Skip to main content

Advertisement

SpringerLink
Log in

Fast H3K9 methylation promoted by CXCL12 contributes to nuclear changes and invasiveness of T-acute lymphoblastic leukemia cells

  • Article
  • Published:
Oncogene Submit manuscript

Abstract

T-acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy that comprises the accumulation of malignant T-cells. Despite current therapies, failure to conventional treatments and relapse are frequent in children with T-ALL. It is known that the chemokine CXCL12 modulates leukemia survival and dissemination; however, our understanding of molecular mechanisms used by T-ALL cells to infiltrate and respond to leukemia cells-microenvironment interactions is still vague. In the present study, we showed that CXCL12 promoted H3K9 methylation in cell lines and primary T-ALL cells within minutes. We thus identified that CXCL12-mediated H3K9 methylation affected the global chromatin configuration and the nuclear mechanics of T-ALL cells. Importantly, we characterized changes in the genomic profile of T-ALL cells associated with rapid CXCL12 stimulation. We showed that blocking CXCR4 and protein kinase C (PKC) impaired the H3K9 methylation induced by CXCL12 in T-ALL cells. Finally, blocking H3K9 methyltransferases reduced the efficiency of T-ALL cells to deform their nuclei, migrate across confined spaces, and home to spleen and bone marrow in vivo models. Together, our data show novel functions for CXL12 as a master regulator of nuclear deformability and epigenetic changes in T-ALL cells, and its potential as a promising pharmacological target against T-ALL dissemination.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1: CXCL12 promotes H3K9 methylation in T-ALL cells.
Fig. 2: CXCL12 alters the epigenetic and transcriptional landscape of T-ALL cells.
Fig. 3: CXCL12 induces global chromatin compaction in T-ALL cells.
Fig. 4: Fast CXCL12 stimulation promotes mechanical changes in the nucleus of T-ALL cells.
Fig. 5: Conventional PKC regulates CXCL12-medited H3K9 methylation in T-ALL cells.
Fig. 6: The H3K9 methyltransferases G9a and suv39h1 regulate the H3K9 methylation induced by CXCL12 in T-ALL cells.
Fig. 7: H3K9 methylation controls T-ALL chemotaxis through rigid pores in response to CXCL12.
Fig. 8: H3K9 methylation regulates nuclear constrictions and T-ALL migration in vitro and in vivo systems.

Similar content being viewed by others

References

  1. Pui CH, Robison LL, Look AT. Acute lymphoblastic leukaemia. Lancet. 2008;371:1030–43.

    Article  CAS  PubMed  Google Scholar 

  2. Aifantis I, Raetz E, Buonamici S. Molecular pathogenesis of T-cell leukemia and lymphoma. Nat Rev Immunol. 2008;8:380–90.

    Article  CAS  PubMed  Google Scholar 

  3. Pui CH, Jeha S. New therapeutic strategies for the treatment of acute lymphoblastic leukaemia. Nat Rev Drug Disco. 2007;6:149–65.

    Article  CAS  Google Scholar 

  4. Moser B, Loetscher P. Lymphocyte traffic control by chemokines. Nat Immunol. 2001;2:123–128.

    Article  CAS  PubMed  Google Scholar 

  5. Sugiyama T, Kohara H, Noda M, Nagasawa T. Maintenance of the hematopoietic stem cell pool by CXCL12-CXCR4 chemokine signaling in bone marrow stromal cell niches. Immunity. 2006;25:977–88.

    Article  CAS  PubMed  Google Scholar 

  6. de Lourdes Perim A, Amarante MK, Guembarovski RL, de Oliveira CE, Watanabe MA. CXCL12/CXCR4 axis in the pathogenesis of acute lymphoblastic leukemia (ALL): a possible therapeutic target. Cell Mol Life Sci. 2015;72:1715–23.

