{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T10:11:32Z","timestamp":1776852692300,"version":"3.51.2"},"reference-count":54,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,6,25]],"date-time":"2021-06-25T00:00:00Z","timestamp":1624579200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,6,25]],"date-time":"2021-06-25T00:00:00Z","timestamp":1624579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Commun Biol"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The presence of FMS-like tyrosine kinase 3-internal tandem duplication (<jats:italic>FLT3<\/jats:italic>-ITD) is one of the most frequent mutations in acute myeloid leukemia (AML) and is associated with an unfavorable prognosis. FLT3 inhibitors, such as midostaurin, are used clinically but fail to entirely eradicate <jats:italic>FLT3<\/jats:italic>-ITD\u2009+\u2009AML. This study introduces a new perspective and highlights the impact of RAC1-dependent actin cytoskeleton remodeling on resistance to midostaurin in AML. RAC1 hyperactivation leads resistance via hyperphosphorylation of the positive regulator of actin polymerization N-WASP and antiapoptotic BCL-2. RAC1\/N-WASP, through ARP2\/3 complex activation, increases the number of actin filaments, cell stiffness and adhesion forces to mesenchymal stromal cells (MSCs) being identified as a biomarker of resistance. Midostaurin resistance can be overcome by a combination of midostaruin, the BCL-2 inhibitor venetoclax and the RAC1 inhibitor Eht1864 in midostaurin-resistant AML cell lines and primary samples, providing the first evidence of a potential new treatment approach to eradicate <jats:italic>FLT3<\/jats:italic>-ITD\u2009+\u2009AML.<\/jats:p>","DOI":"10.1038\/s42003-021-02215-w","type":"journal-article","created":{"date-parts":[[2021,6,25]],"date-time":"2021-06-25T10:03:07Z","timestamp":1624615387000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Actin cytoskeleton deregulation confers midostaurin resistance in FLT3-mutant acute myeloid leukemia"],"prefix":"10.1038","volume":"4","author":[{"given":"Andoni","family":"Garitano-Trojaola","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0560-9187","authenticated-orcid":false,"given":"Ana","family":"Sancho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ralph","family":"G\u00f6tz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Eiring","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanne","family":"Walz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hardikkumar","family":"Jetani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jesus","family":"Gil-Pulido","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5396-6584","authenticated-orcid":false,"given":"Matteo Claudio","family":"Da Via","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva","family":"Teufel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadine","family":"Rhodes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3927-9163","authenticated-orcid":false,"given":"Larissa","family":"Haertle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Estibaliz","family":"Arellano-Viera","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raoul","family":"Tibes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Rosenwald","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leo","family":"Rasche","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2280-2202","authenticated-orcid":false,"given":"Michael","family":"Hudecek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1692-3219","authenticated-orcid":false,"given":"Markus","family":"Sauer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3167-8466","authenticated-orcid":false,"given":"J\u00fcrgen","family":"Groll","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7680-0819","authenticated-orcid":false,"given":"Hermann","family":"Einsele","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabrina","family":"Kraus","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7011-0286","authenticated-orcid":false,"given":"Martin K.","family":"Kort\u00fcm","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,6,25]]},"reference":[{"key":"2215_CR1","doi-asserted-by":"publisher","DOI":"10.1038\/srep11702","volume":"5","author":"YY Ke","year":"2015","unstructured":"Ke, Y. Y. et al. Homology modeling of DFG-in FMS-like tyrosine kinase 3 (FLT3) and structure-based virtual screening for inhibitor identification. Sci. Rep. 5, 11702 (2015).","journal-title":"Sci. Rep."