[1]

Hong J, Sui P, Li Y, Xu KY, Lee JH, et al. 2025. PSPC1 exerts an oncogenic role in AML by regulating a leukemic transcription program in cooperation with PU.1. Cell Stem Cell 32:463−478.e6

doi: 10.1016/j.stem.2025.01.010
[2]

Li S, Mason CE, Melnick A. 2016. Genetic and epigenetic heterogeneity in acute myeloid leukemia. Current Opinion in Genetics & Development 36:100−106

doi: 10.1016/j.gde.2016.03.011
[3]

Li S, Garrett-Bakelman FE, Chung SS, Sanders MA, Hricik T, et al. 2016. Distinct evolution and dynamics of epigenetic and genetic heterogeneity in acute myeloid leukemia. Nature Medicine 22:792−799

doi: 10.1038/nm.4125
[4]

Zeng AGX, Bansal S, Jin L, Mitchell A, Chen WC, et al. 2022. A cellular hierarchy framework for understanding heterogeneity and predicting drug response in acute myeloid leukemia. Nature Medicine 28:1212−1223

doi: 10.1038/s41591-022-01819-x
[5]

Kantarjian H, Kadia T, DiNardo C, Daver N, Borthakur G, et al. 2021. Acute myeloid leukemia: current progress and future directions. Blood Cancer Journal 11:41

doi: 10.1038/s41408-021-00425-3
[6]

Masetti R, Baccelli F, Leardini D, Locatelli F. 2024. Venetoclax: a new player in the treatment of children with high-risk myeloid malignancies? Blood Advances 8:3583−3595

doi: 10.1182/bloodadvances.2023012041
[7]

Zhu Y, Murtadha M, Liu M, Caserta E, Napolitano O, et al. 2025. Identification of CD84 as a potent survival factor in acute myeloid leukemia. Journal of Clinical Investigation 135:e176818

doi: 10.1172/jci176818
[8]

Lim WA, Pawson T. 2010. Phosphotyrosine signaling: evolving a new cellular communication system. Cell 142:661−667

doi: 10.1016/j.cell.2010.08.023
[9]

Hunter T. 2009. Tyrosine phosphorylation: thirty years and counting. Current Opinion in Cell Biology 21:140−146

doi: 10.1016/j.ceb.2009.01.028
[10]

Robinson DR, Wu YM, Lin SF. 2000. The protein tyrosine kinase family of the human genome. Oncogene 19:5548−5557

doi: 10.1038/sj.onc.1203957
[11]

Tonks NK, Neel BG. 1996. From form to function: signaling by protein tyrosine phosphatases. Cell 87:365−368

doi: 10.1016/s0092-8674(00)81357-4
[12]

Bouyain S. 2015. Protein tyrosine phosphatases. Seminars in Cell & Developmental Biology 37:56−57

doi: 10.1016/j.semcdb.2015.01.004
[13]

Stoker AW. 2005. Protein tyrosine phosphatases and signalling. Journal of Endocrinology 185:19−33

doi: 10.1677/joe.1.06069
[14]

Hendriks WJAJ, Elson A, Harroch S, Pulido R, Stoker A, et al. 2013. Protein tyrosine phosphatases in health and disease. The FEBS Journal 280:708−730

doi: 10.1111/febs.12000
[15]

Manguso RT, Pope HW, Zimmer MD, Brown FD, Yates KB, et al. 2017. In vivo CRISPR screening identifies Ptpn2 as a cancer immunotherapy target. Nature 547:413−418

doi: 10.1038/nature23270
[16]

Song J, Lan J, Tang J, Luo N. 2022. PTPN2 in the immunity and tumor immunotherapy: a concise review. International Journal of Molecular Sciences 23:10025

doi: 10.3390/ijms231710025
[17]

LaFleur MW, Nguyen TH, Coxe MA, Miller BC, Yates KB, et al. 2019. PTPN2 regulates the generation of exhausted CD8+ T cell subpopulations and restrains tumor immunity. Nature Immunology 20:1335−1347

doi: 10.1038/s41590-019-0480-4
[18]

