Genetic and functional drivers of diffuse large b cell lymphoma article pdf available in cell 1712. Hodgkin lymphoma originating from the germinal center, and it represents a heterogeneous group of diseases with variable outcomes that are differentially characterized by clinical features, cell of origin coo, molecular features, and most recently, frequently. Genetic and functional drivers of diffuse large b cell lymphoma anupama reddy, jenny zhang, nicholas s. Molecular subtypes of diffuse large b cell lymphoma are associated with distinct pathogenic mechanisms and. Diffuse large bcell lymphoma dlbcl, an aggressive form of nonhodgkin lymphoma, affects roughly 7 out of 100,000 people in the u. Diffuse large bcell lymphoma dlbcl this is the most common type of nonhodgkins lymphoma. Comparative molecular celloforigin classification of diffuse large b. The genetic landscape of diffuse large bcell lymphoma laura pasqualuccia and riccardo dallafaverab diffuse large bcell lymphoma dlbcl, the most common lymphoid malignancy in the western world, is an aggressive disease that remains incurable in approximately 30% of patients. Germinal center b cell like gcb, activated b cell like abc, and primary mediastinal b cell lymphoma pmbl.
It is an aggressive nhl in which survival without treatment is measured in months. Another study published in nutrition and cancer in 2015 looked at nutrition status in 262 patients with diffuse large b cell lymphoma dlbcl being treated with rchop chemotherapy rituxan, cyclophosphamide, doxorubicin, vincristine and prednisone. The world health organization who classification defines diffuse large bcell lymphoma dlbcl as a group of proliferations of large bcell lymphoid cells with a diffuse growth pattern. Although more than half of these patientsmayachievelongtermremission,themajorityofthere. These results revealed new driver dlbcl mutations, improving diagnostic. Dlbcl is an aggressive fastgrowing nhl that affects blymphocytes. Apr 15, 20 the world health organization who classification defines diffuse large bcell lymphoma dlbcl as a group of proliferations of large bcell lymphoid cells with a diffuse growth pattern.
Diffuse large bcell lymphoma lymphoma research foundation. Diffuse large b cell lymphoma dlbcl, the most common lymphoid malignancy in adults, is a clinically and genetically heterogeneous disease that is further classified into transcriptionally. Improving rchop in diffuse large bcell lymphoma is still a. Purpose highgrade bcell lymphoma with myc and bcl2 andor bcl6 rearrangements hgbldhth has a poor outcome after standard chemoimmunotherapy. We sought to understand the biologic underpinnings of hgbldhth with bcl2 rearrangements hgbldhthbcl2 and diffuse large bcell lymphoma dlbcl morphology through examination of gene expression. Genetic heterogeneity in large bcell lymphoma geneexpression profiling of 574 cases of diffuse large bcell lymphoma revealed four new subtypes based on the cooccurrence of mutation patterns. By analyzing dna copy profiles of 1,000 dlbcls, we identified gains of 18q21. The top false discovery rate fdrcorrected functional enrichments were identified by gene. Doublehit gene expression signature defines a distinct. The current gold standard of diffuse large b cell lymphoma dlbcl subclassification is based on gene expression profiling gep leading to three main molecular subtypes. Molecular complexity of diffuse large bcell lymphoma mdpi.
They travel around your body in your lymphatic system, helping you fight infections. Hodgkin lymphoma originating from the germinal center, and it represents a heterogeneous group of diseases with variable outcomes that are differentially characterized by clinical features, cell of origin coo, molecular features, and most recently, frequently recurring mutations. Since the introduction of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone rchop as the gold standard for the treatment of diffuse large b cell lymphoma, clinical investigators have constantly tried to improve its effectiveness by adding new drugs and proposing combinations ie, rchop plus drug x. Purpose highgrade b cell lymphoma with myc and bcl2 and or bcl6 rearrangements hgbldhth has a poor outcome after standard chemoimmunotherapy. Summary diffuse large b cell lymphoma dlbcl is the most common form of blood cancer and is characterized by a striking degree of genetic and clinical heterogeneity. Genetic and functional drivers of diffuse large b cell lymphoma a full list of authors and affiliations appears at the end of the article. Previous research into the genetic origins of dlbcl has been impeded by the significant heterogeneity of the disease, and the small sample size of past studies.
