title: Chronic Myeloid Leukemia (CML) Mouse Model in Translational Research.
abstract: Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by increased proliferation of granulocytic cells without the loss of their capability to differentiate. CML is a clonal disease, originated at the level of Hematopoietic Stem Cells with the Philadelphia chromosome resulting from a reciprocal translocation between the chromosomes 9 and 22t(9;22)-(q34;q11). This translocation produces a fusion gene known as BCR-ABL which acquires uncontrolled tyrosine kinase activity, constantly turning on its downstream signaling molecules/pathways, and promoting proliferation of leukemia cell through anti-apoptosis and acquisition of additional mutations. To evaluate the role of each critical downstream signaling molecule of BCR-ABL and test therapeutic drugs in vivo, it is important to use physiological mouse disease models. Here, we describe a mouse model of CML induced by BCR-ABL retrovirus (MSCV-BCR-ABL-GFP; MIG-BCR-ABL) and how to use this model in translational research.Moreover, to expand the application of this retrovirus induced CML model in a lot of conditional knockout mouse strain, we modified this vector to a triple gene coexpression vector in which we can co-express BCR-ABL, GFP, and a third gene which will be tested in different systems. To apply this triple gene system in conditional gene knockout strains, we can validate the CML development in the knockout mice and trace the leukemia cell following the GFP marker. In this protocol, we also describe how we utilize this triple gene system to prove the function of Pten as a tumor suppressor in leukemogenesis. Overall, this triple gene system expands our research spectrum in current conditional gene knockout strains and benefits our CML translational research.
authors.affiliation: School of Dental Medicine, Tufts University, 1 Kneeland Street, Boston, 02111, MA, USA.
authors.forename: Cong
authors.initials: C
authors.lastname: Peng
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA, 01605, USA. shaoguang.li@umassmed.edu.
authors.forename: Shaoguang
authors.initials: S
authors.lastname: Li
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D016044:Fusion Proteins, bcr-abl / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D047428:Protein Kinase Inhibitors; D012190:Retroviridae / Q000235:genetics; D015398:Signal Transduction; D057170:Translational Research, Biomedical / Q000379:methods*
chemical_list: D047428:Protein Kinase Inhibitors; D016044:Fusion Proteins, bcr-abl
keywords: BCR-ABL; Chronic myeloid leukemia (CML); Hematopoietic stem cell; Philadelphia chromosome (Ph+ chromosome); Retroviral mouse model; Translational research