Mouse Models of CMML

Abstract

Chronic myelomonocytic leukemia (CMML) is a rare and challenging type of myeloproliferative neoplasm. Poor prognosis and high mortality, associated predominantly with progression to secondary acute myeloid leukemia (sAML), is still an unsolved problem. Despite a growing body of knowledge about the molecular repertoire of this disease, at present, the prognostic significance of CMML-associated mutations is controversial. The absence of available CMML cell lines and the small number of patients with CMML make pre-clinical testing and clinical trials complicated. Currently, specific therapy for CMML has not been approved; most of the currently available therapeutic approaches are based on myelodysplastic syndrome (MDS) and other myeloproliferative neoplasm (MNP) studies. In this regard, the development of the robust CMML animal models is currently the focus of interest. This review describes important studies concerning animal models of CMML, examples of methodological approaches, and the obtained hematologic phenotypes.

Real-World Data on Chronic Myelomonocytic Leukemia: Clinical and Molecular Characteristics, Treatment, Emerging Drugs, and Patient Outcomes

“…Comprehensive information about clonal evolution from CMML to AML is still lacking. A few sequential studies comparing paired patient samples at the time of CMML diagnosis and at AML transformation have postulated a key role for the RAS pathway and for mutations in EZH2, IDH1/2, NPM1 , and FLT3 -ITD [ 14 , 50 ]. Patel et al [ 16 ] suggested that TET2, ASXL1 , and SRSF2 were ancestral mutations present in early stages of CMML and that KRAS, NRAS, RUNX1, U2AF1 , and CBL mutations were secondary events leading to AML transformation.…”

In Vitro and In Vivo Modeling of Normal and Leukemic Bone Marrow Niches: Cellular Senescence Contribution to Leukemia Induction and Progression

“…Even though animal models are valuable tools for research, the expenditure is high, drug screening requires a large amount of animals and, biologically, model animals cannot completely mimic human BM microenvironments. These issues emphasize the need for better strategies to improve human systems modeling in vivo; in this context, new results and extensive reviews regarding animal models for leukemic research are periodically published [127,129,[136][137][138][139][140][141][142][143][144][145][146]. The graph is based on [129], with additional information from [145,[147][148][149].…”