Wiede F, Lu KH, Du X, Liang S, Hochheiser K, et al. 2020. PTPN2 phosphatase deletion in T cells promotes anti-tumour immunity and CAR T-cell efficacy in solid tumours. The EMBO Journal 39:e103637

doi: 10.15252/embj.2019103637
[19]

Tiganis T, Bennett AM. 2007. Protein tyrosine phosphatase function: the substrate perspective. Biochemical Journal 402:1−15

doi: 10.1042/bj20061548
[20]

Shields BJ, Hauser C, Bukczynska PE, Court NW, Tiganis T. 2008. DNA replication stalling attenuates tyrosine kinase signaling to suppress S phase progression. Cancer Cell 14:166−179

doi: 10.1016/j.ccr.2008.06.003
[21]

Yamamoto T, Sekine Y, Kashima K, Kubota A, Sato N, et al. 2002. The nuclear isoform of protein-tyrosine phosphatase TC-PTP regulates interleukin-6-mediated signaling pathway through STAT3 dephosphorylation. Biochemical and Biophysical Research Communications 297:811−817

doi: 10.1016/s0006-291x(02)02291-x
[22]

Myers MP, Andersen JN, Cheng A, Tremblay ML, Horvath CM, et al. 2001. TYK2 and JAK2 are substrates of protein-tyrosine phosphatase 1B. Journal of Biological Chemistry 276:47771−47774

doi: 10.1074/jbc.c100583200
[23]

Simoncic PD, Lee-Loy A, Barber DL, Tremblay ML, McGlade CJ. 2002. The T cell protein tyrosine phosphatase is a negative regulator of Janus family kinases 1 and 3. Current Biology 12:446−453

doi: 10.1016/s0960-9822(02)00697-8
[24]

Simoncic PD, Bourdeau A, Lee-Loy A, Rohrschneider LR, Tremblay ML, et al. 2006. T-cell protein tyrosine phosphatase (Tcptp) is a negative regulator of colony-stimulating factor 1 signaling and macrophage differentiation. Molecular and Cellular Biology 26:4149−4160

doi: 10.1128/mcb.01932-05
[25]

Zabolotny JM, Bence-Hanulec KK, Stricker-Krongrad A, Haj F, Wang Y, et al. 2002. PTP1B regulates leptin signal transduction in vivo. Developmental Cell 2:489−495

doi: 10.1016/s1534-5807(02)00148-x
[26]

Zabolotny JM, Kim YB, Welsh LA, Kershaw EE, Neel BG, et al. 2008. Protein-tyrosine phosphatase 1B expression is induced by inflammation in vivo. Journal of Biological Chemistry 283:14230−14241

doi: 10.1074/jbc.m800061200
[27]

Lorenzen JA, Dadabay CY, Fischer EH. 1995. COOH-terminal sequence motifs target the T cell protein tyrosine phosphatase to the ER and nucleus. The Journal of Cell Biology 131:631−643

doi: 10.1083/jcb.131.3.631
[28]

Lam MHC, Michell BJ, Fodero-Tavoletti MT, Kemp BE, Tonks NK, et al. 2001. Cellular stress regulates the nucleocytoplasmic distribution of the protein-tyrosine phosphatase TCPTP. Journal of Biological Chemistry 276:37700−37707

doi: 10.1074/jbc.m105128200
[29]

Morales LD, Archbold AK, Olivarez S, Slaga TJ, DiGiovanni J, et al. 2019. The role of T-cell protein tyrosine phosphatase in epithelial carcinogenesis. Molecular Carcinogenesis 58:1640−1647

doi: 10.1002/mc.23078
[30]

van Vliet C, Bukczynska PE, Puryer MA, Sadek CM, Shields BJ, et al. 2005. Selective regulation of tumor necrosis factor–induced Erk signaling by Src family kinases and the T cell protein tyrosine phosphatase. Nature Immunology 6:253−260

doi: 10.1038/ni1169
[31]

