Introduction: Primary gastrointestinal non-Hodgkin lymphoma (PGIL) is a rare hematopoietic malignancy with limited data to guide management. Methods: We analyzed the clinical characteristics and survival of 219 newly diagnosed PGIL patients. Results: Our single-center data showed that the incidence rate of primary gastric lymphoma (PGL) was higher than that of primary intestine lymphoma (PIL). Most PGIL was B-cell originated and DLBCL was the most common pathological type both in PGL and PIL group. Univariate and multivariate analysis showed that IPI score and pathology were independent prognostic factors. The overall survival (OS) and progression-free survival (PFS) of patients with MYC rearrangement were much shorter compared to patients without MYC rearrangement indicating that MYC translocation was related to decreased survival. Neither OS nor PFS differed between patients who received chemotherapy with or without surgery. However, patients who received surgery alone had a poor prognosis. Conclusion: Chemotherapy is the front-line treatment for PGIL while surgery was conducted to relieve tumor-related complications or make diagnosis. MYC rearrangement predicted poor prognosis of PGIL patients.

The development of acute lymphoblastic leuakemia (ALL) is partly attributed to the effects of bone marrow (BM) microenvironment, especially mesenchymal stromal cells (MSCs), which interact bilaterally with leukaemia cells, leading to ALL progression. In order to find MSCs-based microenvironment targeted therapeutic strategies, Notch1-induced T-cell ALL (T-ALL) mice models were used and dynamic alterations of BM-MSCs with increased cell viability during T-ALL development was observed. In T-ALL mice derived stroma-based condition, leukaemia cells showed significantly elevated growth capacity indicating that MSCs participated in leukaemic niche formation. RNA sequence results revealed that T-ALL derived MSCs secreted fibroblast growth factor 2 (FGF2), which combined with fibroblast growth factor receptor 2 (FGFR2) on leukaemia cells, resulting in activation of PI3K/AKT/mTOR signalling pathway in leukaemia cells. In vitro blocking the interaction between FGF2 and FGFR2 with BGJ398 (infigratinib), a FGFR1-3 kinase inhibitor, or knockdown FGF2 in MSCs by interference caused deactivation of PI3K/AKT/mTOR pathway and dysregulations of genes associated with cell cycle and apoptosis in ALL cells, leading to decrease of leukaemia cells. In mouse model received BGJ398, overall survival was extended and dissemination of leukaemia cells in BM, spleen, liver and peripheral blood was decreased. After subcutaneous injection of primary human T-ALL cells with MSCs, tumour growth was suppressed when FGF2/FGFR2 was interrupted. Thus, inhibition of FGF2/FGFR2 interaction appears to be a valid strategy to overcome BM-MSCs mediated progression of T-ALL, and BGJ398 could indeed improve outcomes in T-ALL, which provide theoretical basis of BGJ398 as a BM microenvironment based therapeutic strategy to control disease progression.