Evidence-based risk stratification of myeloid neoplasms harboring TP53 mutations
Open accessAbstract
This retrospective analysis aimed to provide evidence-based risk stratification of TP53-mutated (TP53mut) myeloid neoplasms (MNs). Of 580 MNs harboring TP53mut with variant allele frequency (VAF) ≥2%, 219 (37.8%), 194 (33.4%), 92 (15.9%), and 75 (12.9%) were classified as acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) with low blasts (MDS-LB), MDS with excess blasts (MDS-EB)-2, and -EB1 according to the revised fourth edition of the World Health Organization (WHO) classification, respectively. Hierarchical analysis identified the following 4 risk groups with distinct survival: (1) MDS-LB, (2) MDS-EB1/EB2/AML VAF <10%, (3) MDS-EB1/EB2 VAF ≥10%, and (4) AML VAF ≥10%. We next evaluated the impact of allelic status, VAF, and complex karyotype (CK). In our cohort, the significance of biallelic status was limited to MDS with <5% blasts and not for blasts 5% to 9%, as proposed by the International Consensus Classification (ICC), or 5% to 19%, as proposed by the fifth edition of the WHO (WHO-5). MDS-EB1 and -EB2 with VAF ≥10% had comparable survival (9.6 vs 7.2 months; P = .12), regardless of allelic status. Contrary to the ICC proposal, MDS-EB1/EB2 with VAF <10% and CK had poor survival compared with those without CK, comparable to MDS-EB1/EB2 with VAF ≥10% (5.6 vs 26.2 vs 6.3 months; P = .003). Survival of TP53mut AML was poor (median 3.9 months) regardless of allelic/CK status. Thus, using ICC or WHO-5 may underestimate prognosis of MDS with blasts 5% to 19% and 5% to 9%, respectively. Collectively, the hierarchical model acknowledges poor survival of 91.9% TP53mut MDS and AML compared with 36.5% and 80.7% by WHO-5 and ICC, respectively.
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WHO 2022 and ICC define biallelic/multihit mTP53 MDS as discrete entities, and both systems may significantly underrecognize this entity.
“the updated World Health Organization (WHO) 2022 criteria and the 2022 International Consensus Classification (ICC) define biallelic/multihit mTP53 MDS as discrete entities, although with heterogeneity in classification, and notably, both systems may significantly underrecognize this entity.”
From Long‐term follow‐up and combined Phase 2 results of eprenetapopt and azacitidine in patients with <i>TP53</i> mutant MDS/AML (2025) · cites this paper as [12]
The Introduction says WHO-5 and ICC recognize TP53-mutated MDS and myeloid neoplasms as distinct entities, respectively, and describes their differing criteria for biallelic or multihit MDS. The Discussion reports that WHO-5 and ICC would not classify 64% and 19%, respectively, of the study’s TP53-mutated myeloid-neoplasm cohort. Those figures concern the broader cohort, including AML, rather than showing that both systems substantially underrecognize biallelic/multihit MDS specifically. (LLM, conf=0.86)
Experimental — accuracy not yet measuredA recent study identified 92% of TP53 mutant MDS/AML patients to represent a poor risk population.
“with a recent study identifying 92% of TP53 mutant MDS/AML patients to represent a poor risk population.”
From Long‐term follow‐up and combined Phase 2 results of eprenetapopt and azacitidine in patients with <i>TP53</i> mutant MDS/AML (2025) · cites this paper as [12]
There is a strong interplay between VAF, allelic state, and cytogenetic complexity predicting outcomes in mTP53 MDS/AML.
