Biomarkers Of Disease Progression In Non-hodgkin's Lymphoma

PART ? Junctional adhesion molecule-A enhances NODAL signaling and confers lymphoma metastasisThe underlying mechanism of lymphoma metastasis outside lymph nodes remains elusive.Cancer stem-like cells are essential for tumor metastasis.Here we showed that junctional adhesion molecule-A(JAM-A)was overexpressed in diffuse large B-cell lymphoma patients with multiple extranodal lesions.JAM-A overexpression maintained lymphoma cell stemness,led to secretion of matrix metalloproteinases-2(MMP-2)and shedding of MHC class I-related chain A(MICA),thereby reduced cytolytic activity of natural killer(NK)cells and increased aggressiveness of lymphoma cells.Of note,JAM-A selectively activated NODAL signaling and committed lymphoma cell infiltration to mesoendoderm-derived organs.Immunomodulatory agents lenalidomide and chidamide downregulated JAM-A,as well as downstream NODAL and MMP-2 expression,sensitizing lymphoma cells to NK-mediated immunesurveillance and preventing lymphoma metastasis.Collectively,our findings identified JAM-A as a biomarker of stem-cell property and lymphoma immune escape from NK cells,providing clinical rationale of targeting JAM-A/NODAL/MMP-2 axis to counteract extranodal invasion in lymphoma.PART ? The study on detection of long non-coding RNAs and their function in peripheral T-cell lymphomaPeripheral T-cell lymphoma(PTCL)is an important subtype of aggressive lymphoma.PTCL is resistant to chemotherapy and easy to relapse with a rapid progression and poor prognosis.To identify therapeutic target is critical to improve disease outcome.Long non-coding RNA(lnc RNA)plays a pivotal role on biological behavior of normal and tumor cells,including hematological malignancies.The function of most lnc RNAs is remains elusive in PTCL.In this study,combining the data of lnc RNA array and m RNA array,lnc RNA-ST20-AS1 was proven closely related to PTCL.Preliminary biological function and possible mechanism of chemoresistance were performed.