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Challenges and Opportunities for High-grade B-Cell Lymphoma With MYC and BCL2 and/or BCL6 Rearrangement (Double-hit Lymphoma). 2019

Dongfeng Zeng, and Aakash Desai, and Fangfang Yan, and Tiejun Gong, and Haige Ye, and Makhdum Ahmed, and Krystle Nomie, and Jorge Romaguera, and Richard Champlin, and Shaoying Li, and Michael Wang
Departments of Lymphoma and Myeloma.

The most common subtype of non-Hodgkin lymphoma, diffuse large B-cell lymphoma, is cured in approximately two thirds of patients after initial therapy. The remaining one-third of patients who suffer relapse or become refractory have very poor survival outcomes despite salvage chemotherapy with or without stem cell transplantation. A considerable proportion of relapsed or refractory large B cells belong to the WHO subtype known as high-grade B-cell lymphoma with rearrangement of MYC and BCL2 and/or BCL6, also known as double-hit lymphoma (DHL). Most DHL patients present with Ann Arbor's stage III/IV, a comparatively higher rate of extranodal involvement including bone marrow and central nervous system infiltration, high levels of lactate dehydrogenase, and an elevated Ki67 expression in the tumor cells. Newer therapeutic approaches, including targeted therapy against BCL2, MYC, or other associated pathways, are needed. In addition, recent therapies that harness the immune system, such as checkpoint inhibitors and chimeric antigen receptor T-cell therapy, are changing the paradigm of treatment for non-Hodgkin lymphoma and could impact the outcome of DHL.

UI MeSH Term Description Entries
D011379 Prognosis A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations. Prognostic Factor,Prognostic Factors,Factor, Prognostic,Factors, Prognostic,Prognoses
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D015321 Gene Rearrangement The ordered rearrangement of gene regions by DNA recombination such as that which occurs normally during development. DNA Rearrangement,DNA Rearrangements,Gene Rearrangements,Rearrangement, DNA,Rearrangement, Gene,Rearrangements, DNA,Rearrangements, Gene
D016271 Proto-Oncogene Proteins c-myc Basic helix-loop-helix transcription factors encoded by the c-myc genes. They are normally involved in nucleic acid metabolism and in mediating the cellular response to growth factors. Elevated and deregulated (constitutive) expression of c-myc proteins can cause tumorigenesis. L-myc Proteins,N-myc Proteins,c-myc Proteins,myc Proto-Oncogene Proteins,p62(c-myc),Proto-Oncogene Products c-myc,Proto-Oncogene Proteins myc,myc Proto-Oncogene Product p62,p62 c-myc,L myc Proteins,N myc Proteins,Proteins myc, Proto-Oncogene,Proto Oncogene Products c myc,Proto Oncogene Proteins c myc,Proto Oncogene Proteins myc,Proto-Oncogene Proteins, myc,c myc Proteins,myc Proto Oncogene Product p62,myc Proto Oncogene Proteins,myc, Proto-Oncogene Proteins,p62 c myc
D016403 Lymphoma, Large B-Cell, Diffuse Malignant lymphoma composed of large B lymphoid cells whose nuclear size can exceed normal macrophage nuclei, or more than twice the size of a normal lymphocyte. The pattern is predominantly diffuse. Most of these lymphomas represent the malignant counterpart of B-lymphocytes at midstage in the process of differentiation. Diffuse Large B-Cell Lymphoma,Diffuse, Large B-Cell, Lymphoma,Histiocytic Lymphoma, Diffuse,Lymphoma, Histiocytic, Diffuse,Diffuse Large-Cell Lymphoma,Histiocytic Lymphoma,Large Lymphoid Lymphoma, Diffuse,Large-Cell Lymphoma, Diffuse,Lymphoma, Diffuse Large-Cell,Lymphoma, Histiocytic,Lymphoma, Large Cell, Diffuse,Lymphoma, Large Lymphoid, Diffuse,Lymphoma, Large-Cell, Diffuse,Diffuse Histiocytic Lymphoma,Diffuse Histiocytic Lymphomas,Diffuse Large B Cell Lymphoma,Diffuse Large Cell Lymphoma,Diffuse Large-Cell Lymphomas,Histiocytic Lymphomas,Large Cell Lymphoma, Diffuse,Lymphoma, Diffuse Histiocytic,Lymphoma, Diffuse Large Cell
D051560 Proto-Oncogene Proteins c-bcl-6 A DNA-binding protein that contains an N-terminal BTB (POZ) DOMAIN and C-terminal CYS2-HIS2 ZINC FINGERS. It represses GENETIC TRANSCRIPTION of target genes by recruiting HISTONE DEACETYLASES. Aberrant Blc-6 expression is associated with certain types of human B-CELL LYMPHOMA. bcl-6 Proto-Oncogene Proteins,c-bcl-6 Protein,c-bcl-6 Proto-Oncogene Proteins,B-Cell Lymphoma 6 Protein,Proto-Oncogene Protein bcl-6,Proto-Oncogene Protein c-bcl-6,Zinc Finger Protein 51,B Cell Lymphoma 6 Protein,Proto Oncogene Protein bcl 6,Proto Oncogene Protein c bcl 6,Proto Oncogene Proteins c bcl 6,Proto-Oncogene Proteins, bcl-6,Proto-Oncogene Proteins, c-bcl-6,bcl 6 Proto Oncogene Proteins,bcl-6, Proto-Oncogene Protein,c bcl 6 Protein,c bcl 6 Proto Oncogene Proteins,c-bcl-6, Proto-Oncogene Proteins
D058990 Molecular Targeted Therapy Treatments with drugs which interact with or block synthesis of specific cellular components characteristic of the individual's disease in order to stop or interrupt the specific biochemical dysfunction involved in progression of the disease. Targeted Molecular Therapy,Molecular Targeted Therapies,Molecular Therapy, Targeted,Targeted Molecular Therapies,Targeted Therapy, Molecular,Therapy, Molecular Targeted,Therapy, Targeted Molecular

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