Abstract
Patient-derived induced pluripotent stem cells (iPSCs) have recently provided a new way to model acute myeloid leukemia (AML) and other myeloid malignancies. Here, we describe methods for the generation of patient-derived iPSCs from leukemia cells and for their subsequent directed in vitro differentiation into hematopoietic cells that recapitulate features of leukemia stem cells (LSCs) and leukemic blasts.
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References
Takahashi K, Yamanaka S (2006) Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126(4):663–676
Takahashi K, Tanabe K, Ohnuki M et al (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131(5):861–872
Park IH, Arora N, Huo H et al (2008) Disease-specific induced pluripotent stem cells. Cell 134(5):877–886
Raya A, Rodriguez-Piza I, Guenechea G et al (2009) Disease-corrected haematopoietic progenitors from Fanconi anaemia induced pluripotent stem cells. Nature 460(7251):53–59
Batista LF, Pech MF, Zhong FL et al (2011) Telomere shortening and loss of self-renewal in dyskeratosis congenita induced pluripotent stem cells. Nature 474(7351):399–402
Papapetrou EP, Lee G, Malani N et al (2011) Genomic safe harbors permit high beta-globin transgene expression in thalassemia induced pluripotent stem cells. Nat Biotechnol 29(1):73–78
Amabile G, Welner RS, Nombela-Arrieta C et al (2013) In vivo generation of transplantable human hematopoietic cells from induced pluripotent stem cells. Blood 121(8):1255–1264
Kumano K, Arai S, Hosoi M et al (2012) Generation of induced pluripotent stem cells from primary chronic myelogenous leukemia patient samples. Blood 119(26):6234–6242
Ye Z, Zhan H, Mali P et al (2009) Human-induced pluripotent stem cells from blood cells of healthy donors and patients with acquired blood disorders. Blood 114(27):5473–5480
Hosoi M, Kumano K, Taoka K et al (2014) Generation of induced pluripotent stem cells derived from primary and secondary myelofibrosis patient samples. Exp Hematol 42(9):816–825
Kotini AG, Chang CJ, Boussaad I et al (2015) Functional analysis of a chromosomal deletion associated with myelodysplastic syndromes using isogenic human induced pluripotent stem cells. Nat Biotechnol 33(6):646–655
Chao MP, Gentles AJ, Chatterjee S et al (2017) Human AML-iPSCs reacquire leukemic properties after differentiation and model clonal variation of disease. Cell Stem Cell 20(3):329–344. e327
Kotini AG, Chang CJ, Chow A et al (2017) Stage-specific human induced pluripotent stem cells map the progression of myeloid transformation to transplantable leukemia. Cell Stem Cell 20(3):315–328 e317
Chang CJ, Kotini AG, Olszewska M et al (2018) Dissecting the contributions of cooperating gene mutations to cancer phenotypes and drug responses with patient-derived iPSCs. Stem Cell Rep 10(5):1610–1624
Papapetrou EP, Sadelain M (2011) Generation of transgene-free human induced pluripotent stem cells with an excisable single polycistronic vector. Nat Protoc 6(9):1251–1273
Acknowledgments
The authors thank all members of the Papapetrou lab for their contributions to the development and refinement of the experimental protocols described here. This work was supported by NIH grants R01HL121570, R01HL137219, R01CA225231, and R01 HL132071 and by the Edward P. Evans Foundation, the New York State Stem Cell Science Board (NYSTEM), the Henry and Marilyn Taub Foundation, the Alex’s Lemonade Stand Foundation, the RUNX1 research program, the Pershing Square Sohn Cancer Research Alliance, and the Leukemia and Lymphoma Society.
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Deslauriers, A.G., Kotini, A.G., Papapetrou, E.P. (2021). Modeling Leukemia Stem Cells with Patient-Derived Induced Pluripotent Stem Cells. In: Cobaleda, C., Sánchez-García, I. (eds) Leukemia Stem Cells. Methods in Molecular Biology, vol 2185. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-0810-4_26
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DOI: https://doi.org/10.1007/978-1-0716-0810-4_26
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Publisher Name: Humana, New York, NY
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Online ISBN: 978-1-0716-0810-4
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