More than 18,000 people are diagnosed with dlbcl each year. Dlbcl is an aggressive fastgrowing nhl that affects b lymphocytes. Genetic and functional drivers of diffuse large bcell lymphoma. There were 3 discrete subsets of dlbcloxidative phosphorylation, bcell. Diffuse large bcell lymphoma genetic and rare diseases. Nov 09, 2017 diffuse large b cell lymphoma dlbcl, a form of nonhodgkin lymphoma, is the most common blood cancer. Diffuse large b cell lymphoma dlbcl is the most common histologic subtype of nonhodgkin lymphoma nhl, accounting for approximately 30 percent of patients with nhl. Miqe guidelines, designed to enhance experimental reproducibility and.
High pdl1 expression predicts poor prognosis in diffuse. Optimizing outcome prediction in diffuse large bcell. Chimeric antigen receptor cart cells are likely to change. It includes at least two distinct molecular subtypes, named after their putative cell of origin. Diffuse large b cell lymphoma dlbcl is the most common hematologic malignancy and is characterized by a striking degree of heterogeneity. Diffuse large b cell lymphoma dlbcl is the most common type of nonhodgkin lymphoma nhl in the united states and worldwide, accounting for about 22 percent of newly diagnosed cases of b cell nhl in the united states. Diffuse large bcell lymphomas dlbcls are phenotypically and genetically heterogeneous. This entity consists of cases that would have been classified as diffuse large cell lymphoma subtype g and immunoblastic lymphoma subtype h in the working formulation 2. Oct 20, 2017 diffuse large bcell lymphoma dlbcl is a type of blood cancer. Personalized risk prediction for eventfree survival at 24 months in patients with diffuse large bcell lymphoma. Worldwide, diffuse large b cell lymphoma represents the most common subtype of nonhodgkins lymphoma nhl and it accounts for 3040% of the newly diagnosed nhl. Molecular interaction between diffuse large b cell lymphoma tumor cells and tumor microenvironment, affecting the tumor pathogenesis. Genetic and functional drivers of diffuse large b cell lymphoma anupama.
We integrated these genetic drivers using consensus clustering and identified. Dlbcl occurs mostly in adults and is a fastgrowing aggressive lymphoma. Refining diffuse large bcell lymphoma subgroups using. Genetic and functional drivers of diffuse large b cell. Oct 05, 2017 genetic drivers of most common form of lymphoma identified. However, those that are refractory to, or relapse following, firstline therapy have a dismal outcome.
Here, we performed an integrative analysis of wholeexome. Distinct molecular profile of irf4rearranged large bcell. The promise of targeted therapy in cancer 52 year old female abc diffuse large b cell lymphoma activating mutation in b cell receptor subunit cd79b. Diffuse large b cell lymphoma dlbcl is the most common type of nonhodgkin lymphoma.
What is diffuse large bcell lymphoma dlbcl lymphoma is a type of blood cancer that develops when white blood cells called lymphocytes grow out of control. Diffuse large bcell lymphoma dlbcl is a type of blood cancer. Diffuse large b cell lymphoma dlbcl is the most common form of blood cancer and is characterized by a striking degree of genetic and clinical heterogeneity. Genetics and pathogenesis of diffuse large b cell lymphoma. It contains some specific entities and a large group of heterogeneous not otherwise specified diseases comprising morphologic variants and. Diffuse large bcell lymphoma dlbcl is the most common form of lymphoma and is curable in 60% of patients using a combination chemoimmunotherapy regimen, rchop 1, 2.
Antibody therapies for patients with diffuse large bcell. We enrolled a total of 1001 dlbcl patients and comprehensively defined the landscape of genetic mutations, copy number alterations and expression through wholeexome and transcriptome sequencing. Over the past decade, remarkable progress has been made in the understanding of the pathogenesis of this disease, spurred by the implementation of powerful genomic technologies that enabled the definition of its genetic and epigenetic landscape. This heterogeneity poses a major barrier to understanding the genetic basis of the disease and its response to therapy. Improving rchop in diffuse large bcell lymphoma is still. The illustrative scheme shows overview of molecular interaction with various cells constituting the tumor microenvironment, which affects the prognosis of the patients with diffuse large b cell lymphoma. Hodgkin lymphoma subtypes including the indolent follicular lymphoma and the aggressive, genetically heterogeneous diffuse large bcell lymphoma dlbcl.
