Quantitative analysis of erythrocytes containing fetal hemoglobin (F cells) in children with sickle cell disease

Abstract

Variation in the level of fetal hemoglobin (HbF) accounts for much of the clinical heteroge-neity observed in patients with sickle cell disease (SCD). The HbF level has emerged as an important prognostic factor in both sickle cell pain and mortality, and a % HbF of 10-20% has been suggested as a threshold level for diminished clinical severity. The number of erythrocytes that contain HbF (termed F cells) may also be critically important, as F cells resist intravascular sickling and have preferential in vivo survival. Since F cells can be enumerated with high accuracy using flow cytometry methods, we prospectively studied a cohort of 242 children with SCD. Children with HbS and hereditary persistence of fetal hemoglobin (S/HPFH) had essentially 100% F cells. In contrast, children with homozygous sickle cell anemia (HbSS), HbS/ 0 thalassemia, or HbS/ thalassemia had significantly lower mean % F cell values (55.9, 61.6, and 51.3%, respectively; P 0.001), and children with HbSC had even fewer F cells (27.0%; P 0.001). There was a highly significant correlation between the % F cells and the log (% HbF), which was observed for the total population of children (r 0.95, P 0.001), as well as for each of the individual subgroups of children with HbSS (r 0.94, P 0.001), HbSC (r 0.89, P 0.001), or HbS/ 0 thalassemia and HbS/ thalassemia (r 0.95, P 0.001). This logarithmic correlation between % F cells and % HbF has not been previously described and has important implications for the pharmacologic manipulation of HbF in patients with SCD. Am.

PGC-1 Coactivator Activity Is Required for Murine Erythropoiesis

“…The human ␤-globin locus has been extensively studied as a paradigm for genetic regulation of lineage-and stage-specific gene expression (42), as well as for its clinical relevance to ␤-globin disorders. Elucidation of the molecular basis for ␥-globin gene silencing during definitive erythropoiesis in particular has been the focus of intense investigation, since coinheritance of genetic conditions that confer elevated ␥-globin synthesis alleviates many symptoms and at least some of the pathology associated with inherited ␤-globin disorders (43,44).…”

Nuclear Receptors TR2 and TR4 Recruit Multiple Epigenetic Transcriptional Corepressors That Associate Specifically with the Embryonic β-Type Globin Promoters in Differentiated Adult Erythroid Cells

“…The human ␤-globin locus is composed of ε-(embryonic), G␥-and A␥-(fetal), and ␦-and ␤-globin (adult) genes, which are spatially arranged from 5Ј to 3Ј and developmentally expressed in the same order (72). The elucidation of the molecular basis for ␥-globin silencing in the adult stage in particular has been the focus of intense investigation, since it has been observed that coinheritance of genetic conditions that confer elevated ␥-globin synthesis can significantly alleviate the symptoms of ␤-globin disorders (44,56). Previously, several adult-stage ␥-globin repressors have been identified, such as BCL11A and SOX6 that physically interact with each other to repress the ␥-globin genes (67,84,86), as well as Ikaros (42) and GATA1 (20).…”

A case of hereditary persistence of fetal haemoglobin

“…Thalassaemia syndromes comprise a large clinical spectrum and a well recognized observation is the inverse link between clinical severity and quantity of fetal haemoglobin (HbF) present 1 . It is now known that three types of globin that produce haemoglobin (Hb) change from e-globin (epsilone) to g-globin (gamma) in the fetus and to b-globin (beta) around birth.…”