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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)




  • F Lin
  • B Saleh
  • D.L. Hodge
  • K Boelte
  • T Chan
  • M Karwan
  • J.P. Keller
  • H.A. Young


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.

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