Modeling of Chronic Myeloid Leukemia: An Overview of In Vivo Murine and Human Xenograft Models

Abstract

Over the past years, a wide variety of in vivo mouse models have been generated in order to unravel the molecular pathology of Chronic Myeloid Leukemia (CML) and to develop and improve therapeutic approaches. These models range from (conditional) transgenic models, knock-in models, and murine bone marrow retroviral transduction models followed by transplantation. With the advancement of immunodeficient xenograft models, it has become possible to use human stem/progenitor cells for in vivo studies as well as cells directly derived from CML patients. These models not only mimic CML but also have been instrumental in uncovering various fundamental mechanisms of CML disease progression and tyrosine kinase inhibitor (TKI) resistance. With the availability of iPSC technology, it has become feasible to derive, maintain, and expand CML subclones that are at least genetically identical to those in patients. The following review provides an overview of all murine as well as human xenograft models for CML established till date.

Calcium influx, oxidative stress, and apoptosis induced by TRPV1 in chronic myeloid leukemia cells: Synergistic effects with imatinib

“…Thus, to bridge the gaps, our future direction is to confirm our results by using both blood collected from CML patients stratified according to TKI resistance and mouse models of CML. In recent years, several in vivo models of CML have been established, by using chimeric mouse strains as well as different immunocompromised strains ( Sontakke et al, 2016 ), to study the molecular pathogenesis of the disease and approach new therapeutic strategies. Thus, transgenic, conditioned, and/or xenograft mice CML models can be used to validate the effects of TRPV1 activation triggered by OLDA.…”

Studying Side Effects of Tyrosine Kinase Inhibitors in a Juvenile Rat Model with Focus on Skeletal Remodeling

“…The aim of the animal model described in this chapter was to evaluate side effects on bone remodeling rather than gaining further insight into the biology of CML (e.g., to study elementary mechanisms of CML disease progression) or on a more efficient antileukemic treatment exerted by new drugs (e.g., exploring why resistance develops under TKI therapy) [114,115]. For these essential questions, the reader is kindly referred to the detailed body of literature on establishing and maintaining acute lymphatic or myeloid leukemic cells in xenograft models, transgenic models, and syngeneic models using a broad range of species [116][117][118][119], whereas mice are used mostly in orthotopic animal models [120][121][122][123].…”

Prognostic Significance of Early Molecular Response in Patients Diagnosed with Chronic Myeloid Leukemia in Chronic Phase Treated with Nilotinib as a First-Line Therapy

“…Chronic Myeloid Leukaemia (CML) is the paradigm of bench-to-bedside translational research (7) One of the rst cancers to be de nitively linked to a genetic mutation, the Philadelphia Chromosome, which produces the chimeric BCR-ABL protein, was CML. Numerous investigations using cellular and murine models (21) all agreed that the oncogenic gene BCR-ABL can generate a strong leukaemogenic signal. (17) Tyrosine kinase inhibitors (TKIs) that target BCR-ABL have been the main treatment for CML since their appearance in 2001.…”