Abstract
The somatic hypermutation (SHM) status of the clonotypic immunoglobulin heavy variable (IGHV) gene is a critical biomarker for assessing the prognosis of patients with chronic lymphocytic leukemia (CLL). Importantly, independent studies have documented that IGHV SHM status is also a predictor of responses to therapy, including both chemoimmunotherapy (CIT) and novel, targeted agents. Moreover, immunogenetic analysis in CLL has revealed that different patients may express (quasi)identical, stereotyped B cell receptor immunoglobulin (BcR IG) and are classified into subsets based on this common feature. Patients in certain stereotyped subsets display consistent biology, clinical presentation, and outcome that are distinct from other patients, even with concordant IGHV gene SHM status. All of the above highlights the relevance of immunogenetic analysis in CLL, which is considered a cornerstone for accurate risk stratification and clinical decision making. Recommendations for robust immunogenetic analysis exist thanks to dedicated efforts by ERIC, the European Research Initiative on CLL, covering all test phases, from the pre-analytical and analytical to the post-analytical, pertaining to the analysis, interpretation, and reporting of the findings. That said, these recommendations apply to Sanger sequencing, which is increasingly being superseded by next generation sequencing (NGS), further underscoring the need for an update. Here, we present an overview of the clinical utility of immunogenetics in CLL and update our analytical recommendations with the aim to assist in the refined management of patients with CLL.
| Original language | English |
|---|---|
| Pages (from-to) | 1961-1968 |
| Number of pages | 8 |
| Journal | Leukemia |
| Volume | 36 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - Aug 2022 |
Bibliographical note
Acknowledgements:ERIC is the WP7 on CLL of the European Leukemia Net (ELN) and the SWG on CLL of the European Hematology Association (EHA). This work has been supported in part by: the Hellenic Precision Medicine Network in Oncology, a flagship initiative of the General Secretariat of Research and Innovation of Greece; the Hellenic Foundation for Research and Innovation (HFRI) and the General Secretariat for Research and Innovation of Greece, under grant agreement No 336 (Project CLLon); the project ODYSSEAS (Intelligent and Automated Systems for enabling the Design, Simulation and Development of Integrated Processes and Products) implemented under the “Action for the Strategic Development on the Research and Technological Sector”, funded by the Operational Programme “Competitiveness, Entrepreneurship and Innovation” (NSRF 2014–2020) and co-financed by Greece and the European Union, with grant agreement no: MIS 5002462; the Swedish Cancer Society, the Swedish Research Council, the Knut and Alice Wallenberg Foundation, Karolinska Institutet, Karolinska University Hospital, and Radiumhemmets Forskningsfonder, Stockholm; Associazione Italiana per la Ricerca sul Cancro—AIRC, Milano, Italy (Special Program on Metastatic Disease—5 per mille #21198); TRANSCAN 2/NOVEL funded under JTC 2016 from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 643638.
Publisher Copyright: © 2022, The Author(s).
