Immunoglobulin gene rearrangement IGHV3-48 is a predictive marker of histological transformation into aggressive lymphoma in follicular lymphomas

García‐Álvarez, María; Alonso‐Álvarez, Sara; Prieto-Conde, Isabel; Jiménez, Cristina; Sarasquete, María Eugenia; Chillón, María Carmen; Medina, Alejandro; Balanzategui, Ana; Maldonado, Rebeca; Antón, Alicia; Puig, Noemí; Rodríguez, Marta; Blanco, Óscar; Tamayo, Pilar; González-Calle, Verónica; Martı́n, Alejandro; González, Marcos; Caballero, Marı́a Dolores; Alcoceba, Miguel

doi:10.1038/s41408-019-0213-9

Cited by 12 publications

(16 citation statements)

References 56 publications

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“…IGHV3-23 is one of the most commonly used heavy variable regions in the human immunoglobulin (Ig) repertoire [ 30 ]. Its usage has been linked with non-Hodgkin lymphomas (NHL) such as chronic lymphoid leukemia (CLL) [ 31 – 34 ], mantle cell lymphoma (MCL) [ 35 ], splenic marginal zone lymphoma (MZL) [ 36 , 37 ], Waldenström’s macroglobulinemia [ 38 ], and follicular lymphoma (FL) [ 39 , 40 ]. Disease progression in these B-cell malignancies is driven by chronic stimulation from either microbial or auto-antigens.…”

Section: Discussionmentioning

confidence: 99%

Plasma proteomic profiling suggests an association between antigen driven clonal B cell expansion and ME/CFS

et al. 2020

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Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is an unexplained chronic, debilitating illness characterized by fatigue, sleep disturbances, cognitive dysfunction, orthostatic intolerance and gastrointestinal problems. Using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), we analyzed the plasma proteomes of 39 ME/CFS patients and 41 healthy controls. Logistic regression models, with both linear and quadratic terms of the protein levels as independent variables, revealed a significant association between ME/CFS and the immunoglobulin heavy variable (IGHV) region 3-23/ 30. Stratifying the ME/CFS group based on self-reported irritable bowel syndrome (sr-IBS) status revealed a significant quadratic effect of immunoglobulin lambda constant region 7 on its association with ME/CFS with sr-IBS whilst IGHV3-23/30 and immunoglobulin kappa variable region 3-11 were significantly associated with ME/CFS without sr-IBS. In addition, we were able to predict ME/CFS status with a high degree of accuracy (AUC = 0.774-0.838) using a panel of proteins selected by 3 different machine learning algorithms: Lasso, Random Forests, and XGBoost. These algorithms also identified proteomic profiles that predicted the status of ME/CFS patients with sr-IBS (AUC = 0.806-0.846) and ME/CFS without sr-IBS (AUC = 0.754-0.780). Our findings are consistent with a significant association of ME/CFS with immune dysregulation and highlight the potential use of the plasma proteome as a source of biomarkers for disease.

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Section: Discussionmentioning

confidence: 99%

Plasma proteomic profiling suggests an association between antigen driven clonal B cell expansion and ME/CFS

et al. 2020

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“…D3-10, D3-22, and D3-3 accounted for most of the D2 and D3 gene families used in FL. JH4 was the most frequent JH component [ 58 , 69 , 80 ]. Interestingly, FL can transform into other more aggressive malignancies, usually DLBCL.…”

Section: The Oncogenesis Of B-lineage Malignancies and The Correspond...mentioning

confidence: 99%

Next-generation sequencing for MRD monitoring in B-lineage malignancies: from bench to bedside

et al. 2022

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Minimal residual disease (MRD) is considered the strongest relevant predictor of prognosis and an effective decision-making factor during the treatment of hematological malignancies. Remarkable breakthroughs brought about by new strategies, such as epigenetic therapy and chimeric antigen receptor-T (CAR-T) therapy, have led to considerably deeper responses in patients than ever, which presents difficulties with the widely applied gold-standard techniques of MRD monitoring. Urgent demands for novel approaches that are ultrasensitive and provide sufficient information have put a spotlight on high-throughput technologies. Recently, advances in methodology, represented by next-generation sequencing (NGS)-based clonality assays, have proven robust and suggestive in numerous high-quality studies and have been recommended by some international expert groups as disease-monitoring modalities. This review demonstrates the applicability of NGS-based clonality assessment for MRD monitoring of B-cell malignancies by summarizing the oncogenesis of neoplasms and the corresponding status of immunoglobulin (IG) rearrangements. Furthermore, we focused on the performance of NGS-based assays compared with conventional approaches and the interpretation of results, revealing directions for improvement and prospects in clinical practice.

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“…This finding could suggest that cases with IGHV4-34 usage may tend to transform to a more aggressive disease rather than relapsing as FL, a hypothesis supported by the presence of this IGHV gene in a proportion of DLBCL and transformed FL. 29,31,42 If independently confirmed in larger cohorts, this feature might help to improve the molecular stratification of FL.…”

Section: Discussionmentioning

confidence: 87%

Follicular lymphoma subgroups with and without t(14;18) differ in their N-glycosylation pattern and IGHV usage

et al. 2021

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We previously reported that t(14;18)-negative follicular lymphomas (FL) show a clear reduction of newly acquired N-glycosylation sites (NANGS) in immunoglobulin genes. We therefore aimed to investigate in-depth the occurrence of NANGS in a larger cohort of t(14;18)-positive and t(14;18)-negative FL, including early (I/II) and advanced (III/IV) stage treatment naïve and relapsed tumors. We determined the clonotype using a next generation sequencing approach in a series of 68 FL with fresh frozen material (36 t(14;18)-positive and 32 t(14;18)-negative). The frequency of NANGS differed considerably between t(14;18)-positive and t(14;18)-negative FL III/IV, but no difference was observed among t(14;18)-positive and t(14;18)-negative FL I/II. The introduction of NANGS in all t(14;18)-negative clinical subgroups occurred significantly more often in the FR3 region. Moreover, t(14;18)-negative treatment naïve FL, specifically those with NANGS, showed a strong bias for IGHV4-34 usage compared to t(14;18)-positive treatment naïve cases with NANGS, while IGHV4-34 usage was never found in relapsed FL. In conclusion, subgroups of t(14;18)-negative FL might use different mechanisms of BCR stimulation compared to the lectin-mediated binding described in t(14;18)-positive FL, including responsiveness to autoantigens as indicated by biased IGHV4-34 usage and strong NANGS enrichment in FR3.

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Immunoglobulin gene rearrangement IGHV3-48 is a predictive marker of histological transformation into aggressive lymphoma in follicular lymphomas

Cited by 12 publications

References 56 publications

Plasma proteomic profiling suggests an association between antigen driven clonal B cell expansion and ME/CFS

Plasma proteomic profiling suggests an association between antigen driven clonal B cell expansion and ME/CFS

Next-generation sequencing for MRD monitoring in B-lineage malignancies: from bench to bedside

Follicular lymphoma subgroups with and without t(14;18) differ in their N-glycosylation pattern and IGHV usage

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