Mouse models to study genes involved in hematological malignancies

Abstract

Hematological malignancies, including leukemia and lymphoma, consist a group of highly heterogeneous neoplasms characterized by numerous genetic lesions specific for the type of the disease. In order to understand, the role of a particular alteration in the development of a malignancy functional studies have to be carried out in vitro, in cell lines derived from primary cancer cells. Further efforts to understand the mechanisms underlying blood disorders including malignant transformation and progression relies on model organism research. Numerous transgenic mouse models, carrying human oncogenes have been generated resembling distinct types of hematological disorders. Recent technological advances revolutionized the generation of animal models making it much easier, faster, and precise. The introduction of the CRISPR-Cas9 technology allows for rapid generation of novel knockout or transgenic animals, and the development of conditional site- and time-specific Cre-Lox gene targeting technology, allows studying the function of genes which are relevant to normal hematopoiesis and development of hematological malignancies, but lethal when knocked out in embryonic cells. Besides the studies on gene function, mouse models of human leukemia allow for discovery and testing of novel antileukemic drugs. These new technologies are deepening our understanding of disease pathophysiology and treatment resistance, as well as are leading to novel therapeutic strategies for improved outcomes in patients.