Masiakowski P, Carroll RD. A novel family of cell surface receptors with tyrosine kinase-like domain. J Biol Chem. 1992;267:26181–90.
Google Scholar
Oishi I, Takeuchi S, Hashimoto R, Nagabukuro A, Ueda T, Liu ZJ, et al. Spatio-temporally regulated expression of receptor tyrosine kinases, mRor1, mRor2, during mouse development: implications in development and function of the nervous system. Genes Cells. 1999;4:41–56.
Google Scholar
Al-Shawi R, Ashton SV, Underwood C, Simons JP. Expression of the Ror1 and Ror2 receptor tyrosine kinase genes during mouse development. Dev Genes Evol. 2001;211:161–71.
Google Scholar
Yoda A, Oishi I, Minami Y. Expression and function of the Ror-family receptor tyrosine kinases during development: lessons from genetic analyses of nematodes, mice, and humans. J Recept Signal Transduct Res. 2003;23:1–15.
Google Scholar
Fukuda T, Chen L, Endo T, Tang L, Lu D, Castro JE, et al. Antisera induced by infusions of autologous Ad-CD154-leukemia B cells identify ROR1 as an oncofetal antigen and receptor for Wnt5a. Proc Natl Acad Sci USA. 2008;105:3047–52.
Google Scholar
Hudecek M, Schmitt TM, Baskar S, Lupo-Stanghellini MT, Nishida T, Yamamoto TN, et al. The B-cell tumor-associated antigen ROR1 can be targeted with T cells modified to express a ROR1-specific chimeric antigen receptor. Blood. 2010;116:4532–41.
Google Scholar
Zhang S, Chen L, Wang-Rodriguez J, Zhang L, Cui B, Frankel W, et al. The onco-embryonic antigen ROR1 is expressed by a variety of human cancers. Am J Pathol. 2012;181:1903–10.
Google Scholar
Malta TM, Sokolov A, Gentles AJ, Burzykowski T, Poisson L, Weinstein JN, et al. Machine learning identifies stemness features associated with oncogenic dedifferentiation. Cell. 2018;173:338–54.e315.
Google Scholar
Hanahan D. Hallmarks of cancer: new dimensions. Cancer Discov. 2022;12:31–46.
Google Scholar
Cui B, Ghia EM, Chen L, Rassenti LZ, DeBoever C, Widhopf GF 2nd, et al. High-level ROR1 associates with accelerated disease progression in chronic lymphocytic leukemia. Blood. 2016;128:2931–40.
Google Scholar
Ghia EM, Rassenti LZ, Choi MY, Quijada-Alamo M, Chu E, Widhopf GF 2nd, et al. High expression level of ROR1 and ROR1-signaling associates with venetoclax resistance in chronic lymphocytic leukemia. Leukemia. 2022;36:1609–18.
Google Scholar
Kipps TJ. ROR1: an orphan becomes apparent. Blood. 2022;140:1583–91.
Google Scholar
Widhopf GF 2nd, Cui B, Ghia EM, Chen L, Messer K, Shen Z, et al. ROR1 can interact with TCL1 and enhance leukemogenesis in Emu-TCL1 transgenic mice. Proc Natl Acad Sci USA. 2014;111:793–8.
Google Scholar
Choi MY, Widhopf GF 2nd, Ghia EM, Kidwell RL, Hasan MK, Yu J, et al. Phase I trial: cirmtuzumab inhibits ROR1 signaling and stemness signatures in patients with chronic lymphocytic leukemia. Cell Stem Cell. 2018;22:951–959.e953.
Google Scholar
Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Dohner H, et al. iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL. Blood. 2018;131:2745–60.
Google Scholar
Romano MF, Lamberti A, Tassone P, Alfinito F, Costantini S, Chiurazzi F, et al. Triggering of CD40 antigen inhibits fludarabine-induced apoptosis in B chronic lymphocytic leukemia cells. Blood. 1998;92:990–5.
Google Scholar
Sanchez-Lopez E, Ghia EM, Antonucci L, Sharma N, Rassenti LZ, Xu J, et al. NF-κB-p62-NRF2 survival signaling is associated with high ROR1 expression in chronic lymphocytic leukemia. Cell Death Differ. 2020;27:2206–16.
Google Scholar
Rojo de la Vega M, Chapman E, Zhang DD. NRF2 and the hallmarks of cancer. Cancer Cell. 2018;34:21–43.
