Potential Use of WT1 as a Diagnostic and Therapeutic Marker of Acute Myeloid Leukemia: A Review
Keywords:
acute myeloid leukemia, biomarker, Measurable residual disease, Molecular diagnostics, Precision hematology, WT1 gene
Abstract
Acute myeloid leukemia (AML) is a heterogeneous malignancy characterized by uncontrolled proliferation and impaired hematopoietic differentiation of myeloid lineage with rapid disease progression. Among the various biomarkers studied, Wilms’ tumor 1 (WT1) is a widely expressed gene in AML, making it an attractive biomarker candidate for diagnosis and minimal residual disease (MRD) monitoring. This review evaluates the potential of WT1 as an effective diagnostic biomarker and the current detection methods, highlighting the advantages and limitations of the current gold standard, RT-qPCR, and exploring potential alternative approaches, such as ELISA and antibody-based flow cytometry, for its clinical applicability. Using public gene datasets, bioinformatic analysis further supports WT1’s overexpression in AML, though with varying levels across subtypes, suggesting its potential as part of a multimodal diagnostic plan rather than a standalone marker. Beyond diagnostics, WT1 is also a promising therapeutic target, with peptide and dendritic cell vaccines, as well as TCR-engineered T cells, demonstrating encouraging clinical outcomes. Next-generation strategies, including CAR-T cells, bispecific T-cell engagers, and mRNA vaccines, are advancing preclinical and early clinical studies. Together, these findings highlight WT1 as both a biomarker and a therapeutic target, with future integration into precision medicine likely to improve AML detection, risk stratification, and treatment.
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References
Abaza, Y., & Zeidan, A. M. (2022). Immune Checkpoint Inhibition in Acute Myeloid Leukemia and Myelodysplastic Syndromes. Cells, 11(14), 2249. https://doi.org/10.3390/cells11142249
Alikian, M., Whale, A. S., Akiki, S., Piechocki, K., Torrado, C., Myint, T., Cowen, S., Griffiths, M., Reid, A. G., Apperley, J., White, H., Huggett, J. F., & Foroni, L. (2016). RT-qPCR and RT-Digital PCR: A Comparison of Different Platforms for the Evaluation of Residual Disease in Chronic Myeloid Leukemia. Clinical Chemistry, 63(2), 525–531. https://doi.org/10.1373/clinchem.2016.262824
Ally, F., & Chen, X. (2024). Acute Myeloid Leukemia: Diagnosis and Evaluation by Flow Cytometry. Cancers, 16(22), 3855–3855. https://doi.org/10.3390/cancers16223855
Alzaaqi, S., Naka, N., Hamada, K., Hosen, N., Kanegae, M., Outani, H., Adachi, M., Imanishi, R., Morii, E., Iwai, M., Nakata, J., Fujiki, F., Morimoto, S., Nakajima, H., Nishida, S., Tsuboi, A., Oka, Y., Sugiyama, H., & Oji, Y. (2022). WT1 epitope‑specific IgG and IgM antibodies for immune‑monitoring in patients with advanced sarcoma treated with a WT1 peptide cancer vaccine. Oncology Letters, 23(2). https://doi.org/10.3892/ol.2022.13184
Anguille, S., Van de Velde, A. L., Smits, E. L., Van Tendeloo, V. F., Juliusson, G., Cools, N., Nijs, G., Stein, B., Lion, E., Van Driessche, A., Vandenbosch, I., Verlinden, A., Gadisseur, A. P., Schroyens, W. A., Muylle, L., Vermeulen, K., Maes, M.-B., Deiteren, K., Malfait, R., & Gostick, E. (2017). Dendritic cell vaccination as postremission treatment to prevent or delay relapse in acute myeloid leukemia. Blood, 130(15), 1713–1721. https://doi.org/10.1182/blood-2017-04-780155
Antoniou, E., Hoffmeister, L. M., Neuhoff, N. V., Reinhardt, D., Schneider, M., & Sendker, S. (2024). Significance of RT-qPCR-Based Measurable Residual Disease for Optimizing the Treatment of Pediatric Acute Myeloid Leukemia. Blood, 144(Supplement 1), 228–228. https://doi.org/10.1182/blood-2024-208718
