Cell of origin of transformed follicular lymphoma
Follicular lymphoma (FL) is an indolent disease but transforms in 2% to 3% of patients per year into aggressive, large cell lymphoma, a critical event in the course of the disease associated with increased lymphoma-related mortality. Early transformation cannot be accurately predicted at the time of...
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| Veröffentlicht in: | Blood 2015-10, Vol.126 (18), p.2118-2127 |
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| creator | Kridel, Robert Mottok, Anja Farinha, Pedro Ben-Neriah, Susana Ennishi, Daisuke Zheng, Yvonne Chavez, Elizabeth A. Shulha, Hennady P. Tan, King Chan, Fong Chun Boyle, Merrill Meissner, Barbara Telenius, Adele Sehn, Laurie H. Marra, Marco A. Shah, Sohrab P. Steidl, Christian Connors, Joseph M. Scott, David W. Gascoyne, Randy D. |
| description | Follicular lymphoma (FL) is an indolent disease but transforms in 2% to 3% of patients per year into aggressive, large cell lymphoma, a critical event in the course of the disease associated with increased lymphoma-related mortality. Early transformation cannot be accurately predicted at the time of FL diagnosis and the biology of transformed FL (TFL) is poorly understood. Here, we assembled a cohort of 126 diagnostic FL specimens including 40 patients experiencing transformation ( |
| doi_str_mv | 10.1182/blood-2015-06-649905 |
| format | Article |
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•TFL is most commonly of the germinal center B-cell-like phenotype, but a significant minority of cases is of the ABC phenotype (16%).•The absence of BCL2 translocation in FL at diagnosis is associated with transformation into ABC-like large cell lymphoma.</description><identifier>ISSN: 0006-4971</identifier><identifier>EISSN: 1528-0020</identifier><identifier>DOI: 10.1182/blood-2015-06-649905</identifier><identifier>PMID: 26307535</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>B-Lymphocytes - metabolism ; B-Lymphocytes - pathology ; CARD Signaling Adaptor Proteins - genetics ; CD79 Antigens - genetics ; Cell Transformation, Neoplastic - genetics ; Cell Transformation, Neoplastic - pathology ; Female ; Germinal Center - metabolism ; Germinal Center - pathology ; Guanylate Cyclase - genetics ; Humans ; Lymphoid Neoplasia ; Lymphoma, Follicular - genetics ; Lymphoma, Follicular - pathology ; Male ; Middle Aged ; Mutation ; Myeloid Differentiation Factor 88 - genetics ; Proto-Oncogene Proteins c-bcl-2 - genetics</subject><ispartof>Blood, 2015-10, Vol.126 (18), p.2118-2127</ispartof><rights>2015 American Society of Hematology</rights><rights>2015 by The American Society of Hematology.</rights><rights>2015 by The American Society of Hematology 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c529t-edcec051953acd1175c6516a5be9bcae27e7131174ff1af7eb741fcd168bc97b3</citedby><cites>FETCH-LOGICAL-c529t-edcec051953acd1175c6516a5be9bcae27e7131174ff1af7eb741fcd168bc97b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26307535$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kridel, Robert</creatorcontrib><creatorcontrib>Mottok, Anja</creatorcontrib><creatorcontrib>Farinha, Pedro</creatorcontrib><creatorcontrib>Ben-Neriah, Susana</creatorcontrib><creatorcontrib>Ennishi, Daisuke</creatorcontrib><creatorcontrib>Zheng, Yvonne</creatorcontrib><creatorcontrib>Chavez, Elizabeth A.</creatorcontrib><creatorcontrib>Shulha, Hennady P.</creatorcontrib><creatorcontrib>Tan, King</creatorcontrib><creatorcontrib>Chan, Fong Chun</creatorcontrib><creatorcontrib>Boyle, Merrill</creatorcontrib><creatorcontrib>Meissner, Barbara</creatorcontrib><creatorcontrib>Telenius, Adele</creatorcontrib><creatorcontrib>Sehn, Laurie H.</creatorcontrib><creatorcontrib>Marra, Marco A.</creatorcontrib><creatorcontrib>Shah, Sohrab P.</creatorcontrib><creatorcontrib>Steidl, Christian</creatorcontrib><creatorcontrib>Connors, Joseph M.</creatorcontrib><creatorcontrib>Scott, David W.</creatorcontrib><creatorcontrib>Gascoyne, Randy D.</creatorcontrib><title>Cell of origin of transformed follicular lymphoma</title><title>Blood</title><addtitle>Blood</addtitle><description>Follicular lymphoma (FL) is an indolent disease but transforms in 2% to 3% of patients per year into aggressive, large cell lymphoma, a critical event in the course of the disease associated with increased lymphoma-related mortality. Early transformation cannot be accurately predicted at the time of FL diagnosis and the biology of transformed FL (TFL) is poorly understood. Here, we assembled a cohort of 126 diagnostic FL specimens including 40 patients experiencing transformation (<5 years) and 86 patients not experiencing transformation for at least 5 years. In addition, we assembled an overlapping cohort of 155 TFL patients, including 114 cases for which paired samples were available, and assessed temporal changes of routinely available biomarkers, outcome after transformation, as well as molecular subtypes of TFL. We report that the expression of IRF4 is an independent predictor of early transformation (Hazard ratio, 13.3; P < .001). We also show that composite histology at the time of transformation predicts favorable prognosis. Moreover, applying the Lymph2Cx digital gene expression assay for diffuse large B-cell lymphoma (DLBCL) cell-of-origin determination to 110 patients with DLBCL-like TFL, we demonstrate that TFL is of the germinal-center B-cell–like subtype in the majority of cases (80%) but that a significant proportion of cases is of the activated B-cell–like (ABC) subtype (16%). These latter cases are commonly negative for BCL2 translocation and arise preferentially from BCL2 translocation-negative and/or IRF4-expressing FLs. Our study demonstrates the existence of molecular heterogeneity in TFL as well as its relationship to the antecedent FL.
