PLX281833

GSE129244: Ldb1 is required for Lmo2 oncogene-induced thymocyte self-renewal and T-cell Acute Lymphoblastic Leukemia

• Organsim mouse
• Type RNASEQ
• Target gene
• Project ARCHS4

Prolonged or enhanced expression of the proto-oncogene Lmo2 is associated with a severe form of T-cell Acute Lymphoblastic Leukemia (T-ALL), designated Early T-progenitor ALL (ETP-ALL), that is characterized by the aberrant self-renewal and subsequent oncogenic transformation of immature thymocytes. Recent data suggest that Lmo2 may exert these effects by functioning as component of a multi-subunit transcription complex that includes the ubiquitous adapter Ldb1 along with b-HLH and/or GATA family transcription factors. In this study, we investigated the importance of Ldb1 for Lmo2-induced T-ALL by conditional deletion of Ldb1 in thymocytes in a Lmo2 transgenic mouse model of T-ALL. Our results identify a critical requirement for Ldb1 in the induction of thymocyte self-renewal, thymocyte radio-resistance and transition to T-ALL in Lmo2 transgenic mice. Ldb1 was also required for acquisition of the pre-leukemic ETP gene expression signature in immature Lmo2 transgenic thymocytes. Together, these results support a model where Lmo2-induced T-ALL results from failure to down-regulate Ldb/Lmo2 nucleated transcription complexes that normally function to enforce self-renewal in bone marrow hematopoietic progenitors SOURCE: Apratim Mitra (apratim.mitra@nih.gov) - Section on Genomic Imprinting NICHD