“there is a very strong interplay between VAF, allelic state, and cytogenetic complexity strongly predicting outcomes in this molecular subset”
From Long‐term follow‐up and combined Phase 2 results of eprenetapopt and azacitidine in patients with <i>TP53</i> mutant MDS/AML (2025) · cites this paper as [12]
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Cites
Genomic classification and prognosis in acute myeloid leukemia
Papaemmanuil, E., Gerstung, M., Bullinger, L., Gaidzik, V. I., Paschka, P., Roberts, N. D., Potter, N. E., Heuser, M., Thol, F., Bolli, N., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1516192 · Cited by 4,350 · see citing works
Khoury, J. D., Solary, E., Abla, O., Akkari, Y., Alaggio, R., Apperley, J. F., Bejar, R., Berti, E., Busque, L., Chan, J. K. C., et al. (2022) · Leukemia · doi:10.1038/s41375-022-01613-1 · Cited by 4,274 · see citing works
Arber, D. A., Orazi, A., Hasserjian, R. P., Borowitz, M. J., Calvo, K. R., Kvasnicka, H.-M., Wang, S. A., Bagg, A., Barbui, T., Branford, S., et al. (2022) · Blood · doi:10.1182/blood.2022015850 · Cited by 2,945 · see citing works
Self-citationClinical and biological implications of driver mutations in myelodysplastic syndromes
Papaemmanuil, E., Gerstung, M., Malcovati, L., Tauro, S., Gundem, G., Van Loo, P., Yoon, C. J., Ellis, P., Wedge, D. C., Pellagatti, A., et al. (2013) · Blood · doi:10.1182/blood-2013-08-518886 · Cited by 1,832 · see citing works
Clinical Effect of Point Mutations in Myelodysplastic Syndromes
Bejar, R., Stevenson, K., Abdel-Wahab, O., Galili, N., Nilsson, B., Garcia-Manero, G., Kantarjian, H., Raza, A., Levine, R. L., Neuberg, D., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1013343 · Cited by 1,627 · see citing works
Landscape of genetic lesions in 944 patients with myelodysplastic syndromes
Haferlach, T., Nagata, Y., Grossmann, V, Okuno, Y., Bacher, U., Nagae, G., Schnittger, S., Sanada, M., Kon, A., Alpermann, T., et al. (2014) · Leukemia · doi:10.1038/leu.2013.336 · Cited by 1,532 · see citing works
Prognostic Mutations in Myelodysplastic Syndrome after Stem-Cell Transplantation
Lindsley, R. C., Saber, W., Mar, B. G., Redd, R., Wang, T., Haagenson, M. D., Grauman, P. V., Hu, Z.-H., Spellman, S. R., Lee, S. J., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1611604 · Cited by 776 · see citing works
Bernard, E., Nannya, Y., Hasserjian, R. P., Devlin, S. M., Tuechler, H., Medina-Martinez, J. S., Yoshizato, T., Shiozawa, Y., Saiki, R., Malcovati, L., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-1008-z · Cited by 648 · see citing works
Grob, T., Al Hinai, A. S. A., Sanders, M. A., Kavelaars, F. G., Rijken, M., Gradowska, P. L., Biemond, B. J., Breems, D. A., Maertens, J., van Marwijk Kooy, M., et al. (2022) · Blood · doi:10.1182/blood.2021014472 · Cited by 305 · see citing works
Kadia, T. M., Jain, P., Ravandi, F., Garcia‐Manero, G., Andreef, M., Takahashi, K., Borthakur, G. M., Jabbour, E. J., Konopleva, M. Y., Daver, N. G., et al. (2016) · Cancer · doi:10.1002/cncr.30203 · Cited by 261 · see citing works
for the International Working Group for MDS Molecular Prognostic Committee, Haase, D., Stevenson, K. E., Neuberg, D., Maciejewski, J. P., Nazha, A., Sekeres, M. A., Ebert, B. L., Garcia-Manero, G., Haferlach, C., et al. (2019) · Leukemia · doi:10.1038/s41375-018-0351-2 · Cited by 259 · see citing works
