Bone Marrow Failure Research

The Comprehensive Bone Marrow Failure Center (CBMFC) at Children’s Hospital of Philadelphia (CHOP) is dedicated to research that improves diagnosis and therapy for bone marrow failure (BMF) patients. We bridge the gap from bench to bedside with strong synergy between patient care and ongoing basic, translational and clinical research. As leaders in the field of bone marrow failure research, our long-term efforts and resources are committed to improving the health and well-being of our patients and their families.

Current Research Studies

Biological basis of bone marrow failure

Many patients with bone marrow failure come to the CBMFC having already experienced significant bone marrow stem cell losses. This preclinical study, funded by a RO1 grant from the National Heart, Lung and Blood Institute, seeks to determine the starting point of inherited BMF. Knowing when and where BMF begins can help inform possible treatments. Many current treatments for BMF are inspired by the idea that the condition begins during childhood in the bone marrow itself. However, in the case of Fanconi anemia (FA) — the most common type of inherited bone marrow failure — new research shows that the disease begins in utero, before the bone marrow itself even exists. However, until the first year of life, these stem cells may still be amenable to treatments not currently considered in the context of the bone marrow environment. By understanding the biologic basis of Fanconi anemia, we hope to discover new opportunities to ameliorate — or even cure — the damage caused by this disease soon after birth.

Immune system’s role in the loss of hemopoietic stem cells in BMF

Through a collaboration with the University of Pennsylvania (Penn), this study seeks to better understand the immune system’s role in acquired aplastic anemia, a type of BMF in which a patient’s immune system targets the body’s stem cells. One current treatment for acquired aplastic anemia is bone marrow transplant. However, understanding which aspect of the stem cell the immune system is targeting may allow for specific treatments that would involve less manipulation of a patient’s immune system. 

Gene therapy for Fanconi anemia

Funded through CHOP’s Cell and Gene Therapy Initiative, which seeks to further expand the hospital’s longstanding position at the forefront of cell and gene therapy research, this two-year study will develop a new approach to stem cell treatment for BMF. In the case of FA, stem cells are extremely fragile and often cannot withstand the process of mobilization from the bone marrow, genetic modification and reinfusion to the patient’s body. Currently studied in mouse models, this approach seeks to deliver healthy stem cells directly to the bone marrow using a viral vector, thereby avoiding the entire process of cell manipulation that currently occurs outside of the body. Read more about viral vector gene therapy for BMF.

Aplastic anemia and the outgrowth of myelodysplasia

Leukemia — or its precursor, myelodysplasia — is one devastating risk of BMF. This research study aims to understand the hallmarks of when aplastic anemia, or loss of blood function, develops into leukemia. Through a partnership with CHOP’s Cancer Predisposition Program, we are working to understand the genetic drivers of this evolution to myelodysplasia. Once these specific genetic mutations have been identified, we can begin to understand how this evolution happens and take steps to prevent it.

Educational Opportunities

The CBMFC offers many training opportunities for interns. Our interns typically work on translational research projects. Contact us to learn more about the educational opportunities available in our program.

Publications

Our physician scientists have produced and published extensively across the field. View our published papers.

Clinical Studies

An important resource for our research is the CHOP/Penn Bone Marrow Failure Data Registry and Sample Repository, which provides a critical opportunity to test findings from animal studies on human tissue. Since its inception, our Repository has grown to include over 650 unique patients/families and over 10,000 samples. All of our patients have the opportunity to participate in research discoveries that drive the next generation of cures for patients with BMF disorders. Contact us for more information.


Next Steps