},{"key":"2215_CR2","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1038\/nature11016","volume":"485","author":"CC Smith","year":"2012","unstructured":"Smith, C. C. et al. Validation of ITD mutations in FLT3 as a therapeutic target in human acute myeloid leukaemia. Nature 485, 260\u2013263 (2012).","journal-title":"Nature"},{"key":"2215_CR3","doi-asserted-by":"publisher","first-page":"1241","DOI":"10.1016\/j.chembiol.2010.09.010","volume":"17","author":"LM Wodicka","year":"2010","unstructured":"Wodicka, L. M. et al. Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry. Chem. Biol. 17, 1241\u20131249 (2010).","journal-title":"Chem. Biol."},{"key":"2215_CR4","first-page":"586","volume":"11","author":"M Levis","year":"2013","unstructured":"Levis, M. Quizartinib in acute myeloid leukemia. Clin. Adv. Hematol. Oncol. 11, 586\u2013588 (2013).","journal-title":"Clin. Adv. Hematol. Oncol."},{"key":"2215_CR5","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1111\/j.1365-2141.2007.06700.x","volume":"138","author":"S Knapper","year":"2007","unstructured":"Knapper, S. FLT3 inhibition in acute myeloid leukaemia. Br. J. Haematol. 138, 687\u2013699 (2007).","journal-title":"Br. J. Haematol."},{"key":"2215_CR6","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1016\/S1535-6108(02)00069-7","volume":"1","author":"E Weisberg","year":"2002","unstructured":"Weisberg, E. et al. Inhibition of mutant FLT3 receptors in leukemia cells by the small molecule tyrosine kinase inhibitor PKC412. Cancer Cell 1, 433\u2013443 (2002).","journal-title":"Cancer Cell"},{"key":"2215_CR7","doi-asserted-by":"publisher","first-page":"3669","DOI":"10.1182\/blood-2003-11-3775","volume":"103","author":"BD Smith","year":"2004","unstructured":"Smith, B. D. et al. Single-agent CEP-701, a novel FLT3 inhibitor, shows biologic and clinical activity in patients with relapsed or refractory acute myeloid leukemia. Blood 103, 3669\u20133676 (2004).","journal-title":"Blood"},{"key":"2215_CR8","doi-asserted-by":"publisher","first-page":"3477","DOI":"10.1182\/blood-2006-04-015743","volume":"108","author":"M Levis","year":"2006","unstructured":"Levis, M. et al. Plasma inhibitory activity (PIA): a pharmacodynamic assay reveals insights into the basis for cytotoxic response to FLT3 inhibitors. Blood 108, 3477\u20133483 (2006).","journal-title":"Blood"},{"key":"2215_CR9","doi-asserted-by":"publisher","first-page":"3069","DOI":"10.1182\/blood-2012-01-403493","volume":"120","author":"AB Williams","year":"2012","unstructured":"Williams, A. B. et al. Fluvastatin inhibits FLT3 glycosylation in human and murine cells and prolongs survival of mice with FLT3\/ITD leukemia. Blood 120, 3069\u20133079 (2012).","journal-title":"Blood"},{"key":"2215_CR10","doi-asserted-by":"publisher","first-page":"2418","DOI":"10.3324\/haematol.2018.208843","volume":"104","author":"M Wu","year":"2019","unstructured":"Wu, M., Li, L., Hamaker, M., Small, D. & Duffield, A. S. FLT3-ITD cooperates with Rac1 to modulate the sensitivity of leukemic cells to chemotherapeutic agents via regulation of DNA repair pathways. Haematologica 104, 2418\u20132428. (2019).","journal-title":"Haematologica"},{"key":"2215_CR11","doi-asserted-by":"publisher","first-page":"e27958","DOI":"10.4161\/sgtp.27958","volume":"5","author":"CD Lawson","year":"2014","unstructured":"Lawson, C. D. & Burridge, K. The on-off relationship of Rho and Rac during integrin-mediated adhesion and cell migration. Small GTPases 5, e27958 (2014).","journal-title":"Small GTPases"},{"key":"2215_CR12","doi-asserted-by":"publisher","first-page":"3494","DOI":"10.1021\/bi062152y","volume":"46","author":"N Tomasevic","year":"2007","unstructured":"Tomasevic, N. et al. Differential regulation of WASP and N-WASP by Cdc42, Rac1, Nck, and PI(4,5)P2. Biochemistry 46, 3494\u20133502 (2007).","journal-title":"Biochemistry"},{"key":"2215_CR13","doi-asserted-by":"publisher","first-page":"1801","DOI":"10.1242\/jcs.114.10.1801","volume":"114","author":"T Takenawa","year":"2001","unstructured":"Takenawa, T. & Miki, H. WASP and WAVE family proteins: key molecules for rapid rearrangement of cortical actin filaments and cell movement. J. Cell Sci. 114, 1801\u20131809 (2001).","journal-title":"J. Cell Sci."