Abstract
Chronic myeloid leukemia (CML) is a myeloproliferative disorder with a high number of well-differentiated neutrophils in peripheral blood and myeloid cells in bone marrow (BM). CML is derived from the hematopoietic stem cells (HSCs) with the Philadelphia chromosome (Ph+, t(9;22)-(q34;q11)), resulting in generating a fusion oncogene, BCR/ABL1. HSCs with Ph+ are defined as leukemia stem cells (LSCs), a subpopulation cell at the apex of hierarchies in leukemia cells and responsible for the disease continuous propagation. Several kinds of CML models have been developed to reveal the mechanism of CML pathogenesis and evaluate therapeutic drugs in the past three decades. Here, we describe the procedures to generate a CML mouse model by introducing BCR/ABL1 into Lin−Sca1+ cKit+ population cells purified from mouse bone marrow. In CML retroviral transduction/transplantation mouse models, this modified model can mimic CML pathogenesis on high fidelity.
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References
Kurzrock R, Kantarjian HM, Druker BJ, Talpaz M (2003) Philadelphia chromosome-positive leukemias: from basic mechanisms to molecular therapeutics. Ann Intern Med 138:819–830
Fialkow PJ, Denman AM, Jacobson RJ, Lowenthal MN (1978) Chronic myelocytic leukemia. Origin of some lymphocytes from leukemic stem cells. J Clin Invest 62:815–823
O’Hare T, Zabriskie MS, Eiring AM, Deininger MW (2012) Pushing the limits of targeted therapy in chronic myeloid leukaemia. Nat Rev Cancer 12:513–526
Lane SW, Gilliland DG (2010) Leukemia stem cells. Semin Cancer Biol 20:71–76
Hu Y, Swerdlow S, Duffy TM, Weinmann R, Lee FY, Li S (2006) Targeting multiple kinase pathways in leukemic progenitors and stem cells is essential for improved treatment of Ph + leukemia in mice. Proc Natl Acad Sci U S A 103:16870–16875
Eisterer W, Jiang X, Christ O, Glimm H, Lee KH, Pang E, Lambie K, Shaw G, Holyoake TL, Petzer AL, Auewarakul C, Barnett MJ, Eaves CJ, Eaves AC (2005) Different subsets of primary chronic myeloid leukemia stem cells engraft immunodeficient mice and produce a model of the human disease. Leukemia 19:435–441
Bhatia M, Wang JC, Kapp U, Bonnet D, Dick JE (1997) Purification of primitive human hematopoietic cells capable of repopulating immune-deficient mice. Proc Natl Acad Sci U S A 94:5320–5325
Herrmann H, Sadovnik I, Cerny-Reiterer S, Rulicke T, Stefanzl G, Willmann M, Hoermann G, Bilban M, Blatt K, Herndlhofer S, Mayerhofer M, Streubel B, Sperr WR, Holyoake TL, Mannhalter C, Valent P (2014) Dipeptidylpeptidase IV (CD26) defines leukemic stem cells (LSC) in chronic myeloid leukemia. Blood 123:3951–3962
Van Etten RA (2001) Models of chronic myeloid leukemia. Curr Oncol Rep 3:228–237
Ilaria RL Jr (2004) Animal models of chronic myelogenous leukemia. Hematol Oncol Clin North Am 18:525–543, vii
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Hu, Y. (2016). CML Mouse Model Generated from Leukemia Stem Cells. In: Li, S., Zhang, H. (eds) Chronic Myeloid Leukemia. Methods in Molecular Biology, vol 1465. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-4011-0_3
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DOI: https://doi.org/10.1007/978-1-4939-4011-0_3
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Publisher Name: Humana Press, New York, NY
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Online ISBN: 978-1-4939-4011-0
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