    Article  PubMed  Google Scholar 

  7. Pitt LA, Tikhonova AN, Hu H, Trimarchi T, King B, Gong Y, et al. CXCL12-producing vascular endothelial niches control acute T cell leukemia maintenance. Cancer Cell. 2015;27:755–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Scupoli MT, Donadelli M, Cioffi F, Rossi M, Perbellini O, Malpeli G, et al. Bone marrow stromal cells and the upregulation of interleukin-8 production in human T-cell acute lymphoblastic leukemia through the CXCL12/CXCR4 axis and the NF-kappaB and JNK/AP-1 pathways. Haematologica. 2008;93:524–32.

    Article  CAS  PubMed  Google Scholar 

  9. Cancilla D, Rettig MP, DiPersio JF. Targeting CXCR4 in AML and ALL. Front Oncol. 2020;10:1672.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Hong Z, Wei Z, Xie T, Fu L, Sun J, Zhou F, et al. Targeting chemokines for acute lymphoblastic leukemia therapy. J Hematol Oncol. 2021;14:48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Rea S, Eisenhaber F, O’Carroll D, Strahl BD, Sun ZW, Schmid M. et al. Regulation of chromatin structure by site-specific histone H3 methyltransferases. Nature. 2000;406:593–9.

    Article  CAS  PubMed  Google Scholar 

  12. Friedl P, Wolf K, Lammerding J. Nuclear mechanics during cell migration. Curr Opin Cell Biol. 2011;23:55–64.

    Article  CAS  PubMed  Google Scholar 

  13. Pfeifer CR, Irianto J, Discher DE. Nuclear mechanics and cancer cell migration. Adv Exp Med Biol. 2019;1146:117–30.

    Article  CAS  PubMed  Google Scholar 

  14. Stephens AD, Banigan EJ, Marko JF. Chromatin’s physical properties shape the nucleus and its functions. Curr Opin Cell Biol. 2019;58:76–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Schumann K, Lammermann T, Bruckner M, Legler DF, Polleux J, Spatz JP, et al. Immobilized chemokine fields and soluble chemokine gradients cooperatively shape migration patterns of dendritic cells. Immunity. 2010;32:703–13.

    Article  CAS  PubMed  Google Scholar 

  16. Nakayama J, Rice JC, Strahl BD, Allis CD, Grewal SI. Role of histone H3 lysine 9 methylation in epigenetic control of heterochromatin assembly. Science. 2001;292:110–3.

    Article  CAS  PubMed  Google Scholar 

  17. Kidiyoor GR, Li Q, Bastianello G, Bruhn C, Giovannetti I, Mohamood A, et al. ATR is essential for preservation of cell mechanics and nuclear integrity during interstitial migration. Nat Commun. 2020;11:4828.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Bendall LJ, Baraz R, Juarez J, Shen W, Bradstock KF. Defective p38 mitogen-activated protein kinase signaling impairs chemotaxic but not proliferative responses to stromal-derived factor-1alpha in acute lymphoblastic leukemia. Cancer Res. 2005;65:3290–8.

    Article  CAS  PubMed  Google Scholar 

  19. Pajerowski JD, Dahl KN, Zhong FL, Sammak PJ, Discher DE. Physical plasticity of the nucleus in stem cell differentiation. Proc Natl Acad Sci USA. 2007;104:15619–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Stephens AD, Banigan EJ, Adam SA, Goldman RD, Marko JF. Chromatin and lamin A determine two different mechanical response regimes of the cell nucleus. Mol Biol Cell. 2017;28:1984–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Le Berre M, Aubertin J, Piel M. Fine control of nuclear confinement identifies a threshold deformation leading to lamina rupture and induction of specific genes. Integr Biol (Camb). 2012;4:1406–14.

    Article  Google Scholar 

  22. Jost TR, Borga C, Radaelli E, Romagnani A, Perruzza L, Omodho L, et al. Role of CXCR4-mediated bone marrow colonization in CNS infiltration by T cell acute lymphoblastic leukemia. J Leukoc Biol. 2016;99:1077–87.