},{"key":"2215_CR14","doi-asserted-by":"publisher","first-page":"1001","DOI":"10.1083\/jcb.150.5.1001","volume":"150","author":"C Yang","year":"2000","unstructured":"Yang, C. et al. Profilin enhances Cdc42-induced nucleation of actin polymerization. J. Cell Biol. 150, 1001\u20131012 (2000).","journal-title":"J. Cell Biol."},{"key":"2215_CR15","doi-asserted-by":"publisher","first-page":"6425","DOI":"10.1038\/s41388-018-0422-x","volume":"37","author":"A Castagnino","year":"2018","unstructured":"Castagnino, A. et al. Coronin 1C promotes triple-negative breast cancer invasiveness through regulation of MT1-MMP traffic and invadopodia function. Oncogene 37, 6425\u20136441. (2018).","journal-title":"Oncogene"},{"key":"2215_CR16","doi-asserted-by":"publisher","first-page":"1353","DOI":"10.1016\/j.bbrc.2016.12.040","volume":"482","author":"A Salvi","year":"2017","unstructured":"Salvi, A. & Thanabalu, T. WIP promotes in-vitro invasion ability, anchorage independent growth and EMT progression of A549 lung adenocarcinoma cells by regulating RhoA levels. Biochem. Biophys. Res. Commun. 482, 1353\u20131359 (2017).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2215_CR17","doi-asserted-by":"publisher","first-page":"6214","DOI":"10.1182\/blood-2010-08-301283","volume":"117","author":"R Velaithan","year":"2011","unstructured":"Velaithan, R. et al. The small GTPase Rac1 is a novel binding partner of Bcl-2 and stabilizes its antiapoptotic activity. Blood 117, 6214\u20136226 (2011).","journal-title":"Blood"},{"key":"2215_CR18","doi-asserted-by":"publisher","first-page":"17970","DOI":"10.18632\/oncotarget.7602","volume":"7","author":"G Li","year":"2016","unstructured":"Li, G. et al. Rac1b enhances cell survival through activation of the JNK2\/c-JUN\/Cyclin-D1 and AKT2\/MCL1 pathways. Oncotarget 7, 17970\u201317985 (2016).","journal-title":"Oncotarget"},{"key":"2215_CR19","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.critrevonc.2018.01.012","volume":"124","author":"GA Cardama","year":"2018","unstructured":"Cardama, G. A. et al. Relevance of small GTPase Rac1 pathway in drug and radio-resistance mechanisms: Opportunities in cancer therapeutics. Crit. Rev. Oncol. Hematol. 124, 29\u201336 (2018).","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"2215_CR20","doi-asserted-by":"publisher","first-page":"35666","DOI":"10.1074\/jbc.M703571200","volume":"282","author":"A Shutes","year":"2007","unstructured":"Shutes, A. et al. Specificity and mechanism of action of EHT 1864, a novel small molecule inhibitor of Rac family small GTPases. J. Biol. Chem. 282, 35666\u201335678 (2007).","journal-title":"J. Biol. Chem."},{"key":"2215_CR21","doi-asserted-by":"publisher","first-page":"E472","DOI":"10.1073\/pnas.1100236108","volume":"108","author":"SB Padrick","year":"2011","unstructured":"Padrick, S. B., Doolittle, L. K., Brautigam, C. A., King, D. S. & Rosen, M. K. Arp2\/3 complex is bound and activated by two WASP proteins. Proc. Natl Acad. Sci. USA 108, E472\u2013E479 (2011).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"2215_CR22","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-43975-0","volume":"9","author":"T Kunschmann","year":"2019","unstructured":"Kunschmann, T. et al. The Small GTPase Rac1 Increases Cell Surface Stiffness and Enhances 3D Migration Into Extracellular Matrices. Sci. Rep. 9, 7675 (2019).","journal-title":"Sci. Rep."