title: Intravascular large B-cell lymphoma: report of three cases and analysis of the mTOR pathway.
abstract: Intravascular large B-cell lymphoma (IVLBCL) is a rare, aggressive and often fatal non-Hodgkin lymphoma characterized by preferential growth of malignant B-cells within the lumina of small vessels. Rituximab plus anthracycline-based chemotherapy is the current standard regimen for IVLBCL, however it has minimal efficacy in relapsed or refractory diseases. Recent clinical trials have shown a significant anti-lymphoma activity of mammalian target of rapamycin (mTOR) inhibitors in relapsed and refractory diffuse large B-cell lymphoma (DLBCL); however, the activation status of the mTOR pathway and the therapeutic potential of mTOR inhibitors in IVLBCL have not yet been studied. Here we described the clinicopathological features of 3 cases of IVLBCL diagnosed at our institutions, and evaluated the activation status of the mTOR signaling in these tumors. Our results showed that the mTOR complex 2 pathway was selectively upregulated in IVLBCL, as evidenced by a predominant nuclear localization of the activated form of mTOR (p-mTOR at Ser2448) with concomitant overexpression of nuclear p-Akt (Ser473) and vascular endothelial growth factor (VEGF)-A in the lymphoma cells. These data suggest that overactivation of mTOR pathway may play a role in lymphomagenesis of IVLBCL and mTORC2 inhibitors may be beneficial in treating IVLBCL.
authors.affiliation: Department of Pathology and Laboratory Medicine, The University of Texas Medical School at Houston, Houston, TX 77030, USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Shen
authors.forename: Xiuzhen
authors.initials: X
authors.lastname: Duan
authors.forename: Wei
authors.initials: W
authors.lastname: Feng
authors.forename: Nghia
authors.initials: N
authors.lastname: Nguyen
authors.forename: Angelo
authors.initials: A
authors.lastname: Lapus
authors.forename: Robert E
authors.initials: RE
authors.lastname: Brown
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
mesh_terms: D000368:Aged; D002469:Cell Separation; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D016403:Lymphoma, Large B-Cell, Diffuse / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D046888:Tissue Array Analysis; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D019043:Vascular Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology
chemical_list: D042461:Vascular Endothelial Growth Factor A; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases