The Use of Pro-Apoptotic Marker, FoxO3 To Distinguish Erythroid Dominant Malignancies.
Rajan Dewar, Roya Khosravi-Far. Beth Israel Deaconess Medical Center & Harvard Medical School, Boston, MA; Harvard Medical School, Boston, MA
Background: Differentiation of Erythroid dominant myelodysplastic syndrome (E-MDS) and Erythroleukemia (FAB-M6), based on cell/blast counting is frequently difficult. We attempted to apply biological difference to distinguish E-MDS and M6 employing the marker FoxO3. FoxO3 is a known pro-apoptotic protein existing in a cytoplasmic-inactivated form, transported to the nucleus in an activated form. In this study, we compare FoxO3, Ki-67 (proliferation), CAIX, HIF-1α (hypoxic markers) among the erythroid population (Glycophorin A and E-cadherin) in MDS-E, M6 and benign marrows with reactive erythroid hyperplasia.
Design: We studied 11 archival bone marrow samples with MDS-E (M:E<1; n=4), Acute erythroleukemia (n=4) and benign erythroid hyperplasia marrow (M:E<1; n=3). The following markers were employed: FoxO3 (Millipore), Ki-67 (Novocastra); Carbonic Anhydrase IX (CAIX-Novus Biologics); Hypoxia Inducible Factor-1α (HIF-1; Novus); E-cadherin (Novocastra) and Glycophorin A. Gly A and E-Cadherin were used to identify erythroid populations. The expression of HIF-1, CAIX, FoxO3 and Ki-67 were estimated within these populations.
Results: Erythroid precursors in M6 show increased cytoplasmic but no nuclear FoxO3 expression (n=3/4).
MDS-E samples, on the other hand showed increased nuclear and cytoplasmic FoxO3 expression (n=4/4).
Both differ from the benign group with respect to proliferation. CAIX and HIF-1 expression were not significantly different among the 3 groups.
Conclusions: Leukemogenesis is a step wise process involving multiple genetic defects. Here, our initial observations is that in erythroleukemia (M6), defective FoxO3 localization to nucleus correlates with leukemogenesis. Further, a multiplex marker approach may be useful in distinguishing diagnostically challenging cases of benign erythroid hyperplasias & E-MDS from M6.
Monday, February 28, 2011 1:00 PM
Poster Session II # 188, Monday Afternoon