    Article  CAS  PubMed  Google Scholar 

  23. Melo RCC, Longhini AL, Bigarella CL, Baratti MO, Traina F, Favaro P. et al. CXCR7 is highly expressed in acute lymphoblastic leukemia and potentiates CXCR4 response to CXCL12. PLoS One. 2014;9:e85926

    Article  PubMed  PubMed Central  Google Scholar 

  24. Wang JF, Park IW, Groopman JE. Stromal cell-derived factor-1alpha stimulates tyrosine phosphorylation of multiple focal adhesion proteins and induces migration of hematopoietic progenitor cells: roles of phosphoinositide-3 kinase and protein kinase C. Blood. 2000;95:2505–13.

    Article  CAS  PubMed  Google Scholar 

  25. Lai YS, Chen JY, Tsai HJ, Chen TY, Hung WC. The SUV39H1 inhibitor chaetocin induces differentiation and shows synergistic cytotoxicity with other epigenetic drugs in acute myeloid leukemia cells. Blood. Cancer J. 2015;5:e313.

    Google Scholar 

  26. Lu C, Klement JD, Yang D, Albers T, Lebedyeva IO, Waller JL. et al. SUV39H1 regulates human colon carcinoma apoptosis and cell cycle to promote tumor growth. Cancer Lett. 2020;476:87–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Irianto J, Xia Y, Pfeifer CR, Greenberg RA, Discher DE. As a nucleus enters a small pore, chromatin stretches and maintains integrity, even with DNA breaks. Biophys J. 2017;112:446–9.

    Article  CAS  PubMed  Google Scholar 

  28. Vargas P, Terriac E, Lennon-Dumenil AM, Piel M. Study of cell migration in microfabricated channels. J Vis Exp. 2014;84:e51099.

    Google Scholar 

  29. Cannon JL, Oruganti SR, Vidrine DW. Molecular regulation of T-ALL cell infiltration into the CNS. Oncotarget. 2017;8:84626–7.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Frishman-Levy L, Izraeli S. Advances in understanding the pathogenesis of CNS acute lymphoblastic leukemia and potential for therapy. Br J Haematol. 2017;176:157–67.

    Article  PubMed  Google Scholar 

  31. Vadillo E, Dorantes-Acosta E, Pelayo R, Schnoor M. T cell acute lymphoblastic leukemia (T-ALL): New insights into the cellular origins and infiltration mechanisms common and unique among hematologic malignancies. Blood Rev. 2018;32:36–51.

    Article  CAS  PubMed  Google Scholar 

  32. Gomez AM, Martinez C, Gonzalez M, Luque A, Melen GJ, Martínez J, et al. Chemokines and relapses in childhood acute lymphoblastic leukemia: A role in migration and in resistance to antileukemic drugs. Blood Cells Mol Dis. 2015;55:220–7.

    Article  CAS  PubMed  Google Scholar 

  33. Bradstock KF, Makrynikola V, Bianchi A, Shen W, Hewson J, Gottlieb DJ. Effects of the chemokine stromal cell-derived factor-1 on the migration and localization of precursor-B acute lymphoblastic leukemia cells within bone marrow stromal layers. Leukemia. 2000;14:882–8.

    Article  CAS  PubMed  Google Scholar 

  34. Kato I, Niwa A, Heike T, Fujino H, Saito MK, Umeda K, et al. Identifcation of hepatic niche harboring human acute lymphoblastic leukemic cells via the SDF-1/CXCR4 axis. PLoS ONE. 2011;6:e27042.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Kuang SQ, Fang Z, Zweidler-McKay PA, Yang H, Wei Y, Gonzalez-Cervantes EA, et al. Epigenetic inactivation of Notch-Hes pathway in human B-cell acute lymphoblastic leukemia. PLoS One. 2013;8:e61807.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Crazzolara R, Kreczy A, Mann G, Heitger A, Eibl G, Fink FM. et al. High expression of the chemokine receptor CXCR4 predicts extramedullary organ infiltration in childhood acute lymphoblastic leukaemia. Br J Haematol. 2001;115:545–53.

