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Master Thesis

Genomic profile in anti-MAG neuropathies

Abstract : Background: Anti-MAG neuropathy is a rare acquired polyneuropathy associated with IgM monoclonal protein produces by an underlying B lymphoproliferative disorder. In mature small B-cell lymphoid neoplasms, genomic studies have revealed numerous clonal mutations. Patients and Methods: Samples from 27 anti-MAG neuropathy patients and 41 Waldenström’s macroglobulinemia (WM) controls were included in this study. MYD88L265P was detected using allele specific PCR. Mutational status of MYD88, CXCR4, TP53, SF3B1, ATM and NOTCH1 genes was assayed by targeted high throughput sequencing. Results: Lymphoproliferative disorders associated with anti-MAG neuropathy are 13 IgM monoclonal gammopathy of undetermined significance (IgM-MGUS), 12 WM, one splenic marginal zone lymphoma (MZL) and one monoclonal B-cell lymphocytosis. In this group, MYD88L265P is present in 53,8% of IgM-MGUS, 91,7% of WM and in the MZL. We identified 3,7%, 7,4% and 7,4% of variants in TP53, ATM and NOTCH1 respectively. There are no CXCR4 nor SF3B1 mutations. In WM control group, MYD88L265P is present in 95,2% of patients. TP53, ATM and SF3B1 variants were found in 7,3%, 7,3% and 4,9% of controls respectively. MYD88L265PCXCR4WHIM mutational profile (19,5%) is significantly associated to WM group (p<0,05). MYD88L265PCXCR4WHIM patients have lower hemoglobin, lower platelets count and higher bone marrow involvement than MYD88L265PCXCR4Wild-type patients (p<0,05 for all comparisons). Discussion: MYD88L265P mutation is highly observed in anti-MAG neuropathy. MYD88L265PCXCR4Wild-type status is associated with this paraneoplastic neuropathy and defines a new impact of mutational profile on clinical phenotypes associated with small B-cell lymphoid neoplasms. It may help to define new therapeutic options.
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Master Thesis
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Jean-Sébastien Allain. Genomic profile in anti-MAG neuropathies. Life Sciences [q-bio]. 2016. ⟨dumas-01755824⟩

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