ATM and TP53 mutations show mutual exclusivity but distinct clinical impact in mantle cell lymphoma patients

Leuk Lymphoma. 2019 Jun;60(6):1420-1428. doi: 10.1080/10428194.2018.1542144. Epub 2019 Jan 10.


Mantle cell lymphoma (MCL) is characterized by the hallmark t(11;14)(q13;q32) translocation, leading to cyclin D1 over-expression. Additionally, disrupting the DNA damage response pathway through ATM or TP53 defects plays an important role in MCL pathogenesis. Using deep next-generation sequencing we analyzed the mutual composition of ATM and TP53 mutations in 72 MCL patients, and assessed their impact on progression-free survival (PFS) and overall survival (OS). Mutated ATM and TP53 alleles were found in 51% (37/72) and 22% (16/72) of the cases examined, respectively, with only three patients harboring mutations in both genes. Only a mutated TP53 gene was associated with the significantly reduced PFS and OS and the same output was observed when ATM and TP53 defective groups included also sole deletions 11q and 17p, respectively. Determining the exact ATM/p53 pathway dysfunction may influence the selection of MCL patients for innovative therapies based on the targeted inhibition of selected proteins.

Keywords: ATM; Mantle cell lymphoma; SOX11; TP53; p21; survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ataxia Telangiectasia Mutated Proteins / genetics*
  • Ataxia Telangiectasia Mutated Proteins / metabolism
  • Biomarkers, Tumor
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Humans
  • Lymphoma, Mantle-Cell / genetics*
  • Lymphoma, Mantle-Cell / mortality
  • Lymphoma, Mantle-Cell / pathology*
  • Lymphoma, Mantle-Cell / therapy
  • Male
  • Mutation*
  • Prognosis
  • SOXC Transcription Factors / genetics
  • SOXC Transcription Factors / metabolism
  • Sequence Deletion
  • Tumor Suppressor Protein p53 / genetics*
  • Tumor Suppressor Protein p53 / metabolism


  • Biomarkers, Tumor
  • SOX11 protein, human
  • SOXC Transcription Factors
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins