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Clonotypic analysis of immunoglobulin heavy chain sequences in patients with Waldenström's macroglobulinemia: correlation with MYD88 L265P somatic mutation status, clinical features, and outcome.
Biomed Res Int. 2014; 2014:809103.BR

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+Show Affiliations

Hematology Section of First Department of Propaedeutic Medicine, National and Kapodistrian University of Athens Medical School, Laikon Hospital, Agiou Thoma 17, 11527 Athens, Greece.Hematology Section of First Department of Propaedeutic Medicine, National and Kapodistrian University of Athens Medical School, Laikon Hospital, Agiou Thoma 17, 11527 Athens, Greece.Hematology Section of First Department of Propaedeutic Medicine, National and Kapodistrian University of Athens Medical School, Laikon Hospital, Agiou Thoma 17, 11527 Athens, Greece.Hematology Section of First Department of Propaedeutic Medicine, National and Kapodistrian University of Athens Medical School, Laikon Hospital, Agiou Thoma 17, 11527 Athens, Greece.Hematology Section of First Department of Propaedeutic Medicine, National and Kapodistrian University of Athens Medical School, Laikon Hospital, Agiou Thoma 17, 11527 Athens, Greece.Hematology Section of First Department of Propaedeutic Medicine, National and Kapodistrian University of Athens Medical School, Laikon Hospital, Agiou Thoma 17, 11527 Athens, Greece.Hematology Section of First Department of Propaedeutic Medicine, National and Kapodistrian University of Athens Medical School, Laikon Hospital, Agiou Thoma 17, 11527 Athens, Greece.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

25197661

Citation

Petrikkos, Loizos, et al. "Clonotypic Analysis of Immunoglobulin Heavy Chain Sequences in Patients With Waldenström's Macroglobulinemia: Correlation With MYD88 L265P Somatic Mutation Status, Clinical Features, and Outcome." BioMed Research International, vol. 2014, 2014, p. 809103.
Petrikkos L, Kyrtsonis MC, Roumelioti M, et al. Clonotypic analysis of immunoglobulin heavy chain sequences in patients with Waldenström's macroglobulinemia: correlation with MYD88 L265P somatic mutation status, clinical features, and outcome. Biomed Res Int. 2014;2014:809103.
Petrikkos, L., Kyrtsonis, M. C., Roumelioti, M., Georgiou, G., Efthymiou, A., Tzenou, T., & Panayiotidis, P. (2014). Clonotypic analysis of immunoglobulin heavy chain sequences in patients with Waldenström's macroglobulinemia: correlation with MYD88 L265P somatic mutation status, clinical features, and outcome. BioMed Research International, 2014, 809103. https://doi.org/10.1155/2014/809103
Petrikkos L, et al. Clonotypic Analysis of Immunoglobulin Heavy Chain Sequences in Patients With Waldenström's Macroglobulinemia: Correlation With MYD88 L265P Somatic Mutation Status, Clinical Features, and Outcome. Biomed Res Int. 2014;2014:809103. PubMed PMID: 25197661.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Clonotypic analysis of immunoglobulin heavy chain sequences in patients with Waldenström's macroglobulinemia: correlation with MYD88 L265P somatic mutation status, clinical features, and outcome. AU - Petrikkos,Loizos, AU - Kyrtsonis,Marie-Christine, AU - Roumelioti,Maria, AU - Georgiou,George, AU - Efthymiou,Anna, AU - Tzenou,Tatiana, AU - Panayiotidis,Panayiotis, Y1 - 2014/08/14/ PY - 2014/04/18/received PY - 2014/07/12/accepted PY - 2014/9/9/entrez PY - 2014/9/10/pubmed PY - 2015/6/30/medline SP - 809103 EP - 809103 JF - BioMed research international JO - Biomed Res Int VL - 2014 N2 - 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. SN - 2314-6141 UR - https://www.unboundmedicine.com/medline/citation/25197661/Clonotypic_analysis_of_immunoglobulin_heavy_chain_sequences_in_patients_with_Waldenström's_macroglobulinemia:_correlation_with_MYD88_L265P_somatic_mutation_status_clinical_features_and_outcome_ L2 - https://dx.doi.org/10.1155/2014/809103 DB - PRIME DP - Unbound Medicine ER -