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.
IntroductionSeveral prognostic factors of chronic lymphocytic leukemia (CLL) have been identified, such as cytogenetic aberrations and recurrent gene mutations. B-cell receptor (BCR) signaling plays an important role in the tumorigenesis of CLL, and its clinical significance in predicting prognosis is also under study.MethodsTherefore, we assessed the already-known prognostic markers, immunoglobulin heavy chain (IGH) gene usage and the associations among these factors in 71 patients diagnosed with CLL in our center from October 2017 to March 2022. Sequencing of IGH gene rearrangements was performed using Sanger sequencing or IGH-based next-generation sequencing, and the results were further analyzed for distinct IGH/IGHD/IGHJ genes and the mutational status of the clonotypic IGHV (IGH variable) gene.ResultsIn summary, by analyzing the distribution of potential prognostic factors in CLL patients, we displayed a landscape of molecular profiles, confirmed the predictive value of recurrent genetic mutations and chromosome aberrations, and found that IGHJ3 was associated with favorable markers (mutated IGHV, trisomy 12), while IGHJ6 tended to correlate with unfavorable factors (unmutated IGHV, del17p).DiscussionThese results provided an indication for IGH gene sequencing in predicting the prognosis of CLL.
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