Decreased Expression of Myelopoiesis Determining Factor PU.1 in Myelodysplastic Syndrome (MDS)
Daniel G Leino, David P Arps, Jason X Cheng. University of Michigan, Ann Arbor, MI
Background: Normal myelopoiesis is controlled by several key transcription factors including PU.1. Expression level of PU.1 determines myeloid lineages. Previous studies in mice have shown aberrant PU.1 expression can result in the abnormal myelopoiesis, which is typically seen in MDS. The importance of PU.1 in myelopoiesis has been well documented; however the pathogenetic role of PU.1 in MDS remains unknown.
Design: In this pilot study, 14 clinical cases with myelodysplasia, including various subtypes of MDS and chronic myelomonocytic leukemia (CMML) were stratified according to WHO 2008 diagnostic criteria. Immunohistochemical studies for PU.1 were performed on the bone marrow trephine core biopsies and normal controls. Three independent reviewers assessed PU.1 expression. The degree of myelodysplasia was evaluated independently on the bone marrow aspirate.
Results: Normal bone marrow shows highest expression of PU.1 in mature monocytes and granulocytes. Low-level PU.1 expression is seen in myeloid progenitors, while erythroid and megakaryocytes are negative. A majority of cases with normal karyotype show decreased expression of PU.1 in mature granulocytes. In contrast, cases with abnormal cytogenetics, especially deletion 7q and deletion 5q do not show significant reduction in PU.1 expression. Our cases suggest that chemotherapy affects PU.1 expression in MDS. None of the CMML cases showed loss of PU.1 expression.
Conclusions: Aberrant PU.1 expression can be seen in subtypes of MDS. Our study shows alteration of PU.1 expression correlates to cytogenetic categories in MDS. PU.1 expression may be a useful biomarker to assist in the diagnosis of MDS, and monitoring response to therapy.
Tuesday, March 20, 2012 9:30 AM
Poster Session III # 236, Tuesday Morning