Brunangelo Falini, & Dillon, R. (2023). Criteria for Diagnosis and Molecular Monitoring of NPM1-Mutated AML. Blood Cancer Discovery, OF1–OF12. https://doi.org/10.1158/2643-3230.bcd-23-0144
Chandrashekar, D. S., Bashel, B., Balasubramanya, S. A. H., Creighton, C. J., Ponce-Rodriguez, I., Chakravarthi, B. V. S. K., & Varambally, S. (2017). UALCAN: A Portal for Facilitating Tumor Subgroup Gene Expression and Survival Analyses. Neoplasia, 19(8), 649–658. https://doi.org/10.1016/j.neo.2017.05.002
Chandrashekar, D. S., Karthikeyan, S. K., Korla, P. K., Patel, H., Shovon, A. R., Athar, M., Netto, G. J., Qin, Z. S., Kumar, S., Manne, U., Creighton, C. J., & Varambally, S. (2022). UALCAN: An update to the integrated cancer data analysis platform. Neoplasia, 25, 18–27. https://doi.org/10.1016/j.neo.2022.01.001
Chapuis, A. G., Desmarais, C., Emerson, R., Schmitt, T. M., Shibuya, K. C., Lai, I. P., Wagener, F., Chou, J., Roberts, I. M., Coffey, D. G., Warren, E. H., Robins, H., Greenberg, P. D., & Yee, C. (2017). Tracking the fate and origin of clinically relevant adoptively transferred CD8+T cells in vivo. Science Immunology, 2(8), eaal2568. https://doi.org/10.1126/sciimmunol.aal2568
Chapuis, A. G., Egan, D. N., Bar, M., Schmitt, T. M., McAfee, M. S., Paulson, K. G., Voillet, V., Gottardo, R., Ragnarsson, G. B., Bleakley, M., Yeung, C. C., Muhlhauser, P., Nguyen, H. N., Kropp, L. A., Castelli, L., Wagener, F., Hunter, D., Lindberg, M., Cohen, K., & Seese, A. (2019). T cell receptor gene therapy targeting WT1 prevents acute myeloid leukemia relapse post-transplant. Nature Medicine, 25(7), 1064–1072. https://doi.org/10.1038/s41591-019-0472-9
Dao, T., Dmitry Pankov, Scott, A., Korontsvit, T., Victoriya Zakhaleva, Xu, Y., Xiang, J., Su, Y., Guerreiro, M., Veomett, N., Dubrovsky, L., Curcio, M., Ekaterina Doubrovina, Ponomarev, V., Liu, C., O’Reilly, R. J., & Scheinberg, D. A. (2015). Therapeutic bispecific T-cell engager antibody targeting the intracellular oncoprotein WT1. Nature Biotechnology, 33(10), 1079–1086. https://doi.org/10.1038/nbt.3349
Daver, N., Boddu, P., Garcia-Manero, G., Yadav, S. S., Sharma, P., Allison, J., & Kantarjian, H. (2018). Hypomethylating agents in combination with immune checkpoint inhibitors in acute myeloid leukemia and myelodysplastic syndromes. Leukemia, 32(5), 1094–1105. https://doi.org/10.1038/s41375-018-0070-8
Daver, N., Schlenk, R. F., Russell, N. H., & Levis, M. J. (2019). Targeting FLT3 mutations in AML: review of current knowledge and evidence. Leukemia, 33(2), 299–312. https://doi.org/10.1038/s41375-018-0357-9
FoBinf. (2024). Normal human v2 with AMLs: WT1 expression. Fobinf.com. https://www.fobinf.com/?gene=WT1&dataset=normal_human_v2_with_AMLs
Fu, Q., Zhao, X., Hu, J., Jiao, Y., Yan, Y., Pan, X., Wang, X., & Jiao, F. (2025). mRNA vaccines in the context of cancer treatment: from concept to application. Journal of Translational Medicine, 23(1). https://doi.org/10.1186/s12967-024-06033-6
Gielis, S., Flumens, D., van der Heijden, S., Versteven, M., De Reu, H., Bartholomeus, E., Schippers, J., Campillo-Davo, D., Berneman, Z. N., Anguille, S., Smits, E., Ogunjimi, B., Lion, E., Laukens, K., & Meysman, P. (2024). Analysis of Wilms’ tumor protein 1 specific TCR repertoire in AML patients uncovers higher diversity in patients in remission than in relapsed. Annals of Hematology. https://doi.org/10.1007/s00277-024-05919-1
Giudice, V., Gorrese, M., Vitolo, R., Bertolini, A., Marcucci, R., Serio, B., Guariglia, R., Ferrara, I., Pepe, R., D’Alto, F., Izzo, B., Pedicini, A., Montuori, N., Langella, M., & Selleri, C. (2021). WT1 Expression Levels Combined with Flow Cytometry Blast Counts for Risk Stratification of Acute Myeloid Leukemia and Myelodysplastic Syndromes. Biomedicines, 9(4), 387–387. https://doi.org/10.3390/biomedicines9040387
GTEx Consortium, GTEx Portal, online: https://gtexportal.org/home/.