Sallman, D. A., Komrokji, R., Vaupel, C., Cluzeau, T., Geyer, S. M., McGraw, K. L., Al Ali, N. H., Lancet, J., McGinniss, M. J., Nahas, S., et al. (2016) · Leukemia · doi:10.1038/leu.2015.304 · Cited by 231 · see citing works
Bowen, D., Groves, M. J., Burnett, A. K., Patel, Y., Allen, C. G., Green, C. L., Gale, R. E., Hills, R. K., & Linch, D. C. (2008) · Leukemia · doi:10.1038/leu.2008.173 · Cited by 214 · see citing works
TP53 mutation defines a unique subgroup within complex karyotype de novo and therapy-related MDS/AML
Weinberg, O. K., Siddon, A. J., Madanat, Y. F., Gagan, J., Arber, D. A., Cin, P. D., Narayanan, D., Ouseph, M. M., Kurzer, J. H., & Hasserjian, R. P. (2022) · Blood Advances · doi:10.1182/bloodadvances.2021006239 · Cited by 199 · see citing works
Self-citationShort, N. J., Bravo, G. M., Hwang, H., Ning, J., Franquiz, M. J., Kanagal‐Shamanna, R., Patel, K. P., Dinardo, C. D., Ravandi, F., Garcia‐Manero, G., et al. (2020) · Blood Advances · doi:10.1182/bloodadvances.2020003120 · Cited by 181 · see citing works
The role of TP53 in acute myeloid leukemia: Challenges and opportunities
Barbosa, K., Li, S., Adams, P. D., & Deshpande, A. J. (2019) · Genes Chromosomes and Cancer · doi:10.1002/gcc.22796 · Cited by 118 · see citing works
Stengel, A., Meggendorfer, M., Walter, W., Baer, C., Nadarajah, N., Hutter, S., Kern, W., Haferlach, T., & Haferlach, C. (2023) · Blood Advances · doi:10.1182/bloodadvances.2023010312 · Cited by 53 · see citing works
Shah, M. V., Tran, E. N. H., Shah, S., Chhetri, R., Baranwal, A., Ładoń, D., Shultz, C. T., Al‐Kali, A., Brown, A. L., Chen, D., et al. (2023) · Blood Cancer Journal · doi:10.1038/s41408-023-00821-x · Cited by 48 · see citing works
Self-citationNovel scheme for defining the clinical implications of TP53 mutations in myeloid neoplasia
Bahaj, W., Kewan, T., Gurnari, C., Durmaz, A., Ponvilawan, B., Pandit, I., Kubota, Y., Ogbue, O. D., Zawit, M., Madanat, Y., et al. (2023) · Journal of Hematology & Oncology · doi:10.1186/s13045-023-01480-y · Cited by 45 · see citing works
TP53 mutation in therapy-related myeloid neoplasm defines a distinct molecular subtype
Hiwase, D., Hahn, C. N., Tran, E. N. H., Chhetri, R., Baranwal, A., Al‐Kali, A., Sharplin, K. M., Ładoń, D., Hollins, R., Greipp, P. T., et al. (2022) · Blood · doi:10.1182/blood.2022018236 · Cited by 42 · see citing works
Self-citationTP53-mutated acute myeloid leukemia: how can we improve outcomes?
Sallman, D. A., & Stahl, M. F. (2024) · Blood · doi:10.1182/blood.2024024245 · Cited by 32 · see citing works
Targeting TP53 Mutations in Myelodysplastic Syndromes
Hunter, A. M., & Sallman, D. A. (2019) · Hematology/Oncology Clinics of North America · doi:10.1016/j.hoc.2019.11.004 · Cited by 24 · see citing works
Diagnosis of TP53-mutated myeloid disease by the ICC and WHO fifth edition classifications
Hart, S. A., Lee, L. A., Seegmiller, A. C., & Mason, E. F. (2024) · Blood Advances · doi:10.1182/bloodadvances.2024014140 · Cited by 19 · see citing works
Shah, M. V., Kutyna, M., Shah, S., Tran, E. N. H., Baranwal, A., Ładoń, D., Al‐Kali, A., Brown, A. L., Chen, D., Greipp, P. T., et al. (2023) · Blood · doi:10.1182/blood-2023-187860 · Cited by 5 · see citing works
Self-citationHarrell, F., Jr. (1996) · doi:10.1002/(sici)1097-0258(19960229)15:4
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“12,14,15 Hypomethylating agents (HMA) are the standard of care for m TP53 MDS with complete remission (CR) rates at least similar to wildtype patients, although with a poor median overall survival (OS) of 12 months.”
