In one of the largest studies to date, Voulgarelis et al (10) looked at 40 cases of SLE and similarly found frequent dysplastic changes, most notable in the erythroid
and megakaryocytic lineages, as well as ALIP that showed striking similarity to the control cases of MDS, refractory anemia subtype.
chaperone that facilitates folding of [alpha]-globin subunits for hemoglobin synthesis.
In infection, cytokines and their products therefore cause: (i) a diversion of iron into iron stores in the RES, resulting in decreased iron concentration in the plasma, thus limiting its availability to red cells for haemoglobin synthesis; (ii) an inhibition of erythroid
progenitor cell proliferation; and (iii) inappropriate production and activity of Epo.
Firstly, it is directly toxic to developing cells, causing an increased or high-normal MCV and vacuolation of erythroid
The ineffective hematopoiesis results in megaloblastoid changes of the erythroid
precursors in the bone marrow.
Bianchi N, Chiarabelli C, Borgatti M, Mischiati C, Fibach E, Gambari R (2001) Accumulation of gamma-globin mRNA and induction of erythroid
differentiation after treatment of human leukaemic K562 cells with tallimustine.
In a presentation titled, "From GWAS to the Clinic: Genome-Editing the Human Bcl11a Erythroid
Enhancer for Fetal Globin Elevation in the Hemoglobinopathies" (Abstract #53), new data were described demonstrating the effectiveness of knocking out the BCL11A Enhancer in hematopoietic stem and progenitor cells (HPSCs) as an approach to elevate fetal globin in a manner that is specific for red blood cell precursors (erythroid
-specific), thereby eliminating any effect of reduced BCL11A expression in HSPCs or other non-erythroid
lineage demonstrated left-shifted maturation with increased numbers of pronormoblasts and basophilic normoblasts, many of which contained multiple small cytoplasmic vacuoles.
Analysis of bone marrow aspirate showed cellular marrow with normal granulopoiesis and megakaryocytopoiesis, but the almost complete absence of erythroid
Hematopoietic tissue included megakaryocytes, maturing granulocytes, lymphocytes and erythroid
NF-E2 is expressed only in erythroid
cells, megakaryocytes, and mast cells.
The major issue is that the bone marrow erythroid
mass fails to expand appropriately in response to anaemia.