Love,1 alexander waldrop,1 sirpa leppa, 3annika pasanen, leo meriranta, marjaliisa karjalainenlindsberg,3. Tzeng t, happ le, dave t, rajagopalan d, datta j, dunson db, dave ss 2017 genetic and functional drivers of diffuse large b cell lymphoma. To elucidate their genetic bases, we analyzed exome sequencing of 37 cutaneous dlbcls, including 31 dlbcls, leg type dlbcllt and 6 cutaneous dlbclsnot otherwise specified dlbclnos. Diffuse large b cell lymphoma dlbcl, the most prevalent form of b cell nonhodgkin lymphoma b nhl, is a phenotypically, genetically and clinically heterogeneous disease that arises from the malignant transformation of b cells in the germinal center gc. Germinal center bcell like gcb, activated bcell like abc, and primary mediastinal bcell lymphoma pmbl. Oct 05, 2017 genetic and functional drivers of diffuse large b cell lymphoma article pdf available in cell 1712. Diffuse large bcell lymphoma dlbcl is the most common type of nonhodgkin lymphoma nhl in the united states and worldwide, accounting for about 22 percent of newly diagnosed cases of bcell nhl in the united states. Genetic drivers of most common form of lymphoma identified. Diffuse large b cell lymphoma dlbcl is the most common subtype of lymphoma in the who classification, accounting for 31% of all lymphomas 1. Its an aggressive but treatable cancer that can involve lymph nodes and other organs. Integrating genomic alterations in diffuse large bcell lymphoma.
Pdf graphical abstract highlights d exome sequencing in 1001 dlbcl patients comprehensively identifies 150 driver genes d unbiased. Jan 10, 2016 b cell lymphoma refers to types of nonhodgkin lymphoma that are characterized by abnormalities of the b cells a type of white blood cell that makes antibodies to help fight infection. The condition may grow and spread slowly with few symptoms also known as indolent lymphoma or may be very aggressive with severe symptoms. Oct 30, 2017 diffuse large bcell lymphoma dlbcl this is the most common type of nonhodgkins lymphoma. Therapy of lymphoma inspired by functional and structural. Lymphomas occur when cells of the immune system, known as b lymphocytes, grow and multiply uncontrollably. Oct 06, 2017 researchers identify genetic drivers of common form of lymphoma research shows that more than 150 genetic mutations play a role in diffuse large b cell lymphoma. In this study body mass index bmi was found to be predictive of overall survival. Genetic and functional drivers of diffuse large b cell lymphoma. Bcell lymphoma refers to types of nonhodgkin lymphoma that are characterized by abnormalities of the bcells a type of white blood cell that makes antibodies to help fight infection. The importance of nutrition for lymphoma patients new.
Introduction diffuse large b cell lymphoma dlbcl is the most common hematologic malignancy, with an annual incidence of over 100,000 cases worldwide. For a reference copy of the document with all sections, see authorspoliciesreportingsummary flat. We sought to understand the biologic underpinnings of hgbldhth with bcl2 rearrangements hgbldhthbcl2 and diffuse large b cell lymphoma dlbcl morphology through examination of gene expression. To characterize the genetic and molecular heterogeneity of these tumors, we studied 31 diffuse lbcls dlbcls, not otherwise specified nos. Geneexpression profiling has identified subgroups of dlbcl activated bcelllike.
Genetics and pathogenesis of diffuse large bcell lymphoma nejm. Molecular subtypes of diffuse large b cell lymphoma are. Geneexpression profiling has identified subgroups of dlbcl activated b. Pdf diffuse large b cell lymphoma dlbcl is the most common form of blood cancer and is characterized by a striking degree of genetic and clinical. Pdf genetic and functional drivers of diffuse large b cell. Diffuse large b cell lymphoma dlbcl, the most common lymphoid. The current gold standard of diffuse large bcell lymphoma dlbcl subclassification is based on gene expression profiling gep leading to three main molecular subtypes.
