Modeling Marrow Failure and MDS for Novel Therapeutics
Abstract
One of the potentially life-threatening complications of inherited or acquired bone marrow failure is progression to myelodysplastic syndrome (MDS). MDS is prone to develop into leukemia. Treatment options are limited for MDS in patients with marrow failure. The acquisition of monosomy 7 (the loss of one copy of chromosome 7) or del7q (the loss of part of chromosome 7) in MDS is an ominous development associated with a high risk of progression to leukemia and poor survival. Treatment options are limited for MDS arising from marrow failure. Currently the only curative treatment is a bone marrow transplant, but successful treatment is limited by donor availability, treatment-related toxicities, long-term effects of treatment, and graft-versus-host disease (where the donated marrow launches an immune attack against the patient s body). The lack of experimental model systems to study monosomy 7/del7q poses a major barrier impeding the development of new treatments. Induced pluripotent stem cells (iPSC) derived from patient bone marrow cells offer an attractive model system for MDS. iPSC can grow indefinitely in culture and can mature into blood cells. In collaboration with Dr. Eirini Papapetrou, we developed a novel del7q MDS model utilizing iPSC from patients with an inherited bone marrow failure syndrome called Shwachman Diamond syndrome. Patients with Shwachman-Diamond syndrome develop bone marrow failure and are at high risk for developing MDS, which is frequently characterized by chromosome 7 loss. We will utilize this novel del7q/marrow failure MDS model to identify genes and molecular pathways that are important for the growth and survival of the del7q cells but not for the non-del7q cells. The goal of this study is to identify targets for new medical therapies to treat or prevent monosomy 7/del7q MDS arising in the context of marrow failure. This novel del7q/SDS iPSC model system can also be used to study how MDS develops and to identify potential biomarkers for patients at high risk for developing MDS.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1610054
Entities
People
- Akiko Shimamura
Organizations
- Harvard University
- United States Army