    Article  CAS  PubMed  Google Scholar 

  37. Bao Y, Wang Z, Liu B, Lu X, Xiong Y, Shi J, et al. A feed-forward loop between nuclear translocation of CXCR4 and HIF-1alpha promotes renal cell carcinoma metastasis. Oncogene. 2019;38:881–95.

    Article  CAS  PubMed  Google Scholar 

  38. Alsadeq A, Fedders H, Vokuhl C, Belau NM, Zimmermann M, Wirbelauer T, et al. The role of ZAP70 kinase in acute lymphoblastic leukemia infiltration into the central nervous system. Haematologica. 2017;102:346–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Levoye A, Balabanian K, Baleux F, Bachelerie F, Lagane B. CXCR7 heterodimerizes with CXCR4 and regulates CXCL12-mediated G protein signaling. Blood. 2009;113:6085–93.

    Article  CAS  PubMed  Google Scholar 

  40. Song ZY, Wang F, Cui SX, Gao ZH. Qu XJ.CXCR7/CXCR4 heterodimer-induced histone demethylation: a new mechanism of colorectal tumorigenesis. Oncogene. 2019;38:1560–75.

    Article  CAS  PubMed  Google Scholar 

  41. Altman A, Kong KF. Protein kinase C enzymes in the hematopoietic and immune systems. Annu Rev Immunol. 2016;34:511–38.

    Article  CAS  PubMed  Google Scholar 

  42. Petit I, Goichberg P, Spiegel A, Peled A, Brodie C, Seger R. et al. Atypical PKC-zeta regulates SDF-1-mediated migration and development of human CD34+ progenitor cells. J Clin Invest. 2005;115:168–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Wei SY, Lin TE, Wang WL, Lee PL, Tsai MC, Chiu JJ. Protein kinase C-δ and -β coordinate flow-induced directionality and deformation of migratory human blood T-lymphocytes. J Mol Cell Biol. 2014;6:458–72.

    Article  CAS  PubMed  Google Scholar 

  44. Guinamard R, Signoret N, Ishiai M, Marsh M, Kurosaki T, Ravetch JV. B cell antigen receptor engagement inhibits stromal cell-derived factor (SDF)-1alpha chemotaxis and promotes protein kinase C (PKC)-induced internalization of CXCR4. J Exp Med. 1999;189:1461–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Velázquez-Avila M, Balandrán JC, Ramírez-Ramírez D, Velázquez-Avila M, Sandoval A, Felipe-López A, et al. High cortactin expression in B-cell acute lymphoblastic leukemia is associated with increased transendothelial migration and bone marrow relapse. Leukemia. 2019;33:1337–48.

    Article  PubMed  Google Scholar 

  46. Poli A, Ratti S, Finelli C, Mongiorgi S, Clissa C, Lonetti A, et al. Nuclear translocation of PKC-alpha is associated with cell cycle arrest and erythroid differentiation in myelodysplastic syndromes (MDSs). FASEB J. 2018;32:681–92.

    Article  CAS  PubMed  Google Scholar 

  47. Edens LJ, Dilsaver MR, Levy DL. PKC-mediated phosphorylation of nuclear lamins at a single serine residue regulates interphase nuclear size in Xenopus and mammalian cells. Mol Biol Cell. 2017;28:1389–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Esteller M. Epigenetics in cancer. N. Engl J Med. 2008;358:1148–59.

