Joseph Oved, MD | Aplastic Anemia & MDS International Foundation

Joseph Oved, MD

Determinants of immune escape versus malignant clonal evolution in pediatric acquired aplastic anemia
Original Research Center: 
The Children’s Hospital of Philadelphia
Pubmed Author Name: 
Oved J

Aplastic Anemia is a disease that results in the destruction of hematopoietic stem cells in the bone marrow by the immune system. Although the exact mechanism of this pathology is not fully understood, the prevailing model proposes that the immune system and specifically T cells are responsible for this destruction. Pediatric and adult aplastic anemia, while clinically similar in their presentation may in fact be representative of different subsets of a spectrum of aplastic anemia. Our group and others have shown that adult patients with aplastic anemia have a tendency to develop cell populations that are predisposed to myelodysplastic syndrome and leukemia. In the pediatric population however, we found that patients tend to develop cell populations that have mutations in certain genes (i.e. PIGA and HLA) which we believe are necessary for the immune system to recognize and kill the stem cells. In this way pediatric patients have a mechanism through which they can evade destruction by the immune system, and regenerate their stem cell population. We propose extending these studies in a bigger pediatric patient cohort to show which specific genetic mutations are protective to the patient. We also want to further our studies to show that pediatric patients that develop these immune escape variants, do not have an increased probability of progressing to myelodysplastic syndrome or leukemia. Furthermore, we aim to show that in patients with both immune escape variants and myelodysplastic changes, these mutations occurred independently of one another. These data can help determine which pediatric patients are most suitable for treatment with immune suppressive therapy versus bone marrow transplantation. They will also open new avenues for development of precision based targeted therapeutics in the future.