Wiede F, Shields BJ, Chew SH, Kyparissoudis K, van Vliet C, et al. 2011. T cell protein tyrosine phosphatase attenuates T cell signaling to maintain tolerance in mice. Journal of Clinical Investigation 121:4758−4774

doi: 10.1172/jci59492
[32]

ten Hoeve J, de Jesus Ibarra-Sanchez M, Fu Y, Zhu W, Tremblay M, et al. 2002. Identification of a nuclear Stat1 protein tyrosine phosphatase. Molecular and Cellular Biology 22:5662−5668

doi: 10.1128/mcb.22.16.5662-5668.2002
[33]

Wiede F, Dudakov JA, Lu KH, Dodd GT, Butt T, et al. 2017. PTPN2 regulates T cell lineage commitment and αβ versus γδ specification. Journal of Experimental Medicine 214:2733−2758

doi: 10.1084/jem.20161903
[34]

Wiede F, Sacirbegovic F, Leong YA, Yu D, Tiganis T. 2017. PTPN2-deficiency exacerbates T follicular helper cell and B cell responses and promotes the development of autoimmunity. Journal of Autoimmunity 76:85−100

doi: 10.1016/j.jaut.2016.09.004
[35]

Grohmann M, Wiede F, Dodd GT, Gurzov EN, Ooi GJ, et al. 2018. Obesity drives STAT-1-dependent NASH and STAT-3-dependent HCC. Cell 175:1289−1306.e20

doi: 10.1016/j.cell.2018.09.053
[36]

Lee H, Kim M, Baek M, Morales LD, Jang IS, et al. 2017. Targeted disruption of TC-PTP in the proliferative compartment augments STAT3 and AKT signaling and skin tumor development. Scientific Reports 7:45077

doi: 10.1038/srep45077
[37]

Shields BJ, Wiede F, Gurzov EN, Wee K, Hauser C, et al. 2013. TCPTP regulates SFK and STAT3 signaling and is lost in triple-negative breast cancers. Molecular and Cellular Biology 33:557−570

doi: 10.1128/mcb.01016-12
[38]

Kleppe M, Lahortiga I, El Chaar T, De Keersmaecker K, Mentens N, et al. 2010. Deletion of the protein tyrosine phosphatase gene PTPN2 in T-cell acute lymphoblastic leukemia. Nature Genetics 42:530−535

doi: 10.1038/ng.587
[39]

Goh PK, Wiede F, Zeissig MN, Britt KL, Liang S, et al. 2022. PTPN2 elicits cell autonomous and non–cell autonomous effects on antitumor immunity in triple-negative breast cancer. Science Advances 8:eabk3338

doi: 10.1126/sciadv.abk3338
[40]

Garrido-Castro AC, Lin NU, Polyak K. 2019. Insights into molecular classifications of triple-negative breast cancer: improving patient selection for treatment. Cancer Discovery 9:176−198

doi: 10.1158/2159-8290.cd-18-1177
[41]

Wang D, Wang W, Song M, Xie Y, Kuang W, et al. 2024. Regulation of protein phosphorylation by PTPN2 and its small-molecule inhibitors/degraders as a potential disease treatment strategy. European Journal of Medicinal Chemistry 277:116774

doi: 10.1016/j.ejmech.2024.116774
[42]

Wang D, Song M, Tong C, Wang W, Li Q, et al. 2025. Development of novel PTPN2/1 inhibitors for the treatment of melanoma. Journal of Medicinal Chemistry 68:21917−21938

doi: 10.1021/acs.jmedchem.5c02300
[43]

Kuang W, Li Q, Wang W, Wang D, Tong C, et al. 2025. Targeting protein tyrosine phosphatase nonreceptor type 2 with a novel inhibitor for the treatment of melanoma. Journal of Medicinal Chemistry 68:24649−24671

doi: 10.1021/acs.jmedchem.5c02622
[44]

Kuang W, Wang X, Ding J, Li J, Ji M, et al. 2022. PTPN2, a key predictor of prognosis for pancreatic adenocarcinoma, significantly regulates cell cycles, apoptosis, and metastasis. Frontiers in Immunology 13:805311

doi: 10.3389/fimmu.2022.805311
[45]