Shah, M. V., Hung, K., Baranwal, A., Wechalekar, G., Al‐Kali, A., Toop, C. R., Greipp, P. T., Kutyna, M., Matin, A., Ładoń, D., et al. (2025) · Blood Cancer Journal · doi:10.1038/s41408-025-01290-0 · Cited by 15 · see citing works
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Bewersdorf, J. P., Mina, A. A., Stahl, M. F., & Zeidan, A. M. (2026) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-026-01141-2 · Cited by 11 · see citing works
Smith, A. C., Tsui, H., Usta, S., & Capo‐Chichi, J. (2025) · Molecular Cytogenetics · doi:10.1186/s13039-025-00718-3 · Cited by 13 · see citing works
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Georgantzinos, E., & Karantanos, T. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms262210818 · Cited by 7 · see citing works
Azevedo, R. S., Jabbour, E. J., Kantarjian, H. M., Lavu, S., Loghavi, S., Jain, N., Sasaki, K., Garris, R. S., Takahashi, K., Ravandi, F., et al. (2025) · Blood · doi:10.1182/blood.2025030498 · Cited by 7 · see citing works
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Sallman, D. A. (2025) · Blood Advances · doi:10.1182/bloodadvances.2025016336 · Cited by 5 · see citing works
Hunter, C. J., Im, A., & Shallis, R. M. (2026) · Cancers · doi:10.3390/cancers18020275 · Cited by 4 · see citing works
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Olesinski, E. A., & Bhatt, S. (2025) · Biomedicines · doi:10.3390/biomedicines13123007 · Cited by 4 · see citing works
Lee, C. H., Zhang, Y., McClure, B. J., Yong, A., Scott, H. S., & Kok, C. H. (2026) · Frontiers in Digital Health · doi:10.3389/fdgth.2026.1771531 · Cited by 3 · see citing works
Self-citationWiseman, T. J., Spooner, M., Khanna, S., Hung, K., Toop, C., Kutyna, M., Yu, J., Brown, A. L., Scott, H. S., Hahn, C. N., et al. (2025) · Blood Advances · doi:10.1182/bloodadvances.2025016086 · Cited by 2 · see citing works
Self-citationTesta, U., Castelli, G., & Pelosi, E. (2025) · Hematology Reports · doi:10.3390/hematolrep17060067 · Cited by 1 · see citing works
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Lu, X., Ma, X., Zhang, K., Zhang, S., Fangfang, W., Jiang, H., Jiang, Q., Chang, Y., Huang, X., & Zhao, X. (2026) · Biomedicines · doi:10.3390/biomedicines14010180 · Cited by 1 · see citing works
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Ng, J. Y., & Talaulikar, D. (2026) · Pathology · doi:10.1016/j.pathol.2026.03.014
Niimi, K., Yamamoto, E., Yoshida, K., Yasui, Y., & Kajiyama, H. (2026) · International Journal of Clinical Oncology · doi:10.1007/s10147-026-03073-4
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Mehta, R. S., Aljawai, Y. M., Kebriaei, P., Fingrut, W. B., Smallbone, P., Oran, B., Olson, A. L., Popat, U., Champlin, R. E., & Shpall, E. J. (2026) · JAMA Network Open · doi:10.1001/jamanetworkopen.2026.23265
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Testa, U. (2026) · Hemato · doi:10.3390/hemato7030025
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LIND, K., Dutta, S., Cosenza, M. R., Eder, T., Foßelteder, J., Pabst, G., Schöll, W., Prokesch, A., Auner, H. W., Wölfler, A., et al. (2026) · Leukemia · doi:10.1038/s41375-026-03106-x
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Sun, Y., Liu, D., Dou, L., & 胡亮钉 (2026) · Cancer Pathogenesis and Therapy · doi:10.1016/j.cpt.2026.10.004
- Authors
- Shah, M. V., Hung, K., Baranwal, A., Kutyna, M. M., Al-Kali, A., Toop, C., Greipp, P., Brown, A., Shah, S., Khanna, S., Ladon, D., Gannamani, V., Chen, D., Begna, K., Price, Z. K., Rud, D., Litzow, M. R., Hogan, W. J., Bardy, P., Badar, T., Kumar, S., Yeung, D. T., Patnaik, M. M., Foran, J. M., He, R., Gangat, N., Scott, H. S., Arana Yi, C. Y., Alkhateeb, H., Mangaonkar, A. A., Thomas, D., Hahn, C. N., Orazi, A., Arber, D. A., Kok, C. H., Tefferi, A., & Hiwase, D.
