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.
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 177, Monday Morning