Molecular subtypes of diffuse large b cell lymphoma are associated. Apr 30, 2018 diffuse large b cell lymphoma dlbcl, the most common lymphoid malignancy in adults, is a clinically and genetically heterogeneous disease that is further classified into transcriptionally. Lymphomas are the most common type of blood cancers. More accurate prognostic prediction in diffuse large bcell. Researchers identify genetic drivers of common form of lymphoma research shows that more than 150 genetic mutations play a role in diffuse large b cell lymphoma. It can start in the lymph nodes or outside of the lymphatic. The higher frequency of some subtypes such as lbcl with irf4 rearrangement lbclirf4 in children suggests that some agerelated biological differences may exist. Genetics of diffuse large bcell lymphoma blood american. Shown is the prevalence of the indicated genetic abnormalities in 72 genes in abc and gcb, along with the log 10 p value for the difference in prevalence between the two subgroups.
Genetics and pathogenesis of diffuse large bcell lymphoma. Pediatric large bcell lymphomas lbcls share morphological and phenotypic features with adult types but have better prognosis. The genetic landscape of diffuse large bcell lymphoma. Genetic heterogeneity in large b cell lymphoma geneexpression profiling of 574 cases of diffuse large b cell lymphoma revealed four new subtypes based on the cooccurrence of mutation patterns. Diffuse large bcell lymphoma dlbcl, a form of nonhodgkin lymphoma, is the most common blood cancer. A total of 761 potential driver mutations were identified in 89 out of the 106 genes with a similar number in gcb and abc dlbcl.
Diffuse large bcell lymphoma dlbcl is a heterogenous blood. More accurate prognostic prediction in diffuse large b. Panel a shows genetic aberrations that distinguish the activated bcell like abc and germinalcenter bcell like gcb subgroups of diffuse large bcell lymphoma dlbcl. Researchers identify genetic drivers of common form of. Oct 26, 2017 diffuse large b cell lymphoma dlbcl, an aggressive form of nonhodgkin lymphoma, affects roughly 7 out of 100,000 people in the u. Diffuse large bcell lymphoma dlbcl, the most frequent subtype of lymphoid malignancy, remains a significant clinical challenge, as. Genomic analyses identify recurrent alterations in immune. Diffuse large b cell lymphoma dlbcl, the most prevalent form of b cell nonhodgkin lymphoma bnhl, is a phenotypically, genetically and clinically heterogeneous disease that arises from the malignant transformation of b cells in the germinal center gc. Molecular interaction between diffuse large bcell lymphoma tumor cells and tumor microenvironment, affecting the tumor pathogenesis. More than 150 genetic mutations play a role in diffuse large b cell lymphoma. Love, alexander waldrop, sirpa leppa, annika pasanen.
Pdf molecular profiling of diffuse large bcell lymphoma identifies. Bcell lymphoma genetic and rare diseases information. Genetic and functional drivers of diffuse large b cell lymphoma anupama reddy, 1,2,22jenny zhang, nicholas s. The illustrative scheme shows overview of molecular interaction with various cells constituting the tumor microenvironment, which affects the prognosis of the patients with diffuse large bcell lymphoma. Jun 19, 2019 the activated bcell abclike subtype of diffuse large bcell lymphoma dlbcl is characterized by the chronic activation of signaling initiated by immunoglobulin. To characterize the genetic and molecular heterogeneity of these tumors, we studied 31. Diffuse large b cell lymphoma, activated bcell, germinal center bcell, myc, bcl6 and bcl2 oncogenes, rchop, daepochr. Diffuse large bcell lymphoma dlbcl is the most common subtype of lymphoma in the who classification, accounting for 31% of all lymphomas 1.
Cutaneous diffuse large bcell lymphomas dlbcls are aggressive lymphomas with a poor prognosis. Pdf genetic and functional drivers of diffuse large b. Since the introduction of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone rchop as the gold standard for the treatment of diffuse large bcell lymphoma, clinical investigators have constantly tried to improve its effectiveness by adding new drugs and proposing combinations ie, rchop plus drug x. Scientists identify genetic drivers of common lymphoma. Resource genetic and functional drivers of diffuse large b cell lymphoma anupama reddy, 1,2,22jenny zhang, nicholas s. G et al 2014 high level of soluble programmed cell death ligand 1 in blood impacts overall survival in aggressive diffuse large bcell lymphoma.
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