While activating mutations of NOTCH1 are observed in most T-ALL cases, these mutations alone are not sufficient to drive the full development of T-ALL.
To directly explore whether IL-7R targeting may be therapeutically efficient against T-ALL relapse, we focused on a known Notch1-induced T-ALL model, because a majority of T-ALL patients harbor activating mutations in NOTCH1, which is a transcriptional regulator of IL-7R expression.
Since more than 60% of T-ALL cases bear oncogenic NOTCH1 mutations, small molecule inhibitors of NOTCH1 signalling; γ-secretase inhibitors (GSI), are being actively investigated for the treatment of T-ALL.
Testing of Notch1-targeting therapeutic antibodies demonstrated T-ALL sensitivity to different classes of Notch1 blockers based on Notch1 mutational status.
To investigate the prognostic value of NOTCH1 associated with lncRNA in T cell acute lymphoblastic leukemia 1 (NALT1) in GC and the mechanism of its involvement in GC invasion and metastasis.
Despite the limitations of having a small sample size and a non-minimal residual disease-based protocol, our results suggest that the presence of NOTCH1 mutations might contribute to the disease relapse of T-ALL.
Consistent with a leukemia-initiating tumor suppressor role, inactivation of <i>Phf6</i> in hematopoietic progenitors lowers the threshold for the development of NOTCH1-induced T-ALL.
The identification of activating mutations in NOTCH1 in 50% of T cell acute lymphoblastic leukemia has generated interest in elucidating how these mutations contribute to oncogenic transformation and in targeting the pathway.
Then, cells from each population were retrovirally transduced to initiate MLL-AF9 acute myelogenous leukemia (AML) and the intracellular domain of NOTCH-1T-cell acute lymphoblastic leukemia (T-ALL).
Overall our findings indicate JMJD3 and p300 as general Notch1 and Notch3 signaling co-activators in T-ALL and suggest further investigation on the potential therapeutic anti-leukemic efficacy of their enzymatic inhibition in Notch/c-Myc axis-related cancers and diseases.
The nuclear expression of NOTCH1 protein was detected in 25% and 5% of cases of T-ALL/LBL and CLL/SLL, respectively, whereas cytoplasmic expression was detected in 33.3% and 15% cases, respectively.
Here, using the TEL-JAK2 transgenic (TJ2-Tg) mouse model of T-ALL/LBL, which is driven by constitutive JAK/STAT signaling and characterized by the acquisition of Notch1 mutations, we sought to identify stromal cell alterations associated with thymic leukemogenesis.
In an established model of Notch1-driven T-cell acute lymphoblastic leukemia (T-ALL), MBD2 ablation impeded malignant progression and maintenance by attenuating the Wnt signaling pathway.
Notably, CD44 is shown to support crucial BM niche interactions necessary for LIC activity of human T-ALL xenografts and disease progression, highlighting the importance of the NOTCH1/CD44 axis in T-ALL pathogenesis.
NOTCH1/FBXW7 mutations trigger oncogenic NOTCH1 signaling and its downstream target genes play crucial roles in the molecular pathogenesis of T-cell acute lymphoblastic leukemia (T-ALL).
The SERCA (sarco-endoplasmic reticulum Ca<sup>2+</sup> ATPase) inhibitor thapsigargin inhibits mutant NOTCH1 receptors compared with wild type in T cell acute lymphoblastic leukemia (T-ALL), but its administration is predicted to be toxic in humans.