Differential prognosis of single and multiple TP53 abnormalities in high-count MBL and untreated CLL

Rosalie Griffin, Julia E. Wiedmeier-Nutor, Sameer A. Parikh, Chantal E. McCabe, Daniel R. O’Brien, Nicholas J. Boddicker, Geffen Kleinstern, Kari G. Rabe, Laura Bruins, Sochilt Brown, Cecilia Bonolo de Campos, Wei Ding, Jose F. Leis, Paul J. Hampel, Timothy G. Call, Daniel L. Van Dyke, Neil E. Kay, James R. Cerhan, Huihuang Yan, Susan L. SlagerEsteban Braggio

Research output: Contribution to journalArticlepeer-review


TP53 aberrations, including mutations and deletion of 17p13, are important adverse prognostic markers in chronic lymphocytic leukemia (CLL) but are less studied in high count monoclonal B-cell lymphocytosis (HCMBL), an asymptomatic pre-malignant stage of CLL. Here we estimated the prevalence and impact of TP53 aberrations in 1,230 newly diagnosed treatment-naïve individuals (849 CLL, 381 HCMBL). We defined TP53 state as: wild-type (no TP53 mutations and normal 17p), single-hit (del(17p) or one TP53 mutation), or multi-hit (TP53 mutation and del(17p), TP53 mutation and loss of heterozygosity, or multiple TP53 mutations). Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for time to first treatment and overall survival by TP53 state. We found 64 (7.5%) CLL patients and 17 (4.5%) HCMBL individuals had TP53 mutations with variant allele fraction >10%. Del(17p) was present in 58 (6.8%) of CLL and 11 (2.9%) of HCMBL cases. Most individuals had wild-type (N=1,128, 91.7%) TP53 state, followed by multi-hit (N=55, 4.5%) and then single-hit (N=47, 3.8%) TP53 state. The risk of shorter time to therapy and death increased with the number of TP53 abnormalities. Compared to wild-type patients, multi-hit patients had 3-fold and single-hit patients had 1.5-fold increased risk of requiring therapy. Multi-hit patients also had 2.9-fold increased risk of death compared to wild-type. These results remained stable after accounting for other known poor prognostic factors. Both TP53 mutations and del(17p) may provide important prognostic information for HCMBL and CLL that would be missed if only one were measured.

Original languageEnglish
Pages (from-to)3169-3179
Number of pages11
JournalBlood Advances
Issue number13
StatePublished - 11 Jul 2023

Bibliographical note

Publisher Copyright:
© 2023 by The American Society of Hematology. Licensed under.


  • Having multiple TP53 abnormalities increased the risk of progression to therapy
  • Similar mutation frequency, type, and location in TP53 between 849 patients newly diagnosed with CLL and 381 patients with HCMBL
  • shortened the overall survival

ASJC Scopus subject areas

  • Hematology


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