Google Scholar
Hallis SP, Kim JM, Kwak MK. Emerging role of NRF2 signaling in cancer stem cell phenotype. Mol Cells. 2023;46:153–64.
Google Scholar
Cordani M, Butera G, Pacchiana R, Masetto F, Mullappilly N, Riganti C, et al. Mutant p53-associated molecular mechanisms of ROS regulation in cancer cells. Biomolecules. 2020;10:361.
Lisek K, Campaner E, Ciani Y, Walerych D, Del Sal G. Mutant p53 tunes the NRF2-dependent antioxidant response to support survival of cancer cells. Oncotarget. 2018;9:20508–23.
Google Scholar
Cirone M, D’Orazi G. NRF2 in Cancer: Cross-Talk with Oncogenic Pathways and Involvement in Gammaherpesvirus-Driven Carcinogenesis. Int J Mol Sci. 2022;24:595.
Wu S, Lu H, Bai Y. Nrf2 in cancers: a double-edged sword. Cancer Med. 2019;8:2252–67.
Google Scholar
O’Brien S, Jones JA, Coutre SE, Mato AR, Hillmen P, Tam C, et al. Ibrutinib for patients with relapsed or refractory chronic lymphocytic leukaemia with 17p deletion (RESONATE-17): a phase 2, open-label, multicentre study. Lancet Oncol. 2016;17:1409–18.
Google Scholar
Sivina M, Kim E, Wierda WG, Ferrajoli A, Jain N, Thompson P, et al. Ibrutinib induces durable remissions in treatment-naive patients with CLL and 17p deletion and/or TP53 mutations. Blood. 2021;138:2589–92.
Google Scholar
Mato AR, Woyach JA, Brown JR, Ghia P, Patel K, Eyre TA, et al. Pirtobrutinib after a covalent BTK inhibitor in chronic lymphocytic leukemia. N Engl J Med. 2023;389:33–44.
Google Scholar
Yu J, Chen L, Cui B, Wu C, Choi MY, Chen Y, et al. Cirmtuzumab inhibits Wnt5a-induced Rac1 activation in chronic lymphocytic leukemia treated with ibrutinib. Leukemia. 2017;31:1333–9.
Google Scholar
National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. 2010 [cited 2017; Available from: Common Terminology Criteria for Adverse Events (CTCAE)
Byrd JC, Furman RR, Coutre SE, Flinn IW, Burger JA, Blum KA, et al. Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. N Engl J Med. 2013;369:32–42.
Google Scholar
Byrd JC, Brown JR, O’Brien S, Barrientos JC, Kay NE, Reddy NM, et al. Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. N Engl J Med. 2014;371:213–23.
Google Scholar
Farooqui MZ, Valdez J, Martyr S, Aue G, Saba N, Niemann CU, et al. Ibrutinib for previously untreated and relapsed or refractory chronic lymphocytic leukaemia with TP53 aberrations: a phase 2, single-arm trial. Lancet Oncol. 2015;16:169–76.
Google Scholar
Burger JA, Tedeschi A, Barr PM, Robak T, Owen C, Ghia P, et al. Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia. N Engl J Med. 2015;373:2425–37.
Google Scholar
Hasan MK, Ghia EM, Rassenti LZ, Widhopf GF 2nd, Kipps TJ. Wnt5a enhances proliferation of chronic lymphocytic leukemia and ERK1/2 phosphorylation via a ROR1/DOCK2-dependent mechanism. Leukemia. 2021;35:1621–30.
Google Scholar
Chen Y, Chen L, Yu J, Ghia EM, Choi MY, Zhang L, et al. Cirmtuzumab blocks Wnt5a/ROR1 stimulation of NF-kappaB to repress autocrine STAT3 activation in chronic lymphocytic leukemia. Blood. 2019;134:1084–94.
Google Scholar
Castro-Mondragon JA, Riudavets-Puig R, Rauluseviciute I, Lemma RB, Turchi L, Blanc-Mathieu R, et al. JASPAR 2022: the 9th release of the open-access database of transcription factor binding profiles. Nucleic Acids Res. 2022;50:D165–D173.
Google Scholar
Malhotra D, Portales-Casamar E, Singh A, Srivastava S, Arenillas D, Happel C, et al. Global mapping of binding sites for Nrf2 identifies novel targets in cell survival response through ChIP-Seq profiling and network analysis. Nucleic Acids Res. 2010;38:5718–34.
Google Scholar
Mo Z, Zhang S, Zhang S. A novel signature based on mTORC1 pathway in hepatocellular carcinoma. J Oncol. 2020;2020:8291036.
