TLX1 mouse model recapitulates clinical symptoms of T cell acute lymphoblastic leukemia

This technology is a mouse model expressing the human oncogene T cell leukemia homeobox protein-1 (TLX1), which mimics the genetic and molecular signatures of T cell acute lymphoblastic leukemia (T-ALL).

Unmet Need: In vivo model of T cell acute lymphoblastic leukemia (T-ALL)

TLX1 has been known to have a central role in the development and progression of T cell acute lymphoblastic leukemia (T-ALL). However, a genetic and molecular dissection of pathogenesis onset and downstream targets of TLX1 have remained unknown. This is because T-ALL affects T lymphocytes and is characterized by invasion of these cells into other tissues and organs, eventually leading to tumor formation. This type of disease progression is difficult to replicate and study with cells in vitro.

The Technology: Clinical presentation of T-ALL in humans seen in a TLX1 mouse model

This technology presents a transgenic mouse expressing the human TLX1 gene. The human TLX1 is located downstream of the mouse T cell–specific p56^Lck proximal promoter. This mouse model recapitulates the development and timing of lymphoid tumors seen in humans diagnosed with T cell acute lymphoblastic leukemia (T-ALL). This mouse model allowed the identification of molecular interactors with TLX1, such as BCL11B, and of cooperating mutations in T-ALL pathogenesis onset. Overall, this mouse model replicates all known clinical signs of T-ALL in a living organism.

This technology has been validated in vivo.

Applications:

• Studying the mechanisms of T-ALL pathogenesis
• Research tool for analysis of tumor microenvironment
• Research tool for analysis of tumor suppressing agents
• Diagnostic assays for cancers
• Drug screening
• Genetic screening of cancerous mutations

Advantages:

• Replicates onset and progression of T-ALL
• Easy tumor dissection and recovery
• Recovery of cancerous cells for downstream usage
• Easy monitoring of drug effects on behavior
• Mouse model can easily be cross-bred

Lead Inventor:

Adolfo Ferrando, M.D., Ph.D.

Related Publications:

• De Keersmaecker K, Real PJ, Gatta GD, Palomero T, Sulis ML, Tosello V, Van Vlierberghe P, Barnes K, Castillo M, Sole X, Hadler M, Lenz J, Aplan PD, Kelliher M, Kee BL, Pandolfi PP, Kappes D, Gounari F, Petrie H, Van der Meulen J, Speleman F, Paietta E, Racevskis J, Wiernik PH, Rowe JM, Soulier J, Avran D, Cavé H, Dastugue N, Raimondi S, Meijerink JP, Cordon-Cardo C, Califano A, Ferrando AA. “The TLX1 oncogene drives aneuploidy in T cell transformation.” Nat Med. 2010 Nov; 16(11): 1321-7

Tech Ventures Reference:

• IR CU23147

• Licensing Contact: Joan Martinez