LMO2 overexpression

We also showed that MYB is a dependency factor in T-ALL since RNA interference of Myb blocked cell cycle progression and induced apoptosis in both human and murine T-ALL cell lines. Finally, we provide preclinical evidence that targeting the transcriptional activity of MYB can be a useful therapeutic strategy for the treatment of T-ALL.

LMO2 ISH by RNAscope method is reliable and can be applied in routine FFPE samples. Our series had good correlation with LMO2 gene expression and LMO2 IHC. Moreover, the prognostic impact on survival captured by LMO2 RNA ISH was similar to published for gene expression and IHC methods.

By generating multiple models of SOX11 expression in the T-cell lineage, we showed that SOX11 impacts T-cell differentiation, both in mice and humans, and that it can promote or hinder T-ALL formation depending on the oncogenic driver.

In LDB1-deficient AML cell lines, the overexpression of LMO2 partially compensates for the proliferation inhibition. In summary, our findings revealed that LDB1 played an important role in AML as an oncogene, and emphasize the potential importance of the LMO2/LDB1 complex in clinical treatment of patients with AML.

Finally, the combination of fluzoparib and cisplatin exhibited significant synergistic effects both in vitro and in vivo . In summary, we found that PARPis exerted an anti-lymphoma effect in NKTCL, and the underlying mechanisms may be "synthetic lethality-like" via LMO2 expression. Moreover, LMO2 may be a novel indicator for drug sensitivity and prognosis in NKTCL. These findings offer a foundation for the clinical application of PARPis and provide certain implications for the clinical management of NKTCL.

Genomic analyses revealed the presence of Notch1 mutations in pre-LSCs before subsequent loss of tumor suppressors promotes the transition to overt leukemogenesis. These studies demonstrate a critical role for impaired cell competition in the development of pre-LSCs in a transgenic mouse model of T cell acute lymphoblastic leukemia (T-ALL), implying that this process plays a role in the ontogeny of human T-ALL.

The paucity of data regarding infantile T-ALL’s clinical presentation, management, genomics, and outcomes results in difficult treatment decisions including potential use of agents such as Nelarabine, at a young age... We report a unique case of infantile T-ALL, treated initially per COG protocol AALL0631. With CSF3Rmutations association to GCSF, being an unusual finding. Additionally, LMO2 overexpression is a common driver of T-Cell malignancies, however, has not been reported in infantile T-ALL.