Leukemia Models

Ribosomal proteins (Rps) are essential for functional ribosomes, protein synthesis, and proliferative cell growth. Paradoxically, mutation of Rps can actually promote growth and proliferation and, in some cases, bestow predisposition to cancer. Our work provided the first rationale to explain the counter-intuitive organ overgrowth phenotypes observed for Drosophila Rp mutants by revealing that Rp mutants can drive tissue overgrowth cell extrinsically, whereby reduced Rps in the hormone-secreting gland of the larvae decreases activity of the steroid hormone ecdysone, extending the growth phase of development and causing tissue overgrowth. This project aims to extend these studies to better understand how Rp mutations cause the hypoplastic anemia associated with the human leukemia. Thus we have developed Drosophila models to specifically reduce Rps in the hematopoietic system to gain novel insights into how Rp mutations can promote leukemia in humans. This project will provide much needed insight into the processes linking reduced levels of Rps to cancer predisposition.