Hematology, IRCCS Azienda Ospedaliera Universitaria San Martino – IST
Istituto Nazionale per la Ricerca sul Cancro, Genova. Italy.
2 Hematology and Bone Marrow Transplantation Unit, Ospedale Oncologico di Riferimento Regionale “Armando Businco”, Cagliari, Italy.
3 CRS4, Biomedicine Sector, Scientific and Technology Park of Sardinia, Pula, Cagliari, Italy;
4 Internal Medicine 2, University of Milano-Bicocca, Centre for Disorders of Iron Metabolism, ASST-Monza, S. Gerardo Hospital, Monza, Italy.
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recent decades we have been fortunate to witness the advent of new
technologies and of an expanded knowledge and application of chelation
therapies to the benefit of patients with iron overload. However,
extrapolation of learnings from thalassemia to the myelodysplastic
syndromes (MDS) has resulted in a fragmented and uncoordinated clinical
evidence base. We’re therefore forced to change our understanding of
MDS, looking with other eyes to observational studies that inform us
about the relationship between iron and tissue damage in these
subjects. The available evidence suggests that iron accumulation is
prognostically significant in MDS, but levels of accumulation
historically associated with organ damage (based on data generated in
the thalassemias) are infrequent. Emerging experimental data have
provided some insight into this paradox, as our understanding of
iron-induced tissue damage has evolved from a process of progressive
bulking of organs through high-volumes iron deposition, to one of
‘toxic’ damage inflicted through multiple cellular pathways. Damage
from iron may, therefore, occur prior to reaching reference thresholds,
and similarly, chelation may be of benefit before overt iron overload
is seen. In this review, we revisit the scientific and clinical
evidence for iron overload in MDS to better characterize the iron
overload phenotype in these patients, which differs from the classical
transfusional and non-transfusional iron overload syndrome. We hope
this will provide a conceptual framework to better understand the
complex associations between anemia, iron and clinical outcomes, to
accelerate progress in this area.
Iron Balance and Overload
|Figure 1. Schematic diagram illustrating iron homeostasis in pathologic conditions, and the sequence of events that leads to end organ damage in response to iron overload.|
Iron Overload in Myelodysplastic Syndromes
|Figure 2. Mechanistic illustration of disordered calcium handling (and in turn excitation-contraction coupling) and multiple ion channel disruption as a result of iron influx into the cardiac myocyte, with generation of dangerous reactive oxygen species.|
MDS and other Diseases
|Table 1. Different pattern of iron overload in different diseases.|
Therapeutic Potential in MDS Patients
Iron Chelation and Survival
AcknowledgementsEditorial assistance was provided by Kaivan Khavandi, MD.