Kress TR, Sabò A, Amati B. 2015. MYC: connecting selective transcriptional control to global RNA production. Nature Reviews Cancer 15:593−607

doi: 10.1038/nrc3984
[46]

Dhanasekaran R, Deutzmann A, Mahauad-Fernandez WD, Hansen AS, Gouw AM, et al. 2022. The MYC oncogene — the grand orchestrator of cancer growth and immune evasion. Nature Reviews Clinical Oncology 19:23−36

doi: 10.1038/s41571-021-00549-2
[47]

Fatma H, Maurya SK, Siddique HR. 2022. Epigenetic modifications of c-MYC: role in cancer cell reprogramming, progression and chemoresistance. Seminars in Cancer Biology 83:166−176

doi: 10.1016/j.semcancer.2020.11.008
[48]

Greenberg PL, Gordeuk V, Issaragrisil S, Siritanaratkul N, Fucharoen S, et al. 2001. Major hematologic diseases in the developing world—new aspects of diagnosis and management of thalassemia, malarial anemia, and acute leukemia. Hematology American Society of Hematology Education Program 2001:479–498

doi: 10.1182/asheducation-2001.1.479
[49]

Wei AH, Loo S, Daver N. 2025. How I treat patients with AML using azacitidine and venetoclax. Blood 145:1237−1250

doi: 10.1182/blood.2024024009
[50]

Goulart H, Wei AH, Kadia TM. 2025. Maintenance therapy in AML: what is the future potential? American Journal of Hematology 100:38−49

doi: 10.1002/ajh.27583
[51]

Grimwade D, Hills RK, Moorman AV, Walker H, Chatters S, et al. 2010. Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials. Blood 116:354−365

doi: 10.1182/blood-2009-11-254441
[52]

Daver N, Schlenk RF, Russell NH, Levis MJ. 2019. Targeting FLT3 mutations in AML: review of current knowledge and evidence. Leukemia 33:299−312

doi: 10.1038/s41375-018-0357-9
[53]

Zhang S, Liu M, Yao Y, Yu B, Liu H. 2021. Targeting LSD1 for acute myeloid leukemia (AML) treatment. Pharmacological Research 164:105335

doi: 10.1016/j.phrs.2020.105335
[54]

Döhner H, Wei AH, Löwenberg B. 2021. Towards precision medicine for AML. Nature Reviews Clinical Oncology 18:577−590

doi: 10.1038/s41571-021-00509-w
[55]

Xie Y, Zhao R, Zheng Y, Li Y, Wu F, et al. 2025. Targeting KPNB1 suppresses AML cells by inhibiting HMGB2 nuclear import. Oncogene 44:1646−1661

doi: 10.1038/s41388-025-03340-0
[56]

Stanford SM, Bottini N. 2017. Targeting tyrosine phosphatases: time to end the stigma. Trends in Pharmacological Sciences 38:524−540

doi: 10.1016/j.tips.2017.03.004
[57]

Krishnan N, Felice C, Rivera K, Pappin DJ, Tonks NK. 2018. DPM-1001 decreased copper levels and ameliorated deficits in a mouse model of Wilson's disease. Genes & Development 32:944−952

doi: 10.1101/gad.314658.118
[58]

Baumgartner CK, Ebrahimi-Nik H, Iracheta-Vellve A, Hamel KM, Olander KE, et al. 2023. The PTPN2/PTPN1 inhibitor ABBV-CLS-484 unleashes potent anti-tumour immunity. Nature 622:850−862

doi: 10.1038/s41586-023-06575-7
[59]

Wang WT, Duan ZW, Xing TY, Hua W, Du KX, et al. 2025. PTPN2 inhibition disrupts mitochondrial renewal and blocks TFRC-mediated mitophagy to exert anti-tumor activities in ALK-positive anaplastic large cell lymphoma. Advanced Science 12:e14282

doi: 10.1002/advs.202414282
[60]

Crown J, O'Shaughnessy J, Gullo G. 2012. Emerging targeted therapies in triple-negative breast cancer. Annals of Oncology 23:vi56−vi65

doi: 10.1093/annonc/mds196