NOTCH1-Induced T-Cell Acute Lymphoblastic Leukemia In Vivo Models

Methods Mol Biol. 2024;2773:9-24. doi: 10.1007/978-1-0716-3714-2_2.

ABSTRACT

T-cell acute lymphoblastic leukemia (T-ALL) is primarily a NOTCH1-driven disease, which represents approximately 15% of pediatric and 25% of adult newly diagnosed ALL cases. Gain-of-function NOTCH1 mutations are highly prevalent in T-ALL contributing to almost 60% of the cases. The protocol presented here describes a method for in vivo T-ALL transformation driven by the retroviral transduction of hematopoietic progenitors with oncogenic mutant forms NOTCH1 and subsequent transplant into recipient mice. This T-ALL transformation model allows the interaction between the leukemia cells and the bone marrow microenvironment, better recapitulating the physiological conditions that promote the development of the human disease, providing a versatile tool for both experimental therapeutics and functional genetics studies on T-ALL.

PMID:38236532 | DOI:10.1007/978-1-0716-3714-2_2