Transient responses to NOTCH and TLX1/HOX11 inhibition in T-cell acute lymphoblastic leukemia/lymphoma.

ABSTRACT: To improve the treatment strategies of T-cell acute lymphoblastic leukemia/lymphoma (T-ALL), further efforts are needed to identify therapeutic targets. Dysregulated expression of HOX-type transcription factors occurs in 30-40% of cases of T-ALL. TLX1/HOX11 is the prototypical HOX-type transcription factor. TLX1 may be an attractive therapeutic target because mice that are deficient in TLX1 are healthy. To test this possibility, we developed a conditional doxycycline-regulated mouse model of TLX1-initiated T-ALL. TLX1 induced T-ALL after ∼5-7 months with penetrance of 15-60%. Similar to human TLX1-type T-ALLs, the TLX1-induced tumors were arrested at the cortical stage of T-cell development and acquired activating NOTCH1 mutations. Inhibition of NOTCH signaling abrogated growth of cell lin

SUBMITTER: Rakowski LA 

PROVIDER: S-EPMC3033898 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature