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Acute myeloid leukemia

Comparison of clinical and molecular characteristics of patients with acute myeloid leukemia and either TP73 or TP53 mutations

Leukemia volume 35, pages 1188–1192 (2021)Cite this article

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The transcription factor p53, described as the “guardian of the genome”, becomes activated in response to malignancy-associated stress signals resulting in cell cycle arrest, senescence, differentiation, or apoptosis leading to the inhibition of tumor cell growth [1]. Inactivation of the p53 tumor-suppressor pathway is among the most common escape mechanisms allowing survival of malignant cells subjected to cytotoxic stress [2]. Inactivating TP53 mutations have been detected in ≤50% of cancers [3].

Acute myeloid leukemia (AML) is an aggressive bone marrow (BM) malignancy associated with poor long-term survival in most patients. Somatic TP53 mutations occur in AML less frequently than in solid tumors, in 5–10% of de novo and ~33% of therapy-related or secondary AML cases [4,5,6,7]. They are associated with older age and poor-risk cytogenetic abnormalities [e.g., −5/del(5q), −7/del(7q) and complex karyotype, especially a “typical” complex karyotype] [8]. Patients with TP53 mutations have very poor outcomes, with complete remission (CR) rates of 20–40% and median overall survival (OS) of 5–9 months [5, 8, 9]. Even for patients attaining a CR, allogeneic stem cell transplantation (alloSCT) yields inadequate results with 3-year OS rates of 10–12% [10].

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Fig. 1: TP73 and TP53 Mutation lollipop plots.
Fig. 2: Kaplan-Meier survival curves.

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Acknowledgements

The authors are grateful to the patients who consented to participate in these clinical trials and the families who supported them; to Donna Bucci and the CALGB/Alliance Leukemia Tissue Bank at The Ohio State University Comprehensive Cancer Center, Columbus, OH, for sample processing and storage services and Lisa J. Sterling for data management. This work was supported in part by the National Cancer Institute (grants UG1CA233338 (JCB), CA101140, CA140158, CA180861, CA196171, CA016058, CA180821, CA180882, U24CA196171, R35CA198183 (to JCB) and CA077658), the Leukemia Clinical Research Foundation, the Warren D. Brown Foundation, the Alliance Clinical Scholar program (to ASM), and by an allocation of computing resources from The Ohio Supercomputer Center.

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Author notes

  1. These authors contributed equally: John C. Byrd, Clara D. Bloomfield

Authors and Affiliations

  1. The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA

    Alice S. Mims, Jessica Kohlschmidt, Ann-Kathrin Eisfeld, Krzysztof Mrόzek, James S. Blachly, Shelley Orwick, Dimitrios Papaioannou, Deedra Nicolet, Deepa Sampath, John C. Byrd & Clara D. Bloomfield

  2. Alliance Statistics and Data Center, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA

    Jessica Kohlschmidt & Deedra Nicolet

  3. Dana–Farber Cancer Institute, Boston, MA, USA

    Richard M. Stone

  4. Wake Forest Baptist Comprehensive Cancer Center, Winston-Salem, NC, USA

    Bayard L. Powell

  5. Monter Cancer Center, Hofstra Northwell School of Medicine, Lake Success, NY, USA

    Jonathan E. Kolitz

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  1. Alice S. Mims
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Contributions

ASM, JK, A-KE, KM, JCB, and CDB contributed to the study design; ASM, JK, A-KE, KM, JCB, and CDB contributed to the data interpretation, ASM, KM, JK, JCB, and CDB wrote the paper; ASM, A-KE, SO, DP, and DS performed laboratory-based research; JSB performed the data processing; JK and DN performed statistical analysis; RMS, BLP, JEK, KM, JCB, and CDB were involved directly or indirectly in the care of patients and/or sample procurement. All authors read and agreed on the final version of the paper. The authors dedicate this letter to CDB, who died unexpectedly as this paper was being completed. Her mentorship and support fostered all of us to pursue novel approaches to improve outcome for AML patients.

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Correspondence to Alice S. Mims.

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Mims, A.S., Kohlschmidt, J., Eisfeld, AK. et al. Comparison of clinical and molecular characteristics of patients with acute myeloid leukemia and either TP73 or TP53 mutations. Leukemia 35, 1188–1192 (2021). https://doi.org/10.1038/s41375-020-1007-6

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