TP53 mutations are associated with mutated MYD88 and CXCR4, and confer an adverse outcome in Waldenström macroglobulinaemia

Br J Haematol. 2019 Jan;184(2):242-245. doi: 10.1111/bjh.15560. Epub 2018 Sep 5.

Abstract

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: CXCR4; MYD88; TP53; Waldenström macroglobulinaemia; ibrutinib.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / analogs & derivatives
  • Adult
  • Aged
  • Disease-Free Survival
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Myeloid Differentiation Factor 88 / genetics*
  • Piperidines
  • Pyrazoles / administration & dosage*
  • Pyrimidines / administration & dosage*
  • Receptors, CXCR4 / genetics*
  • Survival Rate
  • Tumor Suppressor Protein p53 / genetics*
  • Waldenstrom Macroglobulinemia* / drug therapy
  • Waldenstrom Macroglobulinemia* / genetics
  • Waldenstrom Macroglobulinemia* / mortality

Substances

  • CXCR4 protein, human
  • MYD88 protein, human
  • Myeloid Differentiation Factor 88
  • Piperidines
  • Pyrazoles
  • Pyrimidines
  • Receptors, CXCR4
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • ibrutinib
  • Adenine