title: Clonotypic analysis of immunoglobulin heavy chain sequences in patients with Waldenström's macroglobulinemia: correlation with MYD88 L265P somatic mutation status, clinical features, and outcome.
abstract: We performed IGH clonotypic sequence analysis in WM in order to determine whether a preferential IGH gene rearrangement was observed and to assess IGHV mutational status in blood and/or bone marrow samples from 36 WM patients. In addition we investigated the presence of MYD88 L265P somatic mutation. After IGH VDJ locus amplification, monoclonal VDJ rearranged fragments were sequenced and analyzed. MYD88 L265P mutation was detected by AS-PCR. The most frequent family usage was IGHV3 (74%); IGHV3-23 and IGHV3-74 segments were used in 26% and 17%, respectively. Somatic hypermutation was seen in 91% of cases. MYD88 L265P mutation was found in 65,5% of patients and absent in the 3 unmutated. These findings did not correlate with clinical findings and outcome. Conclusion. IGH genes' repertoire differed in WM from those observed in other B-cell disorders with a recurrent IGHV3-23 and IGHV3-74 usage; monoclonal IGHV was mutated in most cases, and a high but not omnipresent prevalence of MYD88 L265P mutation was observed. In addition, the identification of 3 patients with unmutated IGHV gene segments, negative for the MYD88 L265P mutation, could support the hypothesis that an extra-germinal B-cell may represent the originating malignant cell in this minority of WM patients.
authors.affiliation: Hematology Section of First Department of Propaedeutic Medicine, National and Kapodistrian University of Athens Medical School, Laikon Hospital, Agiou Thoma 17, 11527 Athens, Greece.
authors.forename: Loizos
authors.identifier: 0000-0002-8313-9141
authors.initials: L
authors.lastname: Petrikkos
authors.affiliation: Hematology Section of First Department of Propaedeutic Medicine, National and Kapodistrian University of Athens Medical School, Laikon Hospital, Agiou Thoma 17, 11527 Athens, Greece.
authors.forename: Marie-Christine
authors.identifier: 0000-0001-9805-9112
authors.initials: MC
authors.lastname: Kyrtsonis
authors.affiliation: Hematology Section of First Department of Propaedeutic Medicine, National and Kapodistrian University of Athens Medical School, Laikon Hospital, Agiou Thoma 17, 11527 Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Roumelioti
authors.affiliation: Hematology Section of First Department of Propaedeutic Medicine, National and Kapodistrian University of Athens Medical School, Laikon Hospital, Agiou Thoma 17, 11527 Athens, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Georgiou
authors.affiliation: Hematology Section of First Department of Propaedeutic Medicine, National and Kapodistrian University of Athens Medical School, Laikon Hospital, Agiou Thoma 17, 11527 Athens, Greece.
authors.forename: Anna
authors.identifier: 0000-0002-4052-7929
authors.initials: A
authors.lastname: Efthymiou
authors.affiliation: Hematology Section of First Department of Propaedeutic Medicine, National and Kapodistrian University of Athens Medical School, Laikon Hospital, Agiou Thoma 17, 11527 Athens, Greece.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Tzenou
authors.affiliation: Hematology Section of First Department of Propaedeutic Medicine, National and Kapodistrian University of Athens Medical School, Laikon Hospital, Agiou Thoma 17, 11527 Athens, Greece.
authors.forename: Panayiotis
authors.initials: P
authors.lastname: Panayiotidis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019943:Amino Acid Substitution; D001483:Base Sequence; D002999:Clone Cells; D004252:DNA Mutational Analysis; D019075:Electrophoresis, Capillary; D005260:Female; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics*; D016896:Treatment Outcome; D008258:Waldenstrom Macroglobulinemia / Q000235:genetics*
chemical_list: D007143:Immunoglobulin Heavy Chains; D053594:Myeloid Differentiation Factor 88