Mitochondrial ferritin expression in erythroid cells from patients with sideroblastic anemia

The sideroblastic anemias are characterized
by ring sideroblasts, that is, red cell precursors
with mitochondrial iron accumulation.
We therefore studied the expression of mitochondrial
ferritin (MtF) in these conditions.
Erythroid cells from 13 patients with refractory
anemia with ring sideroblasts (RARS)
and 3 patients with X-linked sideroblastic
anemia (XLSA) were analyzed for the distribution
of cytoplasmicHferritin (HF) and MtF
using immunocytochemical methods. We
also studied 11 healthy controls, 5 patients
with refractory anemia without ring sideroblasts
(RA), and 7 patients with RA with
excess of blasts (RAEB). About one fourth
of normal immature red cells, mostly proerythroblasts
and basophilic erythroblasts,
showed diffuse cytoplasmic positivity for
HF, but very few were positive for MtF (0%-
10%). Similar patterns were found in anemic
patients without ring sideroblasts. In contrast,
many erythroblasts from patients with
sideroblastic anemia (82%-90% in XLSAand
36%-84% in RARS) were positive for MtF,
which regularly appeared as granules ringing
the nucleus. Double immunocytochemical
staining confirmed the different cellular
distribution of HF and MtF. There was a
highly significant relationship between the
percentage of MtF erythroblasts and that
of ring sideroblasts (Spearman R 0.90;
P < .0001). Reverse transcription-polymerase
chain reaction studies demonstrated
the presence of MtF mRNA in circulating
reticulocytes of 2 patients with XLSAbut not
in controls. These findings suggest that
most of the iron deposited in perinuclear
mitochondria of ring sideroblasts is present
in the form of MtF and that this latter might
be a specific marker of sideroblastic anemia.