Pathophysiology and molecular aspects of diffuse large B-cell lymphoma

Abstract

Diffuse large B-Cell lymphoma is the most common subtype of non-Hodgkin lymphoma in the West. In Brazil, it is the fifth cause of cancer, with more than 55,000 cases and 26,000 deaths per year. At Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - HCFMUSP, diffuse large B-Cell lymphoma represents 49.7% of all non-Hodgkin lymphoma cases. Initially, the classification of non-Hodgkin lymphoma was based on morphology, but advances in immunology and molecular medicine allowed the introduction of a biological classification for these diseases. As for other cancers, non-Hodgkin lymphoma involves patterns of multifactorial pathogenesis with environmental factors, as well as genetic, occupational and dietary factors, contributing to its development. Multiple lesions involving molecular pathways of B-cell proliferation and differentiation may result in the activation of oncogenes such as the BCL2, BCL6, and MYC genes and the inactivation of tumor suppressor genes such as p53 and INK4, as well as other important transcription factors such as OCT-1 and OCT-2. A dramatic improvement in survival was seen after the recent introduction of the anti-CD20 monoclonal antibody. The association of this antibody to the cyclophosphamide, hydroxydaunorubicin, oncovin and prednisolone (CHOP) regimen has increased overall survival of diffuse large B-Cell lymphoma and follicular lymphoma patients by 20%. However, 50% of all diffuse large B-Cell lymphoma patients remain incurable, creating a demand for more research with new advances in treatment. Thus, it is important to know and understand the key factors and molecular pathways involved in the pathogenesis of diffuse large B-Cell lymphoma.

Cutaneous Double-Hit B-Cell Lymphoma

“…15 This classification scheme transcends to primary cutaneous diffuse large cell B-cell lymphomas of the skin. The site, cell of origin, and cytogenetic profile define important parameters influencing prognosis.…”

Reactive oxygen species mediate oridonin-induced apoptosis through DNA damage response and activation of JNK pathway in diffuse large B cell lymphoma

“…Despite improvements in the overall survival of patients with DLBCL treated with routine addition of rituximab (an anti-CD20 monoclonal antibody) therapy, one-third of patients have a disease that is either refractory to initial therapy or relapses after standard therapy, which eventually refers to poor disease outcomes for the patients [2]. 50% of all diffuse large B-Cell lymphoma patients remain incurable, creating a demand for more research with new advances in treatment [3]. There has been increasing evidence that diverse mechanisms resulting in the deregulation of cell cycle and apoptotic pathways are involved in the pathogenesis of DLBCL [4].Defects in apoptosis contribute to tumor progression and drug resistance, which are linked to failure of chemotherapy [5].…”

Giant solitary primary intracranial lymphoma masquerading as meningioma: a case and review of literature

“…Diffuse large B cell lymphoma (DLBCL) is the most prevalent subtype, constituting about 90-95% of the total number of lymphomas. DLBCL are often observed in immunocompromised patients as assertive intraparenchymal lesions [ 2 - 4 ]. Also, NHL comprises of about 2-7% of primary intracranial tumors [ 1 , 2 , 5 ].…”

“…Also, NHL comprises of about 2-7% of primary intracranial tumors [ 1 , 2 , 5 ]. PCNSL mostly arises from the brain parenchyma although spinal cord, eyeball and cranial nerve have been reported in literature [ 4 , 6 , 7 ]. The brain parenchyma lymphomas are associated with diffuse edema as well as increased intracranial pressure (ICP), mental and personality changes [ 4 , 8 ].…”

“…PCNSL mostly arises from the brain parenchyma although spinal cord, eyeball and cranial nerve have been reported in literature [ 4 , 6 , 7 ]. The brain parenchyma lymphomas are associated with diffuse edema as well as increased intracranial pressure (ICP), mental and personality changes [ 4 , 8 ]. Computer tomographic scan (CT-Scan) and magnetic resonance imaging (MRI) usually show a single or multiple extra-axial dura centered lesions, which enhance diffusely on contrast enhancing studies [ 7 ].…”