Guo, Z., Sun, L., Xia, H., Tian, S., Liu, M., Hou, J., Li, J., Lin, H., & Du, G. (2022). Shikonin as a WT1 Inhibitor Promotes Promyeloid Leukemia Cell Differentiation. Molecules, 27(23), 8264–8264. https://doi.org/10.3390/molecules27238264
Hastie, N. D. (2017). Wilms’ tumour 1 (WT1) in development, homeostasis and disease. Development, 144(16), 2862–2872. https://doi.org/10.1242/dev.153163
Ivey, A., Hills, R. K., Simpson, M. A., Jovanovic, J. V., Gilkes, A., Grech, A., Patel, Y., Bhudia, N., Farah, H., Mason, J., Wall, K., Akiki, S., Griffiths, M., Solomon, E., McCaughan, F., Linch, D. C., Gale, R. E., Vyas, P., Freeman, S. D., & Russell, N. (2016). Assessment of Minimal Residual Disease in Standard-Risk AML. New England Journal of Medicine, 374(5), 422–433. https://doi.org/10.1056/nejmoa1507471
Kang, S., Li, Y., Qiao, J., Meng, X., He, Z., Gao, X., & Yu, L. (2022). Antigen-Specific TCR-T Cells for Acute Myeloid Leukemia: State of the Art and Challenges. Frontiers in Oncology, 12. https://doi.org/10.3389/fonc.2022.787108
Kreutmair, S., Pfeifer, D., Waterhouse, M., Takács, F., Graessel, L., Döhner, K., Duyster, J., Illert, A. L., Frey, A.-V., Schmitt, M., & Lübbert, M. (2022). First-in-human study of WT1 recombinant protein vaccination in elderly patients with AML in remission: a single-center experience. Cancer Immunology, Immunotherapy, 71(12), 2913–2928. https://doi.org/10.1007/s00262-022-03202-8
Lazzarotto, D., & Candoni, A. (2022). The Role of Wilms’ Tumor Gene (WT1) Expression as a Marker of Minimal Residual Disease in Acute Myeloid Leukemia. Journal of Clinical Medicine, 11(12), 3306. https://doi.org/10.3390/jcm11123306
Malagola, M., Skert, C., Borlenghi, E., Chiarini, M., Cattaneo, C., Morello, E., Cancelli, V., Federica Cattina, Cerqui, E., Pagani, C., Passi, A., Rossella Ribolla, Bernardi, S., Giustini, V., Lamorgese, C., Ruggeri, G., Imberti, L., Caimi, L., Russo, D., & Rossi, G. (2015). Postremission sequential monitoring of minimal residual disease by WT 1 Q‐ PCR and multiparametric flow cytometry assessment predicts relapse and may help to address risk‐adapted therapy in acute myeloid leukemia patients. Cancer Medicine, 5(2), 265–274. https://doi.org/10.1002/cam4.593
Maslak, P. G., Dao, T., Bernal, Y., Chanel, S. M., Zhang, R., Frattini, M., Rosenblat, T., Jurcic, J. G., Brentjens, R. J., Arcila, M. E., Rampal, R., Park, J. H., Douer, D., Katz, L., Sarlis, N., Tallman, M. S., & Scheinberg, D. A. (2018). Phase 2 trial of a multivalent WT1 peptide vaccine (galinpepimut-S) in acute myeloid leukemia. Blood Advances, 2(3), 224–234. https://doi.org/10.1182/bloodadvances.2017014175
Menssen, H. D., Renkl, H. J., Rodeck, U., Maurer, J., Notter, M., Schwartz, S., Reinhardt, R., & Thiel, E. (1995). Presence of Wilms’ tumor gene (wt1) transcripts and the WT1 nuclear protein in the majority of human acute leukemias. Leukemia, 9(6), 1060–1067. https://pubmed.ncbi.nlm.nih.gov/7596170/
Miwa, H., Beran, M., & Saunders, G. F. (1992). Expression of the Wilms’ tumor gene (WT1) in human leukemias. Leukemia, 6(5), 405–409. https://pubmed.ncbi.nlm.nih.gov/1317488/
Musalli, M. G., Hassan, M. A., Sheikh, R. A., Kalantan, A. A., Halwani, M. A., Zeyadi, M., Hosawi, S., & Alhosin, M. (2019). Thymoquinone induces cell proliferation inhibition and apoptosis in acute myeloid leukemia cells: role of apoptosis-related WT1 and BCL2 genes. European Journal of Cell Science, 02–09. https://doi.org/10.34154/2019-ejcs-0101-02-09/euraass
Nian, Q., Lin, Y., Zeng, J., Zhang, Y., & Liu, R. (2025). Multifaceted functions of the Wilms tumor 1 protein: From its expression in various malignancies to targeted therapy. Translational Oncology, 52(2011), 102237. https://doi.org/10.1016/j.tranon.2024.102237
Nishikawa, T., Wojciak, J. M., Dyson, H. J., & Wright, P. E. (2020). RNA Binding by the KTS Splice Variants of Wilms’ Tumor Suppressor Protein WT1. Biochemistry, 59(40), 3889–3901. https://doi.org/10.1021/acs.biochem.0c00602
Oji, Y. (2024). Enzyme-Linked Immunosorbent Assay for Antibodies Against the Tumor-Associated Antigen-Derived Cytotoxic T-Lymphocyte Epitope. Methods in Molecular Biology, 217–223. https://doi.org/10.1007/978-1-0716-3914-6_17
