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SPORE Projects

Our SPORE in Leukemia includes the following four translational projects:

Project 1:  Molecular determinants of decitabine responsiveness.  
  •  Basic Science Co-Leader: Timothy Ley, MD
  • Clinical Science Co-Leader: John Welch, MD, PhD

A prospective clinical trial is being performed to test the hypotheses that specific gene mutations and/or gene expression patterns in AML will predict response to decitabine therapy and that next generation sequencing will provide a sensitive and quantitative method to assess clonal responses to decitabine. 

 Project 2: Targeting the bone marrow microenvironment in acute lymphocytic leukemia. 

  •  Basic Science Co-Leader: Daniel Link, MD
  •  Clinical Science Co-Leader: Geoffrey Uy, MD

This project builds on basic research showing that treatment with G-CSF induces marked changes in the bone marrow microenvironment that suppress lymphopoiesis. A prospective clinical trial will test the hypothesis that upfront treatment with G-CSF and a CXCR4 antagonist will sensitize acute lymphocytic leukemia cells to chemotherapy by interfering with trophic interactions between marrow stroma and leukemic blasts.

 Project 3: Development of RNA splicing modulators for myelodysplastic syndromes and AML.

  •   Basic Science Co-Leader: Timothy Graubert, MD
  •  Clinical Science Co-Leader: Matthew Walter, MD

We and others identified highly recurring mutations in genes involved in RNA splicing in MDS and AML. This project will test the novel hypothesis that agents that target RNA splicing may be selectively toxic to AML or MDS cell harboring such mutations

Project 4: Epigenetic modulation of graft versus host disease and graft versus leukemia.   

  •  Basic Science Co-Leader: John F. DiPersio, MD, PhD
  •  Clinical Science Co-Leader: Peter Westevelt, MD, PhD

This project builds on a novel observation that treatment with hypomethylating agents induces functional regulatory T cell responses. A prospective clinical trial is being performed to test the hypothesis that treatment with 5-azacitidine will attenuate graft versus host disease while preserving graft versus leukemia in patients with leukemia undergoing allogeneic stem cell transplantation.