EnvIRONmental Aspects in Myelodysplastic Syndrome

Systemic iron overload is multifactorial in patients suffering from myelodysplastic syndrome (MDS). Disease-immanent ineffective erythropoiesis together with chronic red blood cell transfusion represent the main underlying reasons. However, like the genetic heterogeneity of MDS, iron homeostasis is also diverse in different MDS subtypes and can no longer be generalized. While a certain amount of iron and reactive oxygen species (ROS) are indispensable for proper hematological output, both are harmful if present in excess. Consequently, iron overload has been increasingly recognized as an important player in MDS, which is worth paying attention to. This review focuses on iron- and ROS-mediated effects in the bone marrow niche, their implications for hematopoiesis and their yet unclear involvement in clonal evolution. Moreover, we provide recent insights into hepcidin regulation in MDS and its interaction between erythropoiesis and inflammation. Based on Tet methylcytosine dioxygenase 2 (TET2), representing one of the most frequently mutated genes in MDS, leading to disturbances in both iron homeostasis and hematopoiesis, we highlight that different genetic alteration may have different implications and that a comprehensive workup is needed for a complete understanding and development of future therapies.

Download Full-text

Transient Elastography for the Detection of Hepatic Iron Overload in Patients with Myelodysplastic Syndrome

European Oncology & Haematology ◽

10.17925/eoh.2016.12.02.103 ◽

2016 ◽

Vol 12 (02) ◽

pp. 103

Author(s):

Malene Risum ◽

Toke Barfod ◽

Klas Raaschou-Jensen ◽

◽

...

Keyword(s):

Myelodysplastic Syndrome ◽

Iron Overload ◽

Transient Elastography ◽

Myeloproliferative Neoplasm ◽

Liver Stiffness ◽

Surrogate Marker ◽

Red Blood Cell Transfusion ◽

Hepatic Iron Overload ◽

Transfusion Dependency ◽

Myelomonocytic Leukemia

Background: In myelodysplastic syndrome (MDS), anemia often leads to red blood cell transfusion dependency and iron overload (IOL). Serum ferritin (SF) is used as a surrogate marker for IOL. IOL can lead to liver failure. Transient elastography (TE) also known as fibroscan is an easy and noninvasive procedure for liver stiffness measurements (LSM). Methods: Sixty patients with either MDS, chronic myelomonocytic leukemia with dysplastic features, acute myeloid leukemia progressed from MDS or myelodysplastic/ myeloproliferative neoplasm, unclassifiable were included. All patients underwent a fibroscan, had their SF measured and disease duration calculated. Patients were grouped according to transfusion dependency or independency status. Results: Transfusion dependent patients had significantly higher LSM than those who were transfusion independent (p=0.003). There was no positive correlation between SF and LSM (p=0.103) or time since diagnosis and LSM (p=0.886). Patients with elevated SF did not have significantly higher LSM compared to those with normal SF (p=0.583). Conclusion: These data indicate that transfusion dependency has an impact on liver stiffness in MDS. Longitudinel studies are needed to conclude whether TE is of value in monitoring IOL in MDS.

Download Full-text

A case of transfusion independence in a patient with myelodysplastic syndrome using deferasirox, sustained for two years after stopping therapy

Current Oncology ◽

10.3747/co.22.2100 ◽

2015 ◽

Vol 22 (2) ◽

pp. 128 ◽

Cited By ~ 4

Author(s):

D. Sanford ◽

C.C. Hsia

Keyword(s):

Myelodysplastic Syndrome ◽

Iron Overload ◽

Chelation Therapy ◽

Iron Chelation ◽

Iron Chelator ◽

Red Blood Cell Transfusion ◽

Transfusion Independence ◽

Clinical Complications ◽

Increased Risk ◽

History Of

Patients with myelodysplastic syndrome (mds) experience clinical complications related to progressive marrow failure and have an increased risk of developing acute myeloid leukemia. Frequent red blood cell transfusion can lead to clinical iron overload and is associated with decreased survival in mds patients. Iron chelation therapy reduces markers of iron overload and prevents end-organ damage.Here, we present the case of a patient with lowrisk mds with transfusional iron overload. He was treated for 2 years with an oral iron chelator, deferasirox, and after 12 months of treatment, he experienced a hemoglobin increase of more than 50 g/L, becoming transfusion-independent. He has remained transfusion-independent, with a normal hemoglobin level, for more than 2 years since stopping chelation therapy. Hematologic and erythroid responses have previously been reported in mds patients treated with iron chelation. The durability of our patient’sresponse suggests that iron chelation might alter the natural history of mds in some patients.

Download Full-text

The Interplay between Drivers of Erythropoiesis and Iron Homeostasis in Rare Hereditary Anemias: Tipping the Balance

International Journal of Molecular Sciences ◽

10.3390/ijms22042204 ◽

2021 ◽

Vol 22 (4) ◽

pp. 2204

Author(s):

Simon Grootendorst ◽

Jonathan de Wilde ◽

Birgit van Dooijeweert ◽

Annelies van Vuren ◽

Wouter van Solinge ◽

...

Keyword(s):

Iron Overload ◽

Iron Metabolism ◽

Iron Homeostasis ◽

Significant Problem ◽

Blood Transfusions ◽

Intrinsic Defects ◽

Chronic Anemia ◽

Erythroid Development ◽

Disease Specific

Rare hereditary anemias (RHA) represent a group of disorders characterized by either impaired production of erythrocytes or decreased survival (i.e., hemolysis). In RHA, the regulation of iron metabolism and erythropoiesis is often disturbed, leading to iron overload or worsening of chronic anemia due to unavailability of iron for erythropoiesis. Whereas iron overload generally is a well-recognized complication in patients requiring regular blood transfusions, it is also a significant problem in a large proportion of patients with RHA that are not transfusion dependent. This indicates that RHA share disease-specific defects in erythroid development that are linked to intrinsic defects in iron metabolism. In this review, we discuss the key regulators involved in the interplay between iron and erythropoiesis and their importance in the spectrum of RHA.

Download Full-text

Routes of Clonal Evolution into Complex Karyotypes in Myelodysplastic Syndrome Patients with 5q Deletion

International Journal of Molecular Sciences ◽

10.3390/ijms19103269 ◽

2018 ◽

Vol 19 (10) ◽

pp. 3269 ◽

Cited By ~ 1

Author(s):

Simone Feurstein ◽

Kathrin Thomay ◽

Winfried Hofmann ◽

Guntram Buesche ◽

Hans Kreipe ◽

...

Keyword(s):

Myelodysplastic Syndrome ◽

Myeloid Leukemia ◽

Clonal Evolution ◽

Suppressor Gene ◽

Trisomy 8 ◽

Multicolor Fish ◽

Catastrophic Event ◽

Evolution And Development ◽

Gene Tp53

Myelodysplastic syndrome (MDS) can easily transform into acute myeloid leukemia (AML), a process which is often associated with clonal evolution and development of complex karyotypes. Deletion of 5q (del(5q)) is the most frequent aberration in complex karyotypes. This prompted us to analyze clonal evolution in MDS patients with del(5q). There were 1684 patients with low and intermediate-risk MDS and del(5q) with or without one additional cytogenetic abnormality, who were investigated cytogenetically in our department, involving standard karyotyping, fluorescence in situ hybridization (FISH) and multicolor FISH. We identified 134 patients (8%) with aspects of clonal evolution. There are two main routes of cytogenetic clonal evolution: a stepwise accumulation of cytogenetic events over time and a catastrophic event, which we defined as the occurrence of two or more aberrations present at the same time, leading to a sudden development of highly complex clones. Of the 134 patients, 61% underwent a stepwise accumulation of events whereas 39% displayed a catastrophic event. Patients with isolated del(5q) showed significantly more often a stepwise accumulation of events rather than a catastrophic event. The most frequent aberrations in the group of stepwise accumulation were trisomy 8 and trisomy 21 which were significantly more frequent in this group compared to the catastrophic event group. In the group with catastrophic events, del(7q)/-7 and del(17p)/-17 were the most common aberrations. A loss of 17p, containing the tumor suppressor gene TP53, was found significantly more frequent in this group compared to the group of stepwise accumulation. This leads to the assumption that the loss of TP53 is the driving force in patients with del(5q) who undergo a sudden catastrophic event and evolve into complex karyotypes.

Download Full-text

Iron Homeostasis and Disorders in Dogs and Cats: A Review

Journal of the American Animal Hospital Association ◽

10.5326/jaaha-ms-5553 ◽

2011 ◽

Vol 47 (3) ◽

pp. 151-160 ◽

Cited By ~ 27

Author(s):

Jennifer L. McCown ◽

Andrew J. Specht

Keyword(s):

Iron Deficiency ◽

Iron Overload ◽

Iron Homeostasis ◽

Diagnostic Testing ◽

Clinical Manifestations ◽

Essential Element ◽

The Body ◽

Deficiency Anemia ◽

Enzyme Systems ◽

Living Organisms

Iron is an essential element for nearly all living organisms and disruption of iron homeostasis can lead to a number of clinical manifestations. Iron is used in the formation of both hemoglobin and myoglobin, as well as numerous enzyme systems of the body. Disorders of iron in the body include iron deficiency anemia, anemia of inflammatory disease, and iron overload. This article reviews normal iron metabolism, disease syndromes of iron imbalance, diagnostic testing, and treatment of either iron deficiency or excess. Recent advances in diagnosing iron deficiency using reticulocyte indices are reviewed.

Download Full-text

Targeted disruption of hepcidin in the liver recapitulates the hemochromatotic phenotype

Blood ◽

10.1182/blood-2014-01-550467 ◽

2014 ◽

Vol 123 (23) ◽

pp. 3646-3650 ◽

Cited By ~ 45

Author(s):

Sara Zumerle ◽

Jacques R. R. Mathieu ◽

Stéphanie Delga ◽

Mylène Heinis ◽

Lydie Viatte ◽

...

Keyword(s):

Iron Overload ◽

Iron Homeostasis ◽

Targeted Disruption ◽

Body Iron ◽

Key Points ◽

Main Regulator

Key Points Liver-specific hepcidin KO mice fully recapitulate the severe iron overload phenotype observed in the total KO mice. The hepcidin produced by hepatocytes is the main regulator of body iron homeostasis.

Download Full-text