Oji, Y., Hashimoto, N., Tsuboi, A., Murakami, Y., Iwai, M., Kagawa, N., Chiba, Y., Izumoto, S., Elisseeva, O., Ichinohasama, R., Sakamoto, J., Morita, S., Nakajima, H., Takashima, S., Nakae, Y., Nakata, J., Kawakami, M., Nishida, S., Hosen, N., & Fujiki, F. (2016). Association of WT1 IgG antibody against WT1 peptide with prolonged survival in glioblastoma multiforme patients vaccinated with WT1 peptide. International Journal of Cancer, 139(6), 1391–1401. https://doi.org/10.1002/ijc.30182
Palomares, F., Pina, A., Hala Dakhaoui, Leiva-Castro, C., Munera-Rodriguez, A. M., Cejudo-Guillen, M., Granados, B., Alba, G., Santa-Maria, C., Sobrino, F., & Lopez-Enriquez, S. (2024). Dendritic Cells as a Therapeutic Strategy in Acute Myeloid Leukemia: Vaccines. Vaccines, 12(2), 165–165. https://doi.org/10.3390/vaccines12020165
Pan, X., Gao, M., Sun, Y., Zhou, Y., Wang, K., Wang, Y., Xu, L., Zhang, X., Huang, X., & Zhao, X. (2022). Significance of WT1 and multiparameter flow cytometry assessment in patients with chronic myelomonocytic leukemia receiving allogeneic hematopoietic stem cell transplantation. International Journal of Laboratory Hematology, 44(3), 510–517. https://doi.org/10.1111/ijlh.13788
Panuzzo, C., Jovanovski, A., Ali, M. S., Cilloni, D., & Pergolizzi, B. (2022). Revealing the Mysteries of Acute Myeloid Leukemia: From Quantitative PCR through Next-Generation Sequencing and Systemic Metabolomic Profiling. Journal of Clinical Medicine, 11(3), 483. https://doi.org/10.3390/jcm11030483
Rafiq, S., Purdon, T. J., Daniyan, A. F., Koneru, M., Dao, T., Liu, C., Scheinberg, D. A., & Brentjens, R. J. (2016). Optimized T-cell receptor-mimic chimeric antigen receptor T cells directed toward the intracellular Wilms Tumor 1 antigen. Leukemia, 31(8), 1788–1797. https://doi.org/10.1038/leu.2016.373
Rampal, R., & Figueroa, M. E. (2016). Wilms tumor 1 mutations in the pathogenesis of acute myeloid leukemia. Haematologica, 101(6), 672–679. https://doi.org/10.3324/haematol.2015.141796
Romanova, E. I., Zubritskiy, Anatoliy V, Lioznova, A. V., Ogunleye, A. J., Golotin, Vasily A, Guts, A. A., Lennartsson, A., Demidov, Oleg N, & Medvedeva, Yulia A. (2022). RUNX1/CEBPA Mutation in Acute Myeloid Leukemia Promotes Hypermethylation and Indicates for Demethylation Therapy. International Journal of Molecular Sciences, 23(19), 11413. https://doi.org/10.3390/ijms231911413
Ruggiero, E., Liu, D., Prodeus, A., Becker, A. M., Foisey, M., Balwani, I., Dutta, I., Zhang, Q., Arredouani, S. M., McKee, M., Ciceri, F., Sepp-Lorenzino, L., Bonini, C., & Schultes, B. C. (2020). NTLA5001, a T Cell Product Candidate with CRISPR-Based Targeted Insertion of a High-Avidity, Natural, WT1-Specific TCR, Shows Efficacy in In Vivo Models of AML and ALL. Blood, 136(Supplement 1), 32–33. https://doi.org/10.1182/blood-2020-143119
Schuurhuis, G. J., Heuser, M., Freeman, S., Béné, M.-C., Buccisano, F., Cloos, J., Grimwade, D., Haferlach, T., Hills, R. K., Hourigan, C. S., Jorgensen, J. L., Kern, W., Lacombe, F., Maurillo, L., Preudhomme, C., van der Reijden, B. A., Thiede, C., Venditti, A., Vyas, P., & Wood, B. L. (2018). Minimal/measurable residual disease in AML: a consensus document from the European LeukemiaNet MRD Working Party. Blood, 131(12), 1275–1291. https://doi.org/10.1182/blood-2017-09-801498
Tawara, I., Kageyama, S., Miyahara, Y., Fujiwara, H., Nishida, T., Yoshiki Akatsuka, Ikeda, H., Tanimoto, K., Seitaro Terakura, Murata, M., Inaguma, Y., Masahiro Masuya, Inoue, N., Tomohide Kidokoro, Okamoto, S., Daisuke Tomura, Hideto Chono, Ikuei Nukaya, Junichi Mineno, & Tomoki Naoe. (2017). Safety and persistence of WT1-specific T-cell receptor gene−transduced lymphocytes in patients with AML and MDS. Blood, 130(18), 1985–1994. https://doi.org/10.1182/blood-2017-06-791202
Tian, Z., Liu, M., Zhang, Y., & Wang, X. (2021). Bispecific T cell engagers: an emerging therapy for management of hematologic malignancies. Journal of Hematology & Oncology, 14(1). https://doi.org/10.1186/s13045-021-01084-4
Vakiti, A., & Mewawalla, P. (2024). Cancer, Acute Myeloid Leukemia (AML, Erythroid Leukemia, Myelodysplasia-Related Leukemia, BCR-ABL Chronic Leukemia). Nih.gov; StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK507875/
van de Loosdrecht, A. A., van Wetering, S., Santegoets, S. J. A. M., Singh, S. K., Eeltink, C. M., den Hartog, Y., Koppes, M., Kaspers, J., Ossenkoppele, G. J., Kruisbeek, A. M., & de Gruijl, T. D. (2018). A novel allogeneic off-the-shelf dendritic cell vaccine for post-remission treatment of elderly patients with acute myeloid leukemia. Cancer Immunology, Immunotherapy: CII, 67(10), 1505–1518. https://doi.org/10.1007/s00262-018-2198-9
