Single-Cell Analysis and Next-Generation Immuno-Sequencing Show That Multiple Clones Persist in Patients with Chronic Lymphocytic Leukemia
| Autor: | Sara Beiggi, James B. Johnston, Tanner Mack, Linda M. Pilarski, Jitra Kriangkum, Hemalatha Kuppusamy, Sarah N. Motz, Eva Baigorri, Andrew Belch |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Adult
Male Chronic lymphocytic leukemia Gene Rearrangement B-Lymphocyte Heavy Chain Immunoglobulin Variable Region lcsh:Medicine Biology Somatic evolution in cancer immune system diseases hemic and lymphatic diseases medicine Humans lcsh:Science Aged Aged 80 and over Genetics B-Lymphocytes Multidisciplinary lcsh:R Macroglobulinemia Gene rearrangement Middle Aged Prognosis medicine.disease Leukemia Lymphocytic Chronic B-Cell Molecular biology Clone Cells Allelic exclusion Leukemia Immunoglobulin heavy chain Female lcsh:Q Single-Cell Analysis Immunoglobulin Heavy Chains IGHV@ Research Article |
| Zdroj: | PLoS ONE, Vol 10, Iss 9, p e0137232 (2015) PLoS ONE |
| ISSN: | 1932-6203 |
| Popis: | The immunoglobulin heavy chain (IGH) gene rearrangement in chronic lymphocytic leukemia (CLL) provides a unique molecular signature; however, we demonstrate that 26/198 CLL patients (13%) had more than one IGH rearrangement, indicating the power of molecular technology over phenotypic analysis. Single-cell PCR analysis and next-generation immuno-sequencing identified IGH-defined clones. In 23% (18/79) of cases whose clones carried unmutated immunoglobulin heavy chain variable (IGHV) genes (U-CLL), IGH rearrangements were bialleic with one productive (P) and one non-productive (NP) allele. Two U-CLL were biclonal, each clone being monoallelic (P). In 119 IGHV-mutated (M-CLL) cases, one had biallelic rearrangements in their CLL (P/NP) and five had 2-4 distinct clones. Allelic exclusion was maintained in all B-clones analyzed. Based on single-cell PCR analysis, 5/11 partner clones (45%) reached levels of >5x10(9) cells/L, suggesting second CLL clones. Partner clones persisted over years. Conventional IGH characterization and next-generation sequencing of 13 CLL, 3 multiple myeloma, 2 Waldenstrom's macroglobulinemia and 3 age-matched healthy donors consistently identified the same rearranged IGH sequences. Most multiple clones occurred in M-CLL, perhaps indicative of weak clonal dominance, thereby associating with a good prognosis. In contrast, biallelic CLL occurred primarily in U-CLL thus being associated with poor prognosis. Extending beyond intra-clonal diversity, molecular analysis of clonal evolution and apparent subclones in CLL may also reflect inter-clonal diversity. |
| Databáze: | OpenAIRE |
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