},{"key":"2215_CR23","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1038\/nature08908","volume":"463","author":"DA Fletcher","year":"2010","unstructured":"Fletcher, D. A. & Mullins, R. D. Cell mechanics and the cytoskeleton. Nature 463, 485\u2013492 (2010).","journal-title":"Nature"},{"key":"2215_CR24","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1038\/347095a0","volume":"347","author":"PA Janmey","year":"1990","unstructured":"Janmey, P. A. et al. Effect of ATP on actin filament stiffness. Nature 347, 95\u201399 (1990).","journal-title":"Nature"},{"key":"2215_CR25","doi-asserted-by":"publisher","first-page":"2501","DOI":"10.1021\/nl901384x","volume":"9","author":"A Meister","year":"2009","unstructured":"Meister, A. et al. FluidFM: combining atomic force microscopy and nanofluidics in a universal liquid delivery system for single cell applications and beyond. Nano Lett. 9, 2501\u20132507 (2009).","journal-title":"Nano Lett."},{"key":"2215_CR26","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1182\/blood-2009-01-199281","volume":"114","author":"AK Azab","year":"2009","unstructured":"Azab, A. K. et al. RhoA and Rac1 GTPases play major and differential roles in stromal cell-derived factor-1-induced cell adhesion and chemotaxis in multiple myeloma. Blood 114, 619\u2013629 (2009).","journal-title":"Blood"},{"key":"2215_CR27","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1016\/S1097-2765(01)00320-3","volume":"8","author":"EH Cheng","year":"2001","unstructured":"Cheng, E. H. et al. BCL-2, BCL-X(L) sequester BH3 domain-only molecules preventing BAX- and BAK-mediated mitochondrial apoptosis. Mol. Cell 8, 705\u2013711 (2001).","journal-title":"Mol. Cell"},{"key":"2215_CR28","doi-asserted-by":"publisher","first-page":"2969","DOI":"10.1182\/blood-2002-12-3813","volume":"102","author":"Y Minami","year":"2003","unstructured":"Minami, Y. et al. Different antiapoptotic pathways between wild-type and mutated FLT3: insights into therapeutic targets in leukemia. Blood 102, 2969\u20132975 (2003).","journal-title":"Blood"},{"key":"2215_CR29","first-page":"2140","volume":"9","author":"K Spiekermann","year":"2003","unstructured":"Spiekermann, K., Bagrintseva, K., Schwab, R., Schmieja, K. & Hiddemann, W. Overexpression and constitutive activation of FLT3 induces STAT5 activation in primary acute myeloid leukemia blast cells. Clin. Cancer Res. 9, 2140\u20132150 (2003).","journal-title":"Clin. Cancer Res."},{"key":"2215_CR30","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1186\/1756-8722-2-33","volume":"2","author":"J Zhou","year":"2009","unstructured":"Zhou, J., Goh, B. C., Albert, D. H. & Chen, C. S. ABT-869, a promising multi-targeted tyrosine kinase inhibitor: from bench to bedside. J. Hematol. Oncol. 2, 33 (2009).","journal-title":"J. Hematol. Oncol."},{"key":"2215_CR31","doi-asserted-by":"publisher","first-page":"80","DOI":"10.5306\/wjco.v2.i2.80","volume":"2","author":"F Broekman","year":"2011","unstructured":"Broekman, F., Giovannetti, E. & Peters, G. J. Tyrosine kinase inhibitors: Multi-targeted or single-targeted? World J. Clin. Oncol. 2, 80\u201393 (2011).","journal-title":"World J. Clin. Oncol."},{"key":"2215_CR32","doi-asserted-by":"publisher","first-page":"71","DOI":"10.4161\/21541248.2014.989789","volume":"6","author":"CC Campa","year":"2015","unstructured":"Campa, C. C., Ciraolo, E., Ghigo, A., Germena, G. & Hirsch, E. Crossroads of PI3K and Rac pathways. Small GTPases 6, 71\u201380 (2015).","journal-title":"Small GTPases"},{"key":"2215_CR33","doi-asserted-by":"publisher","first-page":"1333","DOI":"10.1016\/j.celrep.2014.10.039","volume":"9","author":"A Chatterjee","year":"2014","unstructured":"Chatterjee, A. et al. Regulation of Stat5 by FAK and PAK1 in Oncogenic FLT3- and KIT-Driven Leukemogenesis. Cell Rep. 9, 1333\u20131348 (2014).","journal-title":"Cell Rep."},{"key":"2215_CR34","doi-asserted-by":"publisher","first-page":"6815","DOI":"10.1158\/1078-0432.CCR-19-0832","volume":"25","author":"J Ma","year":"2019","unstructured":"Ma, J. et al. Inhibition of Bcl-2 synergistically enhances the antileukemic activity of midostaurin and gilteritinib in preclinical models of FLT3-mutated acute myeloid leukemia. Clin. Cancer Res. 25, 6815\u20136826. (2019).","journal-title":"Clin. Cancer Res."