[1183] FOXP2 Deletion May Represent a Candidate Biomarker for Myelodysplastic Syndromes

CV Curry, I Nandi, WT Huang, FA Monzon, L Novoa-Takara, CC Chang. The Methodist Hospital, Houston, TX; Rice University, Houston, TX; Chang Gung University College of Medicine, Kaohsiung, Taiwan; Weill Medical College of Cornell University, New York, NY; Medical College of Wisconsin, Milwaukee, WI

Background: The pathogenesis of Myelodysplastic Syndromes (MDS) is poorly understood and no reliable biomarkers are available. Our previous study using high resolution 250K single-nucleotide polymorphism (SNP) array in 12 flow cytometry (FCM) sorted MDS bone marrow samples identified 2 cases with deletion of the FOXP2 gene located at 7q31.1 (cytogenetically cryptic deletion of 7q31.1 in only erythroid fraction and whole chromosome 7 deletion in both erythroid and blastic fractions, respectively). Deletion of FOXP2 was confirmed by real-time quantitative PCR (RQ-PCR). Since 7q31.1 is frequently deleted in MDSs, cryptic deletion of FOXP2, particularly in the erythroid fraction, may represent a potential biomarker for MDS patients without cytogenetic abnormalities.
Design: Twenty-six cryopreserved bone marrow samples consist of 8 controls and 18 MDS cases (8 low-grade, 10 high-grade), including 8 cases from the previous SNP study. The samples were fractionated into erythroid (CD71 bright/CD34-) and lymphoid fractions (CD45 bright/low side-scatter) using multicolor FCM. FOXP2 deletion status was analyzed by performing RQ-PCR from erythroid and lymphoid fractions. In each case, FOXP2 to -actin ratio of erythroid fraction was normalized to the same ratio of lymphoid fractions. The FOXP2 gene deletion was correlated with cytogenetics and SNP analysis results.
Results: None of the control cases showed FOXP2 deletion. Four out of 18 (22%) MDS samples demonstrated FOXP2 deletion; three were low-grade (2 refractory anemia, 1 5q- syndrome) and one was high-grade (therapy-related). All three low-grade MDSs showed normal karyotype for chromosome 7 (2 cases with normal karyotype, 1 with 5q-). The high-grade MDS had complex cytogenetic abnormalities including monosomy 7. The RQ-PCR results were consistent with SNP array data in all cases studied by SNP array previously.
Conclusions: Our studies suggested that deletion of the FOXP2 gene, a member of the FOX transcriptional factor family, may be an early event in MDS and may represent a candidate biomarker. Further studies are needed to confirm our observation and to characterize the function of FOXP2 in hematopoiesis for its role in the pathogenesis of MDS.
Category: Hematopathology

Monday, March 9, 2009 9:30 AM

Poster Session I Stowell-Orbison/Autopsy Award # 177, Monday Morning