the second step of heme biosynthesis (Liu et al., Nat Comm 2020), and ferrochelatase (FECH),
the last enzyme of the heme biosynthetic pathway; ii) activating the RNA binding activity of
Iron Regulatory Protein 1 (IRP1) that blocks the translation of ALAS2, an erythroid specific
enzyme that catalyzes the first step of heme biosynthesis.
Not only low, but also high iron and heme levels are detrimental to erythroid cells. Free heme,
unbound to proteins, can intercalate into lipid membranes enhancing membrane
permeability; this is an abundant source of redox-active iron that can increase toxic free
hydroxyl radicals through the Fenton reaction, thus promoting cell lysis and death
(Chiabrando et al., 2014). For this reason cells have developed mechanisms that function as
safety valves in case of excessive iron or heme. The iron exporter ferroportin is highly
expressed on the plasma membrane of erythroblasts and erythrocytes and can release the
metal into the blood stream to avoid oxidative injury and hemolytic anemia due to excess iron
concentration (Zhang et al., 2018). The feline leukemia virus type C receptor (FLVCR) may
export heme in conditions of excess (Chiabrando et al., 2014).
Iron regulates the erythropoietic activity not only directly, as described above, but also
indirectly. In iron deficiency, EPO production in the kidney is attenuated by the reduced HIF-
2�� translation due to the binding of IRP1 to HIF-2�� 5’UTR IRE (Ghosh et al., Cell Met 2015),
that would translate into a suppression of erythropoiesis. However, this is avoided by TFR2, a
partner of the EPO receptor that has been shown to modulate the EPO sensitivity of erythroid
precursors (Nai et al., 2015). Decreased 2Fe-TF reduces TFR2 on the surface of erythroid
precursors (Pagani et al., 2015), thus maintaining the EPO-EPOR activation irrespective of
decreased EPO. The simultaneous reduction of TFR2 on the plasma membrane of hepatocytes
reduces hepcidin levels, favoring iron entry into the blood stream to support the erythroid
needs.
Recent findings suggest that iron plays an essential role not only in terminal erythropoiesis,
but also in the maintenance of hematopoietic stem cell function (Muto et al., 2017), and in
the choice between megakaryocyte or erythroid commitment, favoring the former in iron
deficiency (Xavier-Ferrucio et al., 2019). Further studies are needed to fully clarify the
molecular mechanisms involved in the regulation of these processes.
SCIENTIFIC PROGRAMME
SESSION I
BONE MARROW
RESPONSE TO VIRAL
INFECTIONS
SESSION II
HAEMATOLOGICAL
RESPONSE TO SARS
COV2 INFECTION
SESSION III
DYSERYTHROPOIESIS IN
CLONAL HAEMOPOIESIS
AND MDS
SESSION IV
ERYTHROPOIESIS
CONTROL
SESSION V
ERYTHROPOIESIS
CONTROL : PHASE 2
SESSION VI
IRON METABOLISM
AND ERYTHROPOIESIS
SESSION VII
INHERITED
DYSERYTHROPOIESIS
SESSION VIII
GENE THERAPY/EDITION
SESSION IX – DRUGS
AND INEFFECTIVE
ERYTHROPOIESIS
SELECTED ABSTRACTS
FOR AN ORAL
PRESENTATION
SELECTED ABSTRACTS
FOR A POSTER
PRESENTATION
FACULTY DISCLOSURES