19Aug 2023
TAL1 hijacks MYCN enhancer that induces MYCN expression and dependence on mevalonate pathway in T-cell acute lymphoblastic leukemia

TAL1 hijacks MYCN enhancer that induces MYCN expression and dependence on mevalonate pathway in T-cell acute lymphoblastic leukemia

T-cell acute lymphoblastic leukemia (T-ALL) is characterized by abnormal expression of oncogenic transcription factors (TFs) like TAL1, NOTCH1, and MYC, disrupting gene regulation. The study revealed a conserved enhancer (enhMYCN) activated by TAL1, crucial for MYCN oncogene expression in T-ALL cells. TAL1-positive T-ALL cells depend on MYCN for survival and exhibit sensitivity to HMGCR inhibition. Both MYCN and MYC regulate similar genes, creating a dual dependency in TAL1-MYCN and NOTCH1-MYC pathways. Targeting the TAL1-MYCN-HMGCR axis could be a potential T-ALL therapy.

  • #oncology

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