Google Scholar
Milacic M, Beavers D, Conley P, Gong C, Gillespie M, Griss J, et al. The reactome pathway knowledgebase 2024. Nucleic Acids Res. 2024;52:D672–D678.
Google Scholar
Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci USA. 2005;102:15545–50.
Google Scholar
Herishanu Y, Perez-Galan P, Liu D, Biancotto A, Pittaluga S, Vire B, et al. The lymph node microenvironment promotes B-cell receptor signaling, NF-kappaB activation, and tumor proliferation in chronic lymphocytic leukemia. Blood. 2011;117:563–74.
Google Scholar
Asher G, Lotem J, Tsvetkov P, Reiss V, Sachs L, Shaul Y. P53 hot-spot mutants are resistant to ubiquitin-independent degradation by increased binding to NAD(P)H:quinone oxidoreductase 1. Proc Natl Acad Sci USA. 2003;100:15065–70.
Google Scholar
Bomben R, Rossi FM, Vit F, Bittolo T, Zucchetto A, Papotti R, et al. Clinical impact of TP53 disruption in chronic lymphocytic leukemia patients treated with ibrutinib: a campus CLL study. Leukemia. 2023;37:914–8.
Google Scholar
Byrd JC, Hillmen P, O’Brien S, Barrientos JC, Reddy NM, Coutre S, et al. Long-term follow-up of the RESONATE phase 3 trial of ibrutinib vs ofatumumab. Blood. 2019;133:2031–42.
Google Scholar
Mato AR, Tang B, Azmi S, Yang K, Zhang X, Stern JC, et al. A clinical practice comparison of patients with chronic lymphocytic leukemia with and without deletion 17p receiving first-line treatment with ibrutinib. Haematologica. 2022;107:2630–40.
Google Scholar
Byrd JC, Woyach JA, Furman RR, Martin P, O’Brien S, Brown JR, et al. Acalabrutinib in treatment-naive chronic lymphocytic leukemia. Blood. 2021;137:3327–38.
Google Scholar
Tam CS, Robak T, Ghia P, Kahl BS, Walker P, Janowski W, et al. Zanubrutinib monotherapy for patients with treatment naive chronic lymphocytic leukemia and 17p deletion. Haematologica. 2021;106:2354–63.
Google Scholar
Ahn IE, Tian X, Wiestner A. Ibrutinib for chronic lymphocytic leukemia with TP53 alterations. N Engl J Med. 2020;383:498–500.
Google Scholar
Allan JN, Shanafelt T, Wiestner A, Moreno C, O’Brien SM, Li J, et al. Long-term efficacy of first-line ibrutinib treatment for chronic lymphocytic leukaemia in patients with TP53 aberrations: a pooled analysis from four clinical trials. Br J Haematol. 2022;196:947–53.
Google Scholar
Ekberg J, Holm C, Jalili S, Richter J, Anagnostaki L, Landberg G, et al. Expression of cyclin A1 and cell cycle proteins in hematopoietic cells and acute myeloid leukemia and links to patient outcome. Eur J Haematol. 2005;75:106–15.
Google Scholar
Huang KC, Yang J, Ng MC, Ng SK, Welch WR, Muto MG, et al. Cyclin A1 expression and paclitaxel resistance in human ovarian cancer cells. Eur J Cancer. 2016;67:152–63.
Google Scholar
Ji P, Agrawal S, Diederichs S, Bäumer N, Becker A, Cauvet T, et al. Cyclin A1, the alternative A-type cyclin, contributes to G1/S cell cycle progression in somatic cells. Oncogene. 2005;24:2739–44.
Google Scholar
Kalaszczynska I, Geng Y, Iino T, Mizuno S, Choi Y, Kondratiuk I, et al. Cyclin A is redundant in fibroblasts but essential in hematopoietic and embryonic stem cells. Cell. 2009;138:352–65.
Google Scholar
Müller-Tidow C, Diederichs S, Schrader MG, Vogt U, Miller K, Berdel WE, et al. Cyclin A1 is highly expressed in aggressive testicular germ cell tumors. Cancer Lett. 2003;190:89–95.
Google Scholar
Ochsenreither S, Majeti R, Schmitt T, Stirewalt D, Keilholz U, Loeb KR, et al. Cyclin-A1 represents a new immunogenic targetable antigen expressed in acute myeloid leukemia stem cells with characteristics of a cancer-testis antigen. Blood. 2012;119:5492–501.
Google Scholar

