Cellular normoxic biophysical markers of hydroxyurea treatment in sickle cell disease

Poorya Hosseini, Sabia Z. Abidi, E. Du, Dimitrios P. Papageorgiou, Youngwoon Choi, Yongkeun Park, John M. Higgins, Gregory J. Kato, Subra Suresh, Ming Dao, Zahid Yaqoob, Peter T C So

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)9527-9532
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number34
DOIs
StatePublished - Aug 23 2016
Externally publishedYes

Fingerprint

Hydroxyurea
Sickle Cell Anemia
Fetal Hemoglobin
Blood Transfusion
Therapeutics
Cell Count
Erythrocytes
Pharmaceutical Preparations

Keywords

  • Biomarkers
  • Cell deformability
  • Cell volume
  • Cellular properties
  • Sickle cell anemia

ASJC Scopus subject areas

  • General

Cite this

Cellular normoxic biophysical markers of hydroxyurea treatment in sickle cell disease. / Hosseini, Poorya; Abidi, Sabia Z.; Du, E.; Papageorgiou, Dimitrios P.; Choi, Youngwoon; Park, Yongkeun; Higgins, John M.; Kato, Gregory J.; Suresh, Subra; Dao, Ming; Yaqoob, Zahid; So, Peter T C.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 113, No. 34, 23.08.2016, p. 9527-9532.

Research output: Contribution to journalArticle

Hosseini, P, Abidi, SZ, Du, E, Papageorgiou, DP, Choi, Y, Park, Y, Higgins, JM, Kato, GJ, Suresh, S, Dao, M, Yaqoob, Z & So, PTC 2016, 'Cellular normoxic biophysical markers of hydroxyurea treatment in sickle cell disease', Proceedings of the National Academy of Sciences of the United States of America, vol. 113, no. 34, pp. 9527-9532. https://doi.org/10.1073/pnas.1610435113
Hosseini, Poorya ; Abidi, Sabia Z. ; Du, E. ; Papageorgiou, Dimitrios P. ; Choi, Youngwoon ; Park, Yongkeun ; Higgins, John M. ; Kato, Gregory J. ; Suresh, Subra ; Dao, Ming ; Yaqoob, Zahid ; So, Peter T C. / Cellular normoxic biophysical markers of hydroxyurea treatment in sickle cell disease. In: Proceedings of the National Academy of Sciences of the United States of America. 2016 ; Vol. 113, No. 34. pp. 9527-9532.
@article{d70d30311152436baf10fc1549615631,
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.",
keywords = "Biomarkers, Cell deformability, Cell volume, Cellular properties, Sickle cell anemia",
author = "Poorya Hosseini and Abidi, {Sabia Z.} and E. Du and Papageorgiou, {Dimitrios P.} and Youngwoon Choi and Yongkeun Park and Higgins, {John M.} and Kato, {Gregory J.} and Subra Suresh and Ming Dao and Zahid Yaqoob and So, {Peter T C}",
year = "2016",
month = "8",
day = "23",
doi = "10.1073/pnas.1610435113",
language = "English (US)",
volume = "113",
pages = "9527--9532",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "34",

}

TY - JOUR

T1 - Cellular normoxic biophysical markers of hydroxyurea treatment in sickle cell disease

AU - Hosseini, Poorya

AU - Abidi, Sabia Z.

AU - Du, E.

AU - Papageorgiou, Dimitrios P.

AU - Choi, Youngwoon

AU - Park, Yongkeun

AU - Higgins, John M.

AU - Kato, Gregory J.

AU - Suresh, Subra

AU - Dao, Ming

AU - Yaqoob, Zahid

AU - So, Peter T C

PY - 2016/8/23

Y1 - 2016/8/23

N2 - 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.

AB - 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.

KW - Biomarkers

KW - Cell deformability

KW - Cell volume

KW - Cellular properties

KW - Sickle cell anemia

UR - http://www.scopus.com/inward/record.url?scp=84983372868&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84983372868&partnerID=8YFLogxK

U2 - 10.1073/pnas.1610435113

DO - 10.1073/pnas.1610435113

M3 - Article

VL - 113

SP - 9527

EP - 9532

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 34

ER -