Imaging flow cytometry documents incomplete resistance of human sickle F-cells to ex vivo hypoxia-induced sickling

摘要

We have read with great interest the "Perspectives" article by Steinberg et al in the January 23,2014, edition of Blood.1 The authors present a mathematical model that implies that the critical content of fetal hemoglobin (HbF) required to prevent polymerization of sickle hemoglobin is higher than the threshold HbF content that renders an erythrocyte detectable as an "F-cell" on immunofluorescent staining by flow cytometry. This would lead to a hypothesis that only a subset of F-cells are resistant to hypoxia-induced sickling. We obtained data from a new imaging flow cytometry assay that can qualitatively support this general principle, although with clear assay limitations that don't permit us to address quantitatively the predictions of Steinberg et al in detail. These new results show that intracellular HbF is a major factor influencing sickling, but it is clearly not the only factor.