- Affiliations
- Mayo Clinic (US)
- Royal Adelaide Hospital (AU)
- 1Division of Hematology, Mayo Clinic, Rochester, MN
- South Australia Pathology (AU)
- 7Department of Genetic and Molecular Pathogy, SA Pathology, Adelaide, SA, Australia
- South Australian Health and Medical Research Institute (AU)
- Mayo Clinic in Florida (US)
- Mayo Clinic in Arizona (US)
- 8Department of Hematology/Oncology, Mayo Clinic, Jacksonville, FL
- 2Department of Haematology, Royal Adelaide Hospital, Central Adelaide Local Health Network, Adelaide, SA, Australia
- Texas Tech University Health Sciences Center (US)
- University of Chicago (US)
- Corresponding author
- Shah, Mithun Vinod
- Hiwase, Devendra
- ORCID
- Shah, Mithun Vinod
- Hung, Kevin
- Baranwal, Anmol
- Kutyna, Monika M.
- Al-Kali, Aref
- Toop, Carla
- Greipp, Patricia
- Brown, Anna
- Chen, Dong
- Begna, Kebede
- Price, Zoe K.
- Litzow, Mark R.
- Hogan, William J.
- Badar, Talha
- Kumar, Sharad
- Yeung, David T.
- Patnaik, Mrinal M.
- Foran, James M.
- He, Rong
- Gangat, Naseema
- Scott, Hamish S.
- Arana Yi, Cecilia Y.
- Alkhateeb, Hassan
- Mangaonkar, Abhishek A.
- Hahn, Christopher N.
- Orazi, Attilio
- Arber, Daniel A.
- Kok, Chung Hoow
- Tefferi, Ayalew
- Hiwase, Devendra
- Venue
- Blood Advances
- Publisher
- American Society of Hematology
- Published
- 2025-07-08
- Volume
- 9
- Issue
- 13
- Pages
- 3370-3380
- ISSN
- 2473-9529 (ISSN-L)
- 2473-9537
- PMC
- PMC12277823
- OpenAlex
- W4408475480
- Cited by
- 23
- References
- 25
- Citations by year
- 2026: 13 · 2025: 10
- FWCI
- 16.89
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Blood Advances (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion, cc-by-nc-nd)
- Funders
- Cancer Australia
- Medical Research Council
- National Health and Medical Research Council
- Medical Research Future Fund
- Topics
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Health Sciences › Medicine › Hematology › Chronic Myeloid Leukemia Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
- Keywords
- TP53 mutation, myeloid neoplasms, risk stratification, variant allele frequency, acute myeloid leukemia, complex karyotype, International Consensus Classification, WHO classification, survival, prognostic factors, International Prognostic Scoring System
- MeSH terms
- Adult, Aged, Aged, 80 and over, Female, Gene Frequency, Humans, Male, Middle Aged, Mutation, Myelodysplastic Syndromes, Prognosis, Retrospective Studies, Leukemia, Myeloid, Acute, Tumor Suppressor Protein p53, Risk Assessment
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