Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2018 Dec;31(4):379-383.
doi: 10.1016/j.beha.2018.09.010. Epub 2018 Sep 20.

Patterns of mutations in TP53 mutated AML

John S Welch  1
Affiliations
Review

Patterns of mutations in TP53 mutated AML

John S Welch. Best Pract Res Clin Haematol. 2018 Dec.

Abstract

TP53 mutated acute myeloid leukemia (AML) responds poorly to chemotherapy and has a short overall survival rate with a median of 5-9 months. Poor outcomes in TP53 mutated AML following chemotherapy have been observed and treatment options remain limited, although the presence of TP53 mutations alone should not be a barrier to therapy. Decitabine is emerging as an alternative treatment option for patients with TP53 mutated AML, although the agent has not been associated with deep molecular remissions and requires additional consolidation. The clinical and genomic characteristics of TP53 mutated AML are reviewed in this paper.

Keywords: AML; Acute myeloid leukemia; CHIP; Clonal hematopoiesis of indeterminate potential; Decitabine; MDS; Mutation patterns; Myelodysplastic syndromes; TP53.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest

The author declares no conflicts of interest.

Figures

Figure 1.
Figure 1.
A. The number of Tier 1 (exome) mutations observed in AML patients evaluated at Washington University using exome sequencing [32, 34]. Cases highlighted in red had associated TP53 mutations. Cases in black had TP53 wild-type. B. Mutation spectrum from patients described in A. C and D. Mutation co-occurrence patterns in AML patients with TP53 mutations from published series [5, 6, 32, 34]. These segregated into two groups: cases with TP53 mutations and mutations in mutations in TP53 and epigenetic genes (DNMT3A, TET2, IDH1, IDH2) and transcription factors (NPM1, CEBPA, RUNX1) typically co-localized to the founding clone (C), whereas mutations in activated signaling pathways (FLT3, RAS, PTPN11, BCOR, JAK2, NF1) and in polycomb pathways (SF3B1, KDM6A, SRSF2) occurred typically in subclones of the TP53 mutant clone (D).
See this image and copyright information in PMC

References

    1. Yanada M, Yamamoto Y, Iba S, Okamoto A, Inaguma Y, Tokuda M, et al. TP53 mutations in older adults with acute myeloid leukemia. Int J Hematol 2016;103:429–35. - PubMed
    1. Hou HA, Chou WC, Kuo YY, Liu CY, Lin LI, Tseng MH, et al. TP53 mutations in de novo acute myeloid leukemia patients: longitudinal follow-ups show the mutation is stable during disease evolution. Blood Cancer J 2015;5:e331. - PMC - PubMed
    1. Rucker FG, Schlenk RF, Bullinger L, Kayser S, Teleanu V, Kett H, et al. TP53 alterations in acute myeloid leukemia with complex karyotype correlate with specific copy number alterations, monosomal karyotype, and dismal outcome. Blood 2012;119:2114–21. - PubMed
    1. Stengel A, Kern W, Haferlach T, Meggendorfer M, Fasan A, Haferlach C. The impact of TP53 mutations and TP53 deletions on survival varies between AML, ALL, MDS and CLL: an analysis of 3307 cases. Leukemia 2017;31:705–11. - PubMed
    1. Papaemmanuil E, Gerstung M, Bullinger L, Gaidzik VI, Paschka P, Roberts ND, et al. Genomic classification and prognosis in acute myeloid leukemia. N Engl J Med 2016;374:2209–21. - PMC - PubMed

Publication types