Yang, L., Han, Y., Saurez Saiz, F., & Minden, M. D. (2007). A tumor suppressor and oncogene: the WT1 story. Leukemia, 21(5), 868–876. https://doi.org/10.1038/sj.leu.2404624
Zhang, R., Yang, J. Y., Sun, H. Q., Jia, H., Liao, J., Shi, Y. J., & Li, G. (2015). Comparison of minimal residual disease (MRD) monitoring by WT1 quantification between childhood acute myeloid leukemia and acute lymphoblastic leukemia. European Review for Medical and Pharmacological Sciences, 19(14), 2679–2688. https://pubmed.ncbi.nlm.nih.gov/26221900/
Zhou, B., Jin, X., Jin, W., Huang, X., Wu, Y., Li, H., Zhu, W., Qin, X., Ye, H., & Gao, S. (2020). WT1 facilitates the self-renewal of leukemia-initiating cells through the upregulation of BCL2L2: WT1-BCL2L2 axis as a new acute myeloid leukemia therapy target. Journal of Translational Medicine, 18(1). https://doi.org/10.1186/s12967-020-02384-y
Zhou, Y., Huang, G., Cai, X., Liu, Y., Qian, B., & Li, D. (2024). Global, regional, and national burden of acute myeloid leukemia, 1990–2021: a systematic analysis for the global burden of disease study 2021. Biomarker Research, 12(1). https://doi.org/10.1186/s40364-024-00649-y
Alikian, M., Whale, A. S., Akiki, S., Piechocki, K., Torrado, C., Myint, T., Cowen, S., Griffiths, M., Reid, A. G., Apperley, J., White, H., Huggett, J. F., & Foroni, L. (2016). RT-qPCR and RT-Digital PCR: A Comparison of Different Platforms for the Evaluation of Residual Disease in Chronic Myeloid Leukemia. Clinical Chemistry, 63(2), 525–531. https://doi.org/10.1373/clinchem.2016.262824
Ally, F., & Chen, X. (2024). Acute Myeloid Leukemia: Diagnosis and Evaluation by Flow Cytometry. Cancers, 16(22), 3855–3855. https://doi.org/10.3390/cancers16223855
Alzaaqi, S., Naka, N., Hamada, K., Hosen, N., Kanegae, M., Outani, H., Adachi, M., Imanishi, R., Morii, E., Iwai, M., Nakata, J., Fujiki, F., Morimoto, S., Nakajima, H., Nishida, S., Tsuboi, A., Oka, Y., Sugiyama, H., & Oji, Y. (2022). WT1 epitope‑specific IgG and IgM antibodies for immune‑monitoring in patients with advanced sarcoma treated with a WT1 peptide cancer vaccine. Oncology Letters, 23(2). https://doi.org/10.3892/ol.2022.13184
Anguille, S., Van de Velde, A. L., Smits, E. L., Van Tendeloo, V. F., Juliusson, G., Cools, N., Nijs, G., Stein, B., Lion, E., Van Driessche, A., Vandenbosch, I., Verlinden, A., Gadisseur, A. P., Schroyens, W. A., Muylle, L., Vermeulen, K., Maes, M.-B., Deiteren, K., Malfait, R., & Gostick, E. (2017). Dendritic cell vaccination as postremission treatment to prevent or delay relapse in acute myeloid leukemia. Blood, 130(15), 1713–1721. https://doi.org/10.1182/blood-2017-04-780155
Antoniou, E., Hoffmeister, L. M., Neuhoff, N. V., Reinhardt, D., Schneider, M., & Sendker, S. (2024). Significance of RT-qPCR-Based Measurable Residual Disease for Optimizing the Treatment of Pediatric Acute Myeloid Leukemia. Blood, 144(Supplement 1), 228–228. https://doi.org/10.1182/blood-2024-208718
Brunangelo Falini, & Dillon, R. (2023). Criteria for Diagnosis and Molecular Monitoring of NPM1-Mutated AML. Blood Cancer Discovery, OF1–OF12. https://doi.org/10.1158/2643-3230.bcd-23-0144
Chandrashekar, D. S., Bashel, B., Balasubramanya, S. A. H., Creighton, C. J., Ponce-Rodriguez, I., Chakravarthi, B. V. S. K., & Varambally, S. (2017). UALCAN: A Portal for Facilitating Tumor Subgroup Gene Expression and Survival Analyses. Neoplasia, 19(8), 649–658. https://doi.org/10.1016/j.neo.2017.05.002
Chandrashekar, D. S., Karthikeyan, S. K., Korla, P. K., Patel, H., Shovon, A. R., Athar, M., Netto, G. J., Qin, Z. S., Kumar, S., Manne, U., Creighton, C. J., & Varambally, S. (2022). UALCAN: An update to the integrated cancer data analysis platform. Neoplasia, 25, 18–27. https://doi.org/10.1016/j.neo.2022.01.001
Chapuis, A. G., Desmarais, C., Emerson, R., Schmitt, T. M., Shibuya, K. C., Lai, I. P., Wagener, F., Chou, J., Roberts, I. M., Coffey, D. G., Warren, E. H., Robins, H., Greenberg, P. D., & Yee, C. (2017). Tracking the fate and origin of clinically relevant adoptively transferred CD8+T cells in vivo. Science Immunology, 2(8), eaal2568. https://doi.org/10.1126/sciimmunol.aal2568
