Nature and nurture: a case of transcending haematological pre-malignancies in a pair of monozygotic twins adding possible clues on the pathogenesis of B-cell proliferations
| Autor: | Anne Stidsholt Roug, Charlotte Guldborg Nyvold, Peter Hokland, Eigil Kjeldsen, Palle Villesen, Line Nederby, Marcus Celik Hansen |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
PLCB1 Chronic lymphocytic leukaemia Lymphocytosis Somatic cell Leukemia Lymphocytic Chronic B-Cell/diagnosis Biology Germline Myeloid Neoplasm Lymphocytosis/genetics Immunophenotyping hemic and lymphatic diseases medicine Humans Genetic Predisposition to Disease Exome Immunoglobulin Heavy Chains/genetics JAK2 mutation B cell Exome sequencing Germ-Line Mutation Aged Genetics Comparative Genomic Hybridization Customized exome analysis Hematology Twins Monozygotic Leukemia Lymphocytic Chronic B-Cell Monoclonal B-cells medicine.anatomical_structure Monoclonal Immunology Somatic Hypermutation Immunoglobulin medicine.symptom Immunoglobulin Heavy Chains Precancerous Conditions Monozygotic twins |
| Zdroj: | Hansen, M C, Nyvold, C G, Roug, A S, Kjeldsen, E, Villesen, P, Nederby, L & Hokland, P 2015, ' Nature and nurture: a case of transcending haematological pre-malignancies in a pair of monozygotic twins adding possible clues on the pathogenesis of B-cell proliferations ', British Journal of Haematology, vol. 169, no. 3, pp. 391–400 . https://doi.org/10.1111/bjh.13305 |
| DOI: | 10.1111/bjh.13305 |
| Popis: | We describe a comprehensive molecular analysis of a pair of monozygotic twins, who came to our attention when one experienced amaurosis fugax and was diagnosed with JAK2+ polycythaemia vera. He (Twin A) was also found to have an asymptomatic B-cell chronic lymphocytic leukaemia (B-CLL). Although JAK2-, Twin B was subsequently shown to have a benign monoclonal B-cell lymphocytosis (MBL). Flow cytometric and molecular analyses of the B-cell compartments revealed different immunoglobulin light and heavy chain usage in each twin. We hypothesized that whole exome sequencing could help delineating the pattern of germline B-cell disorder susceptibility and reveal somatic mutations potentially contributing to the differential patterns of pre-malignancy. Comparing bone marrow cells and T cells and employing in-house engineered integrative analysis, we found aberrations in Twin A consistent with a myeloid neoplasm, i.e. in TET2, RUNX1, PLCB1 and ELF4. Employing the method for detecting high-ranking variants by extensive annotation and relevance scoring, we also identified shared germline variants in genes of proteins interacting with B-cell receptor signalling mediators and the WNT-pathway, including IRF8, PTPRO, BCL9L, SIT1 and SIRPB1, all with possible implications in B-cell proliferation. Similar patterns of IGHV-gene usage to those demonstrated here have been observed in inherited acute lymphoblastic leukaemia. Collectively, these findings may help in facilitating identification of putative master gene(s) involved in B-cell proliferations in general and MBL and B-CLL in particular. |
| Databáze: | OpenAIRE |
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