title: Cellular normoxic biophysical markers of hydroxyurea treatment in sickle cell disease.
abstract: Hydroxyurea (HU) has been used clinically to reduce the frequency of painful crisis and the need for blood transfusion in sickle cell disease (SCD) patients. However, the mechanisms underlying such beneficial effects of HU treatment are still not fully understood. Studies have indicated a weak correlation between clinical outcome and molecular markers, and the scientific quest to develop companion biophysical markers have mostly targeted studies of blood properties under hypoxia. Using a common-path interferometric technique, we measure biomechanical and morphological properties of individual red blood cells in SCD patients as a function of cell density, and investigate the correlation of these biophysical properties with drug intake as well as other clinically measured parameters. Our results show that patient-specific HU effects on the cellular biophysical properties are detectable at normoxia, and that these properties are strongly correlated with the clinically measured mean cellular volume rather than fetal hemoglobin level.
authors: Laser Biomedical Research Center, Massachusetts Institute of Technology, Cambridge, MA 02139; Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139;
authors: Poorya
authors: P
authors: Hosseini
authors: Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139;
authors: Sabia Z
authors: SZ
authors: Abidi
authors: Department of Ocean and Mechanical Engineering, Florida Atlantic University, Boca Raton, FL 33431;
authors: E
authors: E
authors: Du
authors: Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139;
authors: Dimitrios P
authors: DP
authors: Papageorgiou
authors: School of Biomedical Engineering, Korea University, Seoul 136-701, Korea;
authors: Youngwoon
authors: Y
authors: Choi
authors: Department of Physics, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea;
authors: YongKeun
authors: Y
authors: Park
authors: Department of Systems Biology, Harvard Medical School, Boston, MA 02115;
authors: John M
authors: JM
authors: Higgins
authors: Department of Medicine, Division of Hematology-Oncology, University of Pittsburgh, Pittsburgh, PA 15261;
authors: Gregory J
authors: GJ
authors: Kato
authors: Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213; Department of Materials Science and Engineering, Carnegie Mellon University, Pittsburgh, PA 15213; Department of Computational Biology, Carnegie Mellon University, Pittsburgh, PA 15213 mingdao@mit.edu zyaqoob@mit.edu suresh@cmu.edu.
authors: Subra
authors: S
authors: Suresh
authors: Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139; mingdao@mit.edu zyaqoob@mit.edu suresh@cmu.edu.
authors: Ming
authors: M
authors: Dao
authors: Laser Biomedical Research Center, Massachusetts Institute of Technology, Cambridge, MA 02139; mingdao@mit.edu zyaqoob@mit.edu suresh@cmu.edu.
authors: Zahid
authors: Z
authors: Yaqoob
authors: Laser Biomedical Research Center, Massachusetts Institute of Technology, Cambridge, MA 02139; Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139;
authors: Peter T C
authors: PT
authors: So
mesh_terms: D000755:Anemia, Sickle Cell / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D000986:Antisickling Agents / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood; D001772:Blood Cell Count; D001803:Blood Transfusion; D004907:Erythrocyte Deformability; D004912:Erythrocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005319:Fetal Hemoglobin; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology*; D008857:Microscopy, Interference; D010100:Oxygen / Q000494:pharmacology
chemical_list: D000986:Antisickling Agents; D015415:Biomarkers; D005319:Fetal Hemoglobin; D010100:Oxygen; D006918:Hydroxyurea
keywords: biomarkers; cell deformability; cell volume; cellular properties; sickle cell anemia