TP53 mutations are associated with mutated MYD88 and CXCR4, and confer an adverse outcome in Waldenström macroglobulinaemia
Authors:
- 5 September 2018
- journal article
- research article
- Published by Wiley in British Journal of Haematology
- Vol. 184 (2) , 242-245
Abstract
Summary: Little is known about TP53 mutations in Waldenström Macroglobulinaemia (WM). We evaluated 265 WM patients for TP53 mutations by next‐generation sequencing, and validated the findings by Sanger sequencing. TP53 mutations were identified and validated in 6 (2·6%) patients that impacted the DNA‐binding domain. All six were MYD88‐ and CXCR4‐mutated. Ibrutinib showed activity in patients carrying all three mutations. With a median follow‐up of 18 months, 2 (33%) with biallelic TP53 inactivation died of progressive disease. TP53 mutations are rare in WM, and associate with MYD88 and CXCR4 mutations. WM patients with TP53 mutations show response to ibrutinib.Keywords
Funding Information
- Leukemia and Lymphoma Society
This publication has 14 references indexed in Scilit:
- TP53 Mutation and Its Prognostic Significance in Waldenstrom's MacroglobulinemiaClinical Cancer Research, 2017
- Clonal Hematopoiesis Associated With Adverse Outcomes After Autologous Stem-Cell Transplantation for LymphomaJournal of Clinical Oncology, 2017
- Recommendations for the diagnosis and initial evaluation of patients with Waldenström Macroglobulinaemia: A Task Force from the 8th International Workshop on Waldenström MacroglobulinaemiaBritish Journal of Haematology, 2016
- Validation and Implementation of a Custom Next-Generation Sequencing Clinical Assay for Hematologic MalignanciesThe Journal of Molecular Diagnostics, 2016
- Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromesBlood, 2015
- Ibrutinib in Previously Treated Waldenström’s MacroglobulinemiaNew England Journal of Medicine, 2015
- Somatic mutations in MYD88 and CXCR4 are determinants of clinical presentation and overall survival in Waldenström macroglobulinemiaBlood, 2014
- The genomic landscape of Waldenström macroglobulinemia is characterized by highly recurring MYD88 and WHIM-like CXCR4 mutations, and small somatic deletions associated with B-cell lymphomagenesisBlood, 2014
- Chromosomal aberrations and their prognostic value in a series of 174 untreated patients with Waldenstrom's macroglobulinemiaHaematologica, 2012
- MYD88 L265P Somatic Mutation in Waldenström's MacroglobulinemiaNew England Journal of Medicine, 2012