Chapuis, A. G., Egan, D. N., Bar, M., Schmitt, T. M., McAfee, M. S., Paulson, K. G., Voillet, V., Gottardo, R., Ragnarsson, G. B., Bleakley, M., Yeung, C. C., Muhlhauser, P., Nguyen, H. N., Kropp, L. A., Castelli, L., Wagener, F., Hunter, D., Lindberg, M., Cohen, K., & Seese, A. (2019). T cell receptor gene therapy targeting WT1 prevents acute myeloid leukemia relapse post-transplant. Nature Medicine, 25(7), 1064–1072. https://doi.org/10.1038/s41591-019-0472-9
Dao, T., Dmitry Pankov, Scott, A., Korontsvit, T., Victoriya Zakhaleva, Xu, Y., Xiang, J., Su, Y., Guerreiro, M., Veomett, N., Dubrovsky, L., Curcio, M., Ekaterina Doubrovina, Ponomarev, V., Liu, C., O’Reilly, R. J., & Scheinberg, D. A. (2015). Therapeutic bispecific T-cell engager antibody targeting the intracellular oncoprotein WT1. Nature Biotechnology, 33(10), 1079–1086. https://doi.org/10.1038/nbt.3349
Daver, N., Boddu, P., Garcia-Manero, G., Yadav, S. S., Sharma, P., Allison, J., & Kantarjian, H. (2018). Hypomethylating agents in combination with immune checkpoint inhibitors in acute myeloid leukemia and myelodysplastic syndromes. Leukemia, 32(5), 1094–1105. https://doi.org/10.1038/s41375-018-0070-8
Daver, N., Schlenk, R. F., Russell, N. H., & Levis, M. J. (2019). Targeting FLT3 mutations in AML: review of current knowledge and evidence. Leukemia, 33(2), 299–312. https://doi.org/10.1038/s41375-018-0357-9
FoBinf. (2024). Normal human v2 with AMLs: WT1 expression. Fobinf.com. https://www.fobinf.com/?gene=WT1&dataset=normal_human_v2_with_AMLs
Fu, Q., Zhao, X., Hu, J., Jiao, Y., Yan, Y., Pan, X., Wang, X., & Jiao, F. (2025). mRNA vaccines in the context of cancer treatment: from concept to application. Journal of Translational Medicine, 23(1). https://doi.org/10.1186/s12967-024-06033-6
Gielis, S., Flumens, D., van der Heijden, S., Versteven, M., De Reu, H., Bartholomeus, E., Schippers, J., Campillo-Davo, D., Berneman, Z. N., Anguille, S., Smits, E., Ogunjimi, B., Lion, E., Laukens, K., & Meysman, P. (2024). Analysis of Wilms’ tumor protein 1 specific TCR repertoire in AML patients uncovers higher diversity in patients in remission than in relapsed. Annals of Hematology. https://doi.org/10.1007/s00277-024-05919-1
Giudice, V., Gorrese, M., Vitolo, R., Bertolini, A., Marcucci, R., Serio, B., Guariglia, R., Ferrara, I., Pepe, R., D’Alto, F., Izzo, B., Pedicini, A., Montuori, N., Langella, M., & Selleri, C. (2021). WT1 Expression Levels Combined with Flow Cytometry Blast Counts for Risk Stratification of Acute Myeloid Leukemia and Myelodysplastic Syndromes. Biomedicines, 9(4), 387–387. https://doi.org/10.3390/biomedicines9040387
GTEx Consortium, GTEx Portal, online: https://gtexportal.org/home/.
Guo, Z., Sun, L., Xia, H., Tian, S., Liu, M., Hou, J., Li, J., Lin, H., & Du, G. (2022). Shikonin as a WT1 Inhibitor Promotes Promyeloid Leukemia Cell Differentiation. Molecules, 27(23), 8264–8264. https://doi.org/10.3390/molecules27238264
Hastie, N. D. (2017). Wilms’ tumour 1 (WT1) in development, homeostasis and disease. Development, 144(16), 2862–2872. https://doi.org/10.1242/dev.153163
Ivey, A., Hills, R. K., Simpson, M. A., Jovanovic, J. V., Gilkes, A., Grech, A., Patel, Y., Bhudia, N., Farah, H., Mason, J., Wall, K., Akiki, S., Griffiths, M., Solomon, E., McCaughan, F., Linch, D. C., Gale, R. E., Vyas, P., Freeman, S. D., & Russell, N. (2016). Assessment of Minimal Residual Disease in Standard-Risk AML. New England Journal of Medicine, 374(5), 422–433. https://doi.org/10.1056/nejmoa1507471
Kang, S., Li, Y., Qiao, J., Meng, X., He, Z., Gao, X., & Yu, L. (2022). Antigen-Specific TCR-T Cells for Acute Myeloid Leukemia: State of the Art and Challenges. Frontiers in Oncology, 12. https://doi.org/10.3389/fonc.2022.787108
Kreutmair, S., Pfeifer, D., Waterhouse, M., Takács, F., Graessel, L., Döhner, K., Duyster, J., Illert, A. L., Frey, A.-V., Schmitt, M., & Lübbert, M. (2022). First-in-human study of WT1 recombinant protein vaccination in elderly patients with AML in remission: a single-center experience. Cancer Immunology, Immunotherapy, 71(12), 2913–2928. https://doi.org/10.1007/s00262-022-03202-8
Lazzarotto, D., & Candoni, A. (2022). The Role of Wilms’ Tumor Gene (WT1) Expression as a Marker of Minimal Residual Disease in Acute Myeloid Leukemia. Journal of Clinical Medicine, 11(12), 3306. https://doi.org/10.3390/jcm11123306
