DLK1 is a GATA1s-Driven Dependency

In this study, we identified DLK1 – a fetal hematopoietic protein and direct GATA1s target – as a leukemia dependency in ML-DS. DLK1 is highly expressed in fetal progenitors but absent in normal adult hematopoiesis, making it a uniquely attractive therapeutic target.

Our research finds that loss of DLK1 impaired proliferation, survival, and engraftment of leukemia cells. Using a DLK1-directed antibody-drug conjugate (ADC) selectively eradicated ML-DS cells and achieved durable remissions in refractory PDX models.

While immunotherapies are transforming pediatric leukemia treatment, this work provides the first step as proof-of-concept that AML too can be targeted through unique, leukemia-specific vulnerabilities.

Find the publication at:

Verboon J L, et al. DLK1 is a GATA1s-Driven Dependency and Therapeutic Target in Down Syndrome-Associated Myeloid Leukemia. bioRxiv. 2025 Sep 13; doi: https://doi.org/10.1101/2024.08.30.608947