},{"key":"2215_CR35","doi-asserted-by":"publisher","first-page":"2295","DOI":"10.1101\/gad.11.18.2295","volume":"11","author":"L Van Aelst","year":"1997","unstructured":"Van Aelst, L. & D\u2019Souza-Schorey, C. Rho GTPases and signaling networks. Genes Dev. 11, 2295\u20132322 (1997).","journal-title":"Genes Dev."},{"key":"2215_CR36","doi-asserted-by":"publisher","first-page":"1229","DOI":"10.1016\/S1097-2765(03)00172-2","volume":"11","author":"GO Cory","year":"2003","unstructured":"Cory, G. O., Cramer, R., Blanchoin, L. & Ridley, A. J. Phosphorylation of the WASP-VCA domain increases its affinity for the Arp2\/3 complex and enhances actin polymerization by WASP. Mol. Cell 11, 1229\u20131239 (2003).","journal-title":"Mol. Cell"},{"key":"2215_CR37","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1093\/jb\/mvm034","volume":"141","author":"O Nakanishi","year":"2007","unstructured":"Nakanishi, O., Suetsugu, S., Yamazaki, D. & Takenawa, T. Effect of WAVE2 phosphorylation on activation of the Arp2\/3 complex. J. Biochem 141, 319\u2013325 (2007).","journal-title":"J. Biochem"},{"key":"2215_CR38","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1158\/0008-5472.CAN-16-2060","volume":"77","author":"K Kazazian","year":"2017","unstructured":"Kazazian, K. et al. Plk4 promotes cancer invasion and metastasis through Arp2\/3 complex regulation of the actin cytoskeleton. Cancer Res. 77, 434\u2013447. (2017).","journal-title":"Cancer Res."},{"key":"2215_CR39","doi-asserted-by":"publisher","first-page":"2706","DOI":"10.1111\/cas.13711","volume":"109","author":"Y Lu","year":"2018","unstructured":"Lu, Y. et al. Profilin 1 induces drug resistance through Beclin1 complex-mediated autophagy in multiple myeloma. Cancer Sci. 109, 2706\u20132716. (2018).","journal-title":"Cancer Sci."},{"key":"2215_CR40","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1038\/347044a0","volume":"347","author":"KC Holmes","year":"1990","unstructured":"Holmes, K. C., Popp, D., Gebhard, W. & Kabsch, W. Atomic model of the actin filament. Nature 347, 44\u201349 (1990).","journal-title":"Nature"},{"key":"2215_CR41","doi-asserted-by":"publisher","first-page":"5749","DOI":"10.1016\/j.biomaterials.2014.03.058","volume":"35","author":"TV Nguyen","year":"2014","unstructured":"Nguyen, T. V., Sleiman, M., Moriarty, T., Herrick, W. G. & Peyton, S. R. Sorafenib resistance and JNK signaling in carcinoma during extracellular matrix stiffening. Biomaterials 35, 5749\u20135759 (2014).","journal-title":"Biomaterials"},{"key":"2215_CR42","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1002\/bit.25097","volume":"111","author":"S Zustiak","year":"2014","unstructured":"Zustiak, S., Nossal, R. & Sackett, D. L. Multiwell stiffness assay for the study of cell responsiveness to cytotoxic drugs. Biotechnol. Bioeng. 111, 396\u2013403 (2014).","journal-title":"Biotechnol. Bioeng."},{"key":"2215_CR43","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1016\/j.nano.2011.09.015","volume":"8","author":"S Sharma","year":"2012","unstructured":"Sharma, S. et al. Correlative nanomechanical profiling with super-resolution F-actin imaging reveals novel insights into mechanisms of cisplatin resistance in ovarian cancer cells. Nanomedicine 8, 757\u2013766 (2012).","journal-title":"Nanomedicine"},{"key":"2215_CR44","doi-asserted-by":"publisher","first-page":"5631","DOI":"10.1158\/0008-5472.CAN-18-0441","volume":"78","author":"A Al Absi","year":"2018","unstructured":"Al Absi, A. et al. Actin cytoskeleton remodeling drives breast cancer cell escape from natural killer-mediated cytotoxicity. Cancer Res. 78, 5631\u20135643. (2018).","journal-title":"Cancer Res."