Malagola, M., Skert, C., Borlenghi, E., Chiarini, M., Cattaneo, C., Morello, E., Cancelli, V., Federica Cattina, Cerqui, E., Pagani, C., Passi, A., Rossella Ribolla, Bernardi, S., Giustini, V., Lamorgese, C., Ruggeri, G., Imberti, L., Caimi, L., Russo, D., & Rossi, G. (2015). Postremission sequential monitoring of minimal residual disease by WT 1 Q‐ PCR and multiparametric flow cytometry assessment predicts relapse and may help to address risk‐adapted therapy in acute myeloid leukemia patients. Cancer Medicine, 5(2), 265–274. https://doi.org/10.1002/cam4.593
Maslak, P. G., Dao, T., Bernal, Y., Chanel, S. M., Zhang, R., Frattini, M., Rosenblat, T., Jurcic, J. G., Brentjens, R. J., Arcila, M. E., Rampal, R., Park, J. H., Douer, D., Katz, L., Sarlis, N., Tallman, M. S., & Scheinberg, D. A. (2018). Phase 2 trial of a multivalent WT1 peptide vaccine (galinpepimut-S) in acute myeloid leukemia. Blood Advances, 2(3), 224–234. https://doi.org/10.1182/bloodadvances.2017014175
Menssen, H. D., Renkl, H. J., Rodeck, U., Maurer, J., Notter, M., Schwartz, S., Reinhardt, R., & Thiel, E. (1995). Presence of Wilms’ tumor gene (wt1) transcripts and the WT1 nuclear protein in the majority of human acute leukemias. Leukemia, 9(6), 1060–1067. https://pubmed.ncbi.nlm.nih.gov/7596170/
Miwa, H., Beran, M., & Saunders, G. F. (1992). Expression of the Wilms’ tumor gene (WT1) in human leukemias. Leukemia, 6(5), 405–409. https://pubmed.ncbi.nlm.nih.gov/1317488/
Musalli, M. G., Hassan, M. A., Sheikh, R. A., Kalantan, A. A., Halwani, M. A., Zeyadi, M., Hosawi, S., & Alhosin, M. (2019). Thymoquinone induces cell proliferation inhibition and apoptosis in acute myeloid leukemia cells: role of apoptosis-related WT1 and BCL2 genes. European Journal of Cell Science, 02–09. https://doi.org/10.34154/2019-ejcs-0101-02-09/euraass
Nian, Q., Lin, Y., Zeng, J., Zhang, Y., & Liu, R. (2025). Multifaceted functions of the Wilms tumor 1 protein: From its expression in various malignancies to targeted therapy. Translational Oncology, 52(2011), 102237. https://doi.org/10.1016/j.tranon.2024.102237
Nishikawa, T., Wojciak, J. M., Dyson, H. J., & Wright, P. E. (2020). RNA Binding by the KTS Splice Variants of Wilms’ Tumor Suppressor Protein WT1. Biochemistry, 59(40), 3889–3901. https://doi.org/10.1021/acs.biochem.0c00602
Oji, Y. (2024). Enzyme-Linked Immunosorbent Assay for Antibodies Against the Tumor-Associated Antigen-Derived Cytotoxic T-Lymphocyte Epitope. Methods in Molecular Biology, 217–223. https://doi.org/10.1007/978-1-0716-3914-6_17
Oji, Y., Hashimoto, N., Tsuboi, A., Murakami, Y., Iwai, M., Kagawa, N., Chiba, Y., Izumoto, S., Elisseeva, O., Ichinohasama, R., Sakamoto, J., Morita, S., Nakajima, H., Takashima, S., Nakae, Y., Nakata, J., Kawakami, M., Nishida, S., Hosen, N., & Fujiki, F. (2016). Association of WT1 IgG antibody against WT1 peptide with prolonged survival in glioblastoma multiforme patients vaccinated with WT1 peptide. International Journal of Cancer, 139(6), 1391–1401. https://doi.org/10.1002/ijc.30182
Palomares, F., Pina, A., Hala Dakhaoui, Leiva-Castro, C., Munera-Rodriguez, A. M., Cejudo-Guillen, M., Granados, B., Alba, G., Santa-Maria, C., Sobrino, F., & Lopez-Enriquez, S. (2024). Dendritic Cells as a Therapeutic Strategy in Acute Myeloid Leukemia: Vaccines. Vaccines, 12(2), 165–165. https://doi.org/10.3390/vaccines12020165
Pan, X., Gao, M., Sun, Y., Zhou, Y., Wang, K., Wang, Y., Xu, L., Zhang, X., Huang, X., & Zhao, X. (2022). Significance of WT1 and multiparameter flow cytometry assessment in patients with chronic myelomonocytic leukemia receiving allogeneic hematopoietic stem cell transplantation. International Journal of Laboratory Hematology, 44(3), 510–517. https://doi.org/10.1111/ijlh.13788
Panuzzo, C., Jovanovski, A., Ali, M. S., Cilloni, D., & Pergolizzi, B. (2022). Revealing the Mysteries of Acute Myeloid Leukemia: From Quantitative PCR through Next-Generation Sequencing and Systemic Metabolomic Profiling. Journal of Clinical Medicine, 11(3), 483. https://doi.org/10.3390/jcm11030483
Rafiq, S., Purdon, T. J., Daniyan, A. F., Koneru, M., Dao, T., Liu, C., Scheinberg, D. A., & Brentjens, R. J. (2016). Optimized T-cell receptor-mimic chimeric antigen receptor T cells directed toward the intracellular Wilms Tumor 1 antigen. Leukemia, 31(8), 1788–1797. https://doi.org/10.1038/leu.2016.373