•TFL is most commonly of the germinal center B-cell-like phenotype, but a significant minority of cases is of the ABC phenotype (16%).•The absence of BCL2 translocation in FL at diagnosis is associated with transformation into ABC-like large cell lymphoma.</description><subject>B-Lymphocytes - metabolism</subject><subject>B-Lymphocytes - pathology</subject><subject>CARD Signaling Adaptor Proteins - genetics</subject><subject>CD79 Antigens - genetics</subject><subject>Cell Transformation, Neoplastic - genetics</subject><subject>Cell Transformation, Neoplastic - pathology</subject><subject>Female</subject><subject>Germinal Center - metabolism</subject><subject>Germinal Center - pathology</subject><subject>Guanylate Cyclase - genetics</subject><subject>Humans</subject><subject>Lymphoid Neoplasia</subject><subject>Lymphoma, Follicular - genetics</subject><subject>Lymphoma, Follicular - pathology</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>Myeloid Differentiation Factor 88 - genetics</subject><subject>Proto-Oncogene Proteins c-bcl-2 - genetics</subject><issn>0006-4971</issn><issn>1528-0020</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kM9OwzAMxiMEYmPwBgj1BQJx2iTrBQlN_JMmcYFzlKbOFpQ2U7pN2tvTMhhw4WTL9vfZ_hFyCewaYMpvqhBjTTkDQZmksihLJo7IGASfUsY4OyZjxvpOUSoYkbOue2cMipyLUzLiMmdK5GJMYIYhZNFlMfmFb4dsnUzbuZgarDMXQ_B2E0zKwq5ZLWNjzsmJM6HDi684IW8P96-zJzp_eXye3c2pFbxcU6wtWiagFLmxNYASVgqQRlRYVtYgV6gg7-uFc2CcwkoV4PpJOa1sqap8Qm73vqtN1QxubX9Y0KvkG5N2Ohqv_3Zav9SLuNWF5JKLvDco9gY2xa5L6A5aYHpAqD8R6gGhZlLvEfayq997D6JvZj-HYf_91mPSnfXYWqx9QrvWdfT_b_gArDOEuw</recordid><startdate>20151029</startdate><enddate>20151029</enddate><creator>Kridel, Robert</creator><creator>Mottok, Anja</creator><creator>Farinha, Pedro</creator><creator>Ben-Neriah, Susana</creator><creator>Ennishi, Daisuke</creator><creator>Zheng, Yvonne</creator><creator>Chavez, Elizabeth A.</creator><creator>Shulha, Hennady P.</creator><creator>Tan, King</creator><creator>Chan, Fong Chun</creator><creator>Boyle, Merrill</creator><creator>Meissner, Barbara</creator><creator>Telenius, Adele</creator><creator>Sehn, Laurie H.</creator><creator>Marra, Marco A.</creator><creator>Shah, Sohrab P.</creator><creator>Steidl, Christian</creator><creator>Connors, Joseph M.</creator><creator>Scott, David W.</creator><creator>Gascoyne, Randy D.</creator><general>Elsevier Inc</general><general>American Society of Hematology</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>20151029</creationdate><title>Cell of origin of transformed follicular lymphoma</title><author>Kridel, Robert ; 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Early transformation cannot be accurately predicted at the time of FL diagnosis and the biology of transformed FL (TFL) is poorly understood. Here, we assembled a cohort of 126 diagnostic FL specimens including 40 patients experiencing transformation (<5 years) and 86 patients not experiencing transformation for at least 5 years. In addition, we assembled an overlapping cohort of 155 TFL patients, including 114 cases for which paired samples were available, and assessed temporal changes of routinely available biomarkers, outcome after transformation, as well as molecular subtypes of TFL. We report that the expression of IRF4 is an independent predictor of early transformation (Hazard ratio, 13.3; P < .001). We also show that composite histology at the time of transformation predicts favorable prognosis. Moreover, applying the Lymph2Cx digital gene expression assay for diffuse large B-cell lymphoma (DLBCL) cell-of-origin determination to 110 patients with DLBCL-like TFL, we demonstrate that TFL is of the germinal-center B-cell–like subtype in the majority of cases (80%) but that a significant proportion of cases is of the activated B-cell–like (ABC) subtype (16%). These latter cases are commonly negative for BCL2 translocation and arise preferentially from BCL2 translocation-negative and/or IRF4-expressing FLs. Our study demonstrates the existence of molecular heterogeneity in TFL as well as its relationship to the antecedent FL.
•TFL is most commonly of the germinal center B-cell-like phenotype, but a significant minority of cases is of the ABC phenotype (16%).•The absence of BCL2 translocation in FL at diagnosis is associated with transformation into ABC-like large cell lymphoma.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>26307535</pmid><doi>10.1182/blood-2015-06-649905</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Blood, 2015-10, Vol.126 (18), p.2118-2127 |
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| subjects | B-Lymphocytes - metabolism B-Lymphocytes - pathology CARD Signaling Adaptor Proteins - genetics CD79 Antigens - genetics Cell Transformation, Neoplastic - genetics Cell Transformation, Neoplastic - pathology Female Germinal Center - metabolism Germinal Center - pathology Guanylate Cyclase - genetics Humans Lymphoid Neoplasia Lymphoma, Follicular - genetics Lymphoma, Follicular - pathology Male Middle Aged Mutation Myeloid Differentiation Factor 88 - genetics Proto-Oncogene Proteins c-bcl-2 - genetics |
| title | Cell of origin of transformed follicular lymphoma |
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