Blood: Heterogeneous mechanism of hemoglobin-induced expression in sickle cell disease and beta-thalassemia fetal hemoglobin

Reversing the switching development of hemoglobin from fetal hemoglobin (HbF, alpha2 x 2) to adult (HbA, alpha2 beta 2) is an important treatment for sickle cell disease (SCD) and beta-thalassemiaIn healthy people, SCD patients, and patients treated with the drug HbF induction, HbF is present only in a red blood cell subgroup called F-celldespite more than 50 years of observation, the reason for this HbF isocellular expression pattern is unclear, even in cells with the same genesadult F cells may represent a reversal of the genetic and transcription altimetry state from an established cell to an embryonic-like epigenetic, or that the isolated and post-transcription events of the gamma-globin gene may be the basis for the ishesive cell expression patternIn this study, researchers learned about hbF activation by developing techniques that isolated late-stage red blood cell F cells and non-F cells (A-cells) that matched the differentiation phase from human HUDEP2 class red blood cell lines and protozoa red blood cell culturetranscription and proteomic analysis of these cells showed that the differences between F-cells and A cells in RNA levels were very small, both under baseline conditions and after treatment with HbF-induced hydroxylurea or pomadoaminessurprising, the researchers did not find any known HbF regulators, including BCL11A or LRF, that differ in expression, which may explain The activation of HbFthis study showed no significant difference between F-adult red blood cells and cells that did not express HbF, and the main differences may occur at the transcription levels at the b-pearl protein site