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MYELODYSPLASTIC NEOPLASM

Somatic TP53 single nucleotide variants, indels and copy number alterations in chronic myelomonocytic leukemia (CMML)

Leukemia volume 37, pages 1753–1756 (2023)Cite this article

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Chronic myelomonocytic leukemia (CMML) is a myelodysplastic/myeloproliferative overlap neoplasm characterized by sustained peripheral blood (PB) absolute (≥0.5 × 109/ l) and relative (≥10%) monocytosis, with <20% PB and bone marrow (BM) blasts [1, 2]. The somatic genetic landscape of CMML reflects a relationship to aging and clonal hematopoiesis, with mutations in TET2 (60%) and SRSF2 (50%) being early driver events. Clonal acquisition of gene mutations impacting epigenetic regulation, signaling and pre-mRNA splicing modulate disease phenotypes and prognosis.

TP53 (chromosome 17p.13.1) encodes a multifunctional protein pivotal to DNA damage response. TP53 alterations comprise mutations, which can cause dominant negative inactivation or gain of function oncogenic effects and copy number alterations (CNA) [3]. Mutations include single nucleotide variants (SNV) and insertion-deletion events (indels). In comparison to MDS (7%), AML (13%), therapy related MDS (t-MDS; 37%) and t-AML (28%), somatic TP53 mutations are infrequent in CMML (<5%) [4,5,6]. This is also true for t-CMML (9% of CMML cases), where the frequency of TP53 mutations is <5% [7]. The prevalence of TP53 mutations and somatic CNA, including allelic imbalances, however, have not been systematically evaluated in CMML patients.

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Fig. 1: Molecular spectrum of TP53 mutations in CMML and impact of TP53 alterations on overall survival.

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Please email the corresponding author for data requests.

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Acknowledgements

Lollipop plots were generated using ProteinPaint, St. Judes Children’s Research Hospital.

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Authors and Affiliations

  1. Division of Hematology, Mayo Clinic, Rochester, MN, USA

    Mark Gurney, Abhishek A. Mangaonkar, Terra Lasho, Christy Finke, Aref Al-Kali, Naseema Gangat, Mithun V. Shah, Hassan B. Alkhateeb, Ayalew Tefferi & Mrinal M. Patnaik

  2. Department of Malignant Hematology, Moffitt Cancer Center and Research Institute, Tampa, FL, USA

    David Sallman, Zhuoer Xie, Najla Al Ali, Rami Komrokji & Eric Padron

  3. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA

    David Viswanatha & Kaaren Reichard

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  1. Mark Gurney
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Contributions

MMP and EP conceived the study and contributed to design, analysis, and editing. MG conducted analysis and drafted manuscript. TL compiled and analyzed sequencing data. CF contributed to clinical data collection. NA conducted clinical data collection and contributed to analysis and editing. AAM, AA, ZX, DS, NG, MVS, HBA, AT, and RK contributed to analysis approach, interpretation and manuscript editing. DS and KR contributed to cytogenetic analysis, and manuscript editing. All authors reviewed the final manuscript and approved its submission.

Corresponding authors

Correspondence to Eric Padron or Mrinal M. Patnaik.

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Competing interests

MMP has received research funding from Kura Oncology, StemLine Pharmaceuticals and Epigenetix. He has served on the advisory board for CTI Pharmaceuticals.

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Gurney, M., Mangaonkar, A.A., Lasho, T. et al. Somatic TP53 single nucleotide variants, indels and copy number alterations in chronic myelomonocytic leukemia (CMML). Leukemia 37, 1753–1756 (2023). https://doi.org/10.1038/s41375-023-01964-3

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