    Article  CAS  PubMed  Google Scholar 

  49. Almamun M, Levinson BT, van Swaay AC, Johnson NT, McKay SD, Arthur GL, et al. Integrated methylome and transcriptome analysis reveals novel regulatory elements in pediatric acute lymphoblastic leukemia. Epigenetics. 2015;10:882–90.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Konopleva MY, Jordan CT. Leukemia stem cells and microenvironment: biology and therapeutic targeting. J Clin Oncol. 2011;29:591–9.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Passaro D, Irigoyen M, Catherinet C, Gachet S, Da Costa C, Lasgi C, et al. CXCR4 is required for Leukemia-Initiating Cell activity in T cell acute lymphoblastic leukemia. Cancer Cell. 2015;27:769–79.

    Article  CAS  PubMed  Google Scholar 

  52. Nava MM, Miroshnikova YA, Biggs LC, Whitefield DB, Metge F, Boucas J, et al. Heterochromatin-driven nuclear softening protects the genome against mechanical stress-induced damage. Cell. 2020;181:800–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Makhija E, Jokhun DS, Shivashankar GV. Nuclear deformability and telomere dynamics are regulated by cell geometric constraints. Proc Natl Acad Sci USA. 2016;113:E32–40.

    Article  CAS  PubMed  Google Scholar 

  54. Pfeifer CR, Xia Y, Zhu K, Liu D, Irianto J, García VMM, et al. Constricted migration increases DNA damage and independently represses cell cycle. Mol Biol Cell. 2018;29:1948–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Zhang X, Cook PC, Zindy E, Williams CJ, Jowitt TA, Streuli CH, et al. Integrin alpha4beta1 controls G9a activity that regulates epigenetic changes and nuclear properties required for lymphocyte migration. Nucleic Acids Res. 2016;44:3031–44.

    Article  CAS  PubMed  Google Scholar 

  56. Gerlitz G, Bustin M. Efficient cell migration requires global chromatin condensation. J Cell Sci. 2010;123:2207–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Madrazo E, Ruano D, Abad L, Alonso-Gómez E, Sánchez-Valdepeñas C, González-Murillo A. et al. G9a Correlates with VLA-4 integrin and influences the migration of childhood acute lymphoblastic leukemia cells. Cancers (Basel). 2018;10:325

    Article  Google Scholar 

  58. Sison EA, Magoon D, Li L, Annesley CE, Romagnoli B, Douglas GJ, et al. POL5551, a novel and potent CXCR4 antagonist, enhances sensitivity to chemotherapy in pediatric ALL. Oncotarget. 2015;6:30902–18.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Randhawa S, Cho BS, Ghosh D, Sivina M, Koehrer S, Müschen M, et al. Effects of pharmacological and genetic disruption of CXCR4 chemokine receptor function in B-cell acute lymphoblastic leukaemia. Br J Haematol. 2016;174:425–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Barbieri F, Bajetto A, Thellung S, Würth R, Florio T. Drug design strategies focusing on the CXCR4/CXCR7/CXCL12 pathway in leukemia and lymphoma. Expert Opin Drug Disco. 2016;11:1093–109.

    Article  CAS  Google Scholar 

  61. Redondo-Muñoz J, García-Pardo A, Teixidó J. Molecular players in hematologic tumor cell trafficking. Front Immunol. 2019;10:156.

    Article  PubMed  PubMed Central  Google Scholar 

  62. San José-Enériz E, Agirre X, Rabal O, Vilas-Zornoza A, Sanchez-Arias JA, Miranda E, et al. Discovery of first-in-class reversible dual small molecule inhibitors against G9a and DNMTs in hematological malignancies. Nat Commun. 2017;8:15424.

