CRISPR/Cas9-edited NSG mice as PDX models of human leukemia to address the role of niche-derived SPARC

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  1. 1

    Cosgun KN, Rahmig S, Mende N, Reinke S, Hauber I, Schafer C et al. Kit regulates HSC engraftment across the human-mouse species barrier. Cell Stem Cell 2014; 15: 227–238.

  2. 2

    Hawkins ED, Duarte D, Akinduro O, Khorshed RA, Passaro D, Nowicka M et al. T-cell acute leukaemia exhibits dynamic interactions with bone marrow microenvironments. Nature 2016; 538: 518–522.

  3. 3

    McIntosh BE, Brown ME, Duffin BM, Maufort JP, Vereide DT, Slukvin II et al. Nonirradiated NOD,B6.SCID Il2rgamma-/- Kit(W41/W41) (NBSGW) mice support multilineage engraftment of human hematopoietic cells. Stem Cell Rep 2015; 4: 171–180.

  4. 4

    Passaro D, Di Tullio A, Abarrategi A, Rouault-Pierre K, Foster K, Ariza-McNaughton L et al. Increased vascular permeability in the bone marrow microenvironment contributes to disease progression and drug response in acute myeloid leukemia. Cancer Cell 2017; 32: 324–341 e326.

  5. 5

    Tai IT, Tang MJ . SPARC in cancer biology: its role in cancer progression and potential for therapy. Drug Resist Updat 2008; 11: 231–246.

  6. 6

    Alachkar H, Santhanam R, Maharry K, Metzeler KH, Huang X, Kohlschmidt J et al. SPARC promotes leukemic cell growth and predicts acute myeloid leukemia outcome. J Clin Invest 2014; 124: 1512–1524.

  7. 7

    DiMartino JF, Lacayo NJ, Varadi M, Li L, Saraiya C, Ravindranath Y et al. Low or absent SPARC expression in acute myeloid leukemia with MLL rearrangements is associated with sensitivity to growth inhibition by exogenous SPARC protein. Leukemia 2006; 20: 426–432.

  8. 8

    Sander JD, Joung JK . CRISPR-Cas systems for editing, regulating and targeting genomes. Nat Biotechnol 2014; 32: 347–355.

  9. 9

    Wang H, Yang H, Shivalila CS, Dawlaty MM, Cheng AW, Zhang F et al. One-step generation of mice carrying mutations in multiple genes by CRISPR/Cas-mediated genome engineering. Cell 2013; 153: 910–918.

  10. 10

    Sweeney CL, Choi U, Liu C, Koontz S, Ha SK, Malech HL . CRISPR-mediated knockout of Cybb in NSG mice establishes a model of chronic granulomatous disease for human stem-cell gene therapy transplants. Hum Gene Ther 2017; 28: 565–575.

  11. 11

    Gilmour DT, Lyon GJ, Carlton MB, Sanes JR, Cunningham JM, Anderson JR et al. Mice deficient for the secreted glycoprotein SPARC/osteonectin/BM40 develop normally but show severe age-onset cataract formation and disruption of the lens. EMBO J 1998; 17: 1860–1870.

  12. 12

    Meyer PN, Fu K, Greiner T, Smith L, Delabie J, Gascoyne R et al. The stromal cell marker SPARC predicts for survival in patients with diffuse large B-cell lymphoma treated with rituximab. Am J Clin Pathol 2011; 135: 54–61.

  13. 13

    Chow YP, Alias H, Jamal R . Meta-analysis of gene expression in relapsed childhood B-acute lymphoblastic leukemia. BMC Cancer 2017; 17: 120.

  14. 14

    Ebinger S, Ozdemir EZ, Ziegenhain C, Tiedt S, Castro Alves C, Grunert M et al. Characterization of rare, dormant, and therapy-resistant cells in acute lymphoblastic leukemia. Cancer Cell 2016; 30: 849–862.

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We thank Dr Henner Farin and Dr Michael Milsom for helpful discussions, Maresa Weitmann for technical help and Dr Michaela Socher, Dr Boris Brill and all members of the DKFZ and GSH Laboratory Animal Core Facility for excellent animal welfare and husbandry. We thank Dr Sebastian Wagner and Dr Khalil Abou Elaradat from the Frankfurt DKTK sequencing facility for the MiSeq runs and Dr Stefan Stein for the THP-1 line. We thank H Altmann and C Röllig from the SAL biobank (Dresden) and Dr Vick Binje from the Helmholtz Center (Munich) for providing samples. HM is supported by the European Research Council (ERC Grant No. 639795) and the German José Carreras Leukemia Foundation (Award No. DJCLS A 14/01).

Author contributions

IT-G, AN, EC, DS, EB, AC and HM performed experiments. AM performed the analysis of NGS data. UK and FVdH isolated the NSG zygotes and performed the cytoplasmic microinjections. IJ, JPB and UP contributed reagents and discussed results. HM designed and supervised the study. HM and ITG wrote the manuscript.

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Correspondence to H Medyouf.

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The authors declare no conflict of interest.

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Supplementary Information accompanies this paper on the Leukemia website

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Tirado-Gonzalez, I., Czlonka, E., Nevmerzhitskaya, A. et al. CRISPR/Cas9-edited NSG mice as PDX models of human leukemia to address the role of niche-derived SPARC. Leukemia 32, 1048–1051 (2018) doi:10.1038/leu.2017.346

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