Rampal, R., & Figueroa, M. E. (2016). Wilms tumor 1 mutations in the pathogenesis of acute myeloid leukemia. Haematologica, 101(6), 672–679. https://doi.org/10.3324/haematol.2015.141796
Romanova, E. I., Zubritskiy, Anatoliy V, Lioznova, A. V., Ogunleye, A. J., Golotin, Vasily A, Guts, A. A., Lennartsson, A., Demidov, Oleg N, & Medvedeva, Yulia A. (2022). RUNX1/CEBPA Mutation in Acute Myeloid Leukemia Promotes Hypermethylation and Indicates for Demethylation Therapy. International Journal of Molecular Sciences, 23(19), 11413. https://doi.org/10.3390/ijms231911413
Ruggiero, E., Liu, D., Prodeus, A., Becker, A. M., Foisey, M., Balwani, I., Dutta, I., Zhang, Q., Arredouani, S. M., McKee, M., Ciceri, F., Sepp-Lorenzino, L., Bonini, C., & Schultes, B. C. (2020). NTLA5001, a T Cell Product Candidate with CRISPR-Based Targeted Insertion of a High-Avidity, Natural, WT1-Specific TCR, Shows Efficacy in In Vivo Models of AML and ALL. Blood, 136(Supplement 1), 32–33. https://doi.org/10.1182/blood-2020-143119
Schuurhuis, G. J., Heuser, M., Freeman, S., Béné, M.-C., Buccisano, F., Cloos, J., Grimwade, D., Haferlach, T., Hills, R. K., Hourigan, C. S., Jorgensen, J. L., Kern, W., Lacombe, F., Maurillo, L., Preudhomme, C., van der Reijden, B. A., Thiede, C., Venditti, A., Vyas, P., & Wood, B. L. (2018). Minimal/measurable residual disease in AML: a consensus document from the European LeukemiaNet MRD Working Party. Blood, 131(12), 1275–1291. https://doi.org/10.1182/blood-2017-09-801498
Tawara, I., Kageyama, S., Miyahara, Y., Fujiwara, H., Nishida, T., Yoshiki Akatsuka, Ikeda, H., Tanimoto, K., Seitaro Terakura, Murata, M., Inaguma, Y., Masahiro Masuya, Inoue, N., Tomohide Kidokoro, Okamoto, S., Daisuke Tomura, Hideto Chono, Ikuei Nukaya, Junichi Mineno, & Tomoki Naoe. (2017). Safety and persistence of WT1-specific T-cell receptor gene−transduced lymphocytes in patients with AML and MDS. Blood, 130(18), 1985–1994. https://doi.org/10.1182/blood-2017-06-791202
Tian, Z., Liu, M., Zhang, Y., & Wang, X. (2021). Bispecific T cell engagers: an emerging therapy for management of hematologic malignancies. Journal of Hematology & Oncology, 14(1). https://doi.org/10.1186/s13045-021-01084-4
Vakiti, A., & Mewawalla, P. (2024). Cancer, Acute Myeloid Leukemia (AML, Erythroid Leukemia, Myelodysplasia-Related Leukemia, BCR-ABL Chronic Leukemia). Nih.gov; StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK507875/
van de Loosdrecht, A. A., van Wetering, S., Santegoets, S. J. A. M., Singh, S. K., Eeltink, C. M., den Hartog, Y., Koppes, M., Kaspers, J., Ossenkoppele, G. J., Kruisbeek, A. M., & de Gruijl, T. D. (2018). A novel allogeneic off-the-shelf dendritic cell vaccine for post-remission treatment of elderly patients with acute myeloid leukemia. Cancer Immunology, Immunotherapy: CII, 67(10), 1505–1518. https://doi.org/10.1007/s00262-018-2198-9
Yang, L., Han, Y., Saurez Saiz, F., & Minden, M. D. (2007). A tumor suppressor and oncogene: the WT1 story. Leukemia, 21(5), 868–876. https://doi.org/10.1038/sj.leu.2404624
Zhang, R., Yang, J. Y., Sun, H. Q., Jia, H., Liao, J., Shi, Y. J., & Li, G. (2015). Comparison of minimal residual disease (MRD) monitoring by WT1 quantification between childhood acute myeloid leukemia and acute lymphoblastic leukemia. European Review for Medical and Pharmacological Sciences, 19(14), 2679–2688. https://pubmed.ncbi.nlm.nih.gov/26221900/
Zhou, B., Jin, X., Jin, W., Huang, X., Wu, Y., Li, H., Zhu, W., Qin, X., Ye, H., & Gao, S. (2020). WT1 facilitates the self-renewal of leukemia-initiating cells through the upregulation of BCL2L2: WT1-BCL2L2 axis as a new acute myeloid leukemia therapy target. Journal of Translational Medicine, 18(1). https://doi.org/10.1186/s12967-020-02384-y
Zhou, Y., Huang, G., Cai, X., Liu, Y., Qian, B., & Li, D. (2024). Global, regional, and national burden of acute myeloid leukemia, 1990–2021: a systematic analysis for the global burden of disease study 2021. Biomarker Research, 12(1). https://doi.org/10.1186/s40364-024-00649-y
Published
2026-03-31
How to Cite
Rindiarti, A., & Harsono, Y. (2026). Potential Use of WT1 as a Diagnostic and Therapeutic Marker of Acute Myeloid Leukemia: A Review. Indonesian Journal of Life Sciences, 8(01), 170-187. https://doi.org/https://doi.org/10.54250/ijls.v8i01.270
Issue
Section
Cell and Molecular Biology
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