLBCL cases. In conclusion, we unveiled FXYD3 gene over-expression in specific non-Hodgkin lymphoma subtypes and PCM, providing evidences of its involvement in their pathobiology. Future studies are needed to define its precise role.

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