},{"key":"2215_CR45","doi-asserted-by":"publisher","first-page":"75","DOI":"10.4161\/bioa.20975","volume":"2","author":"M Desouza","year":"2012","unstructured":"Desouza, M., Gunning, P. W. & Stehn, J. R. The actin cytoskeleton as a sensor and mediator of apoptosis. Bioarchitecture 2, 75\u201387 (2012).","journal-title":"Bioarchitecture"},{"key":"2215_CR46","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1038\/s41375-018-0261-3","volume":"33","author":"DM Moujalled","year":"2019","unstructured":"Moujalled, D. M. et al. Combining BH3-mimetics to target both BCL-2 and MCL1 has potent activity in pre-clinical models of acute myeloid leukemia. Leukemia 33, 905\u2013917. (2019).","journal-title":"Leukemia"},{"key":"2215_CR47","doi-asserted-by":"publisher","first-page":"2098","DOI":"10.1038\/s41375-019-0421-0","volume":"33","author":"KT Siu","year":"2019","unstructured":"Siu, K. T. et al. BCL2 blockade overcomes MCL1 resistance in multiple myeloma. Leukemia 33, 2098\u20132102. (2019).","journal-title":"Leukemia"},{"key":"2215_CR48","doi-asserted-by":"crossref","unstructured":"Schubert, E. K. A., Emrich, T., Z\u00fcfle, A., Schmid, K. A. & Zimek, A. A framework for clustering uncertain data. 8 (Proceedings of the VLDB Endowment, 2015) https:\/\/dl.acm.org\/doi\/10.14778\/2824032.2824115.","DOI":"10.14778\/2824032.2824115"},{"key":"2215_CR49","doi-asserted-by":"publisher","first-page":"1040","DOI":"10.1038\/nmeth.2224","volume":"9","author":"S Wolter","year":"2012","unstructured":"Wolter, S. et al. rapidSTORM: accurate, fast open-source software for localization microscopy. Nat. Methods 9, 1040\u20131041 (2012).","journal-title":"Nat. Methods"},{"key":"2215_CR50","doi-asserted-by":"publisher","first-page":"12842","DOI":"10.18632\/oncotarget.24401","volume":"9","author":"A Garitano-Trojaola","year":"2018","unstructured":"Garitano-Trojaola, A. et al. Deregulation of linc-PINT in acute lymphoblastic leukemia is implicated in abnormal proliferation of leukemic cells. Oncotarget 9, 12842\u201312852. (2018).","journal-title":"Oncotarget"},{"key":"2215_CR51","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.ccell.2016.05.011","volume":"30","author":"V Stavropoulou","year":"2016","unstructured":"Stavropoulou, V. et al. MLL-AF9 expression in hematopoietic stem cells drives a highly invasive AML expressing EMT-related genes linked to poor outcome. Cancer Cell 30, 43\u201358 (2016).","journal-title":"Cancer Cell"},{"key":"2215_CR52","doi-asserted-by":"crossref","unstructured":"Belinky, F. et al. PathCards: multi-source consolidation of human biological pathways. Database (Oxford). 2015, bav006 (2015).","DOI":"10.1093\/database\/bav006"},{"key":"2215_CR53","doi-asserted-by":"publisher","first-page":"46152","DOI":"10.1038\/srep46152","volume":"7","author":"A Sancho","year":"2017","unstructured":"Sancho, A., Vandersmissen, I., Craps, S., Luttun, A., & Groll, J. A new strategy to measure intercellular adhesion forces in mature cell-cell contacts. Sci. Rep. 7, 46152 (2017).","journal-title":"Sci. Rep."},{"key":"2215_CR54","doi-asserted-by":"publisher","first-page":"12406","DOI":"10.1021\/jacs.7b07272","volume":"139","author":"MS Michie","year":"2017","unstructured":"Michie, M. S. et al. Cyanine conformational restraint in the far-red range. J. Am. Chem. Soc. 139, 12406\u201312409 (2017).","journal-title":"J. Am. Chem. Soc."}],"container-title":["Communications Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s42003-021-02215-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-021-02215-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-021-02215-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T19:32:05Z","timestamp":1670095925000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s42003-021-02215-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,25]]},"references-count":54,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["2215"],"URL":"https:\/\/doi.org\/10.1038\/s42003-021-02215-w","relation":{},"ISSN":["2399-3642"],"issn-type":[{"value":"2399-3642","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,25]]},"assertion":[{"value":"20 October 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 May 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 June 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"799"}}