October 9 - 12, 2012
Building 10 & Natcher Conference Center
- General Schedule of Events
- Opening Plenary Session
- Concurrent Symposia Sessions
- Poster Sessions
- National Graduate Student Research Conference
- FARE Award Ceremony
- Special Exhibits on Resources for Intramural Research
- TSA Research Festival Exhibit Show
- Clinical Center Tours
- Research Festival Committees
- Past Research Festivals
IFN-gamma causes aplastic anemia by altering HSC composition and interrupting lineage differentiation
| Friday, November 08, 2013 — Poster Session III | |||
|---|---|---|---|
10:00 a.m. – 12:00 p.m. |
FAES Academic Center (Upper-Level Terrace) |
NCI |
STEMCELL-7 |
Authors
- F Lin
- B Saleh
- D.L. Hodge
- K Boelte
- T Chan
- M Karwan
- J.P. Keller
- H.A. Young
Abstract
Aplastic anemia (AA) is characterized by hypocellular marrow and pancytopenia with largely unknown etiology. Since IFN-γ and T-bet can be detected in peripheral blood of AA patients, it was believed autoreactive T lymphocytes were invovled in destroying the hematopoietic stem cells (HSCs) in the bone marrow (BM). We have observed AA-like symptoms in our IFN-γ AU-rich element (ARE) - deleted (del) mice which constitutively express low level of IFN-γ under physiological condition. In these mice, we did not observe infiltration of T cells in BM, and these T cells appeared to be non-pathogenic. When studying HSC and progenitor composition, we observed dramatic decreases in common myeloid progenitors (CMP), megakaryocyte/erythrocyte progenitors (MEP) and granulocyte/monocyte progenitors (GMP).We also saw a disruption in erythropoiesis and B cell differentiation. The same phenomena were also observed in WT recipients of ARE-del BM. In conclusion, our data suggests that AA occurs when IFN-γ inhibits the generation of CMP from multipotent progenitors and prevents lineage differentiation, as opposed to infiltration of autoreactive T cells into the BM. The finding provides a possible pathogenesis of AA in certain patient populations and would be useful in improving treatment as well as maintaining a disease free status.
