SOX11 Functions As an Oncogene in Lmo2-Driven T-Cell Lymphoblastic Leukemia (T-ALL)

Background: T-lineage acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignancy that accounts for 10%-15% of pediatric and 25% of adult ALL cases. Although the prognosis of T-ALL has been improving over time, the outcome of T- ALL patients with primary resistant or relapsed leukemia remains poor. Thus, further advances in the treatment of T-ALL require the identification of new targets for the development of highly specific molecularly targeted drugs. SRY-related HMG-box 11 (SOX11) is a member of the SOXC family, which also includes SOX4 and SOX12. SOX11 is single-exon gene that encodes a transcription factor, but its molecular properties and functions remain incompletely understood. Expression of SOX11 is strongly associated with neurogenic activity, and it is confined to the central nervous system. Aberrant SOX11 upregulation has been observed in several cancer types, such as medulloblastoma, glioma, and B- and T-cell lymphomas. Under physiological conditions, SOX11 is absent in the T-cell lineage. However, SOX11 expression is consistently found in a subset of TAL/LMO T-ALL cases characterized by an abundancy of PTEN mutations and an underrepresentation of NOTCH mutations. Since the expression of SOX11 is restricted to a malignant context, we postulate that SOX11 might act as an oncogene in T-ALL.