    Article  PubMed  PubMed Central  Google Scholar 

  63. Dong C, Wu Y, Yao J, Wang Y, Yu Y, Rychahou PG, et al. G9a interacts with Snail and is critical for Snail-mediated E-cadherin repression in human breast cancer. J Clin Invest. 2012;122:1469–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Yokoyama M, Chiba T, Zen Y, Oshima M, Kusakabe Y, Noguchi Y, et al. Histone lysine methyltransferase G9a is a novel epigenetic target for the treatment of hepatocellular carcinoma. Oncotarget. 2017;8:21315–26.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Isham CR, Tibodeau JD, Jin W, Xu R, Timm MM, Bible KC. Chaetocin: a promising new antimyeloma agent with in vitro and in vivo activity mediated via imposition of oxidative stress. Blood. 2007;109:2579–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Jung HJ, Seo I, Casciello F, Jacquelin S, Lane SW, Suh SI, et al. The anticancer effect of chaetocin is enhanced by inhibition of autophagy. Cell Death Dis. 2016;7:e2098.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors thank the Microscopy Unit and the Flow Cytometry Core Unit of Instituto de Investigación Biosanitaria Gregorio Marañón (IiSGM) for assistance with confocal, videomicroscopy and flow cytometry analyses. The UCM-Genomic CAI Unit for their assistance with the microarray experiments. We thank Dr. Ignacio Casal, Joaquín Teixidó, Alicia García-Arroyo and María Montoya for insightful and critical comments. This research was supported by a FPI Scholarship 2018 (Ministerio de Ciencia e Innovacion/MICINN, Agencia Estatal de Investigacion/AEI y Fondo Europeo de Desarrollo Regional/FEDER) to R.G.N.; an undergraduate fellowship “Beca de Introducción a la Investigación” (Asociación Española Contra el Cáncer) to C.O.P.; and by grants from Asociación Pablo Ugarte to M.R., Gilead Sciences International Scholar in Hematology/Oncology (Gilead), 2020 Leonardo Grant for Researchers and Cultural Creators (BBVA Foundation) and SAF2017-86327-R (Ministerio de Ciencia e Innovacion/MICINN, Agencia Estatal de Investigacion/AEI y Fondo Europeo de Desarrollo Regional/FEDER) to J.R.M.

Author information

Author notes

  1. These authors contributed equally: Elena Madrazo, Raquel González-Novo.

Authors and Affiliations

  1. Department of Molecular Medicine, Centro de Investigaciones Biológicas Margarita Salas (CIB Margarita Salas-CSIC), Madrid, Spain

    Elena Madrazo, Raquel González-Novo, Cándido Ortiz-Placín & Javier Redondo-Muñoz

  2. Bioinformatics and Biostatistics Unit, Centro de Investigaciones Biológicas Margarita Salas (CIB Margarita Salas-CSIC), Madrid, Spain

    Mario García de Lacoba

  3. Department of Paediatric Haematology & Oncology, Hospital Universitario Niño Jesús, Madrid, Spain

    África González-Murillo & Manuel Ramírez

  4. Health Research Institute La Princesa, Madrid, Spain

    África González-Murillo & Manuel Ramírez

Authors
  1. Elena Madrazo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Raquel González-Novo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Cándido Ortiz-Placín
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mario García de Lacoba
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. África González-Murillo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Manuel Ramírez
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Javier Redondo-Muñoz
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

EM carried out biochemical and imaging experiments and contributed to the interpretation of biological data. RGN performed biochemical and in vivo studies. COP contributed to biochemical and imaging experiments. AGM provided clinically annotated multiple ALL samples and contributed to in vivo experiments and the interpretation of clinical data. MGL carried out the bioinformatics analysis of ChIP-seq and microarray data samples and contributed to the interpretation of data. MR designed part of the studies, provided ALL samples, and contributed to the interpretation of clinical data. JRM designed the studies, supervised the project, and wrote the manuscript with the input of all authors.

Corresponding author

Correspondence to Javier Redondo-Muñoz.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Madrazo, E., González-Novo, R., Ortiz-Placín, C. et al. Fast H3K9 methylation promoted by CXCL12 contributes to nuclear changes and invasiveness of T-acute lymphoblastic leukemia cells. Oncogene 41, 1324–1336 (2022). https://doi.org/10.1038/s41388-021-02168-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41388-021-02168-8

  • Springer Nature Limited

This article is cited by

Search

Navigation