Myelodysplastic syndrome pathophysiology: Difference between revisions

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Revision as of 18:49, 8 December 2015

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Nawal Muazam M.D.[2]

Overview

Pathophysiology

Pathogenesis

Genetics

Associated conditions

Myelodysplastic syndrome may be associated with:^[1]

Fanconi syndrome
Diamond-blackfan syndrome
Shwachman-diamond syndrome

Gross Pathology

On gross pathology, a well , subcapsular tumor may be suggestive of myelodysplastic syndrome.^[1]

Microscopic Pathology

On microscopic histopathological analysis, dyserythropoiesis, dysgranulopoiesis, and dysmegakaryocytopoiesis are findings of myelodysplastic syndrome.^[1]

Gallery

Immunohistochemistry

References

↑ ^1.0 ^1.1 ^1.2 Associations of myelodysplastic syndromes. Librepathology (2015). http://librepathology.org/wiki/index.php/Myelodysplastic_syndromes. Accessed on December 8, 2015

Template:WikiDoc Sources

[Librepathology-1] 1.0 ^1.1 ^1.2 Associations of myelodysplastic syndromes. Librepathology (2015). http://librepathology.org/wiki/index.php/Myelodysplastic_syndromes. Accessed on December 8, 2015

[1]

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 ==Overview==
 ==Pathophysiology==
-MDS is thought to arise from [[mutation]]s in the [[hematopoietic stem cell|multi-potent bone marrow stem cell]], but the specific defects responsible for these diseases remain poorly understood.  [[Cellular differentiation|Differentiation]] of blood precursor cells is impaired, and there is a significant increase in levels of cell death [[apoptosis]] in bone marrow cells. Clonal expansion of the abnormal cells results in the production of cells which have lost the ability to differentiate. If the overall percentage of bone marrow [[Myeloblasts|blasts]] rises over a particular cutoff (20% for [[Myelodysplastic syndrome#WHO classification|WHO]] and 30% for [[Myelodysplastic syndrome#French-American-British (FAB) classification|FAB]]) then transformation to [[acute myeloid leukemia|leukemia]] (specifically [[acute myelogenous leukemia]] or AML) is said to have occurred. The progression of MDS to [[acute myeloid leukemia|leukemia]] is a good example of the ''[[Knudson hypothesis|multi-step theory of carcinogenesis]]'' in which a series of mutations occur in an initially normal cell and transform it into a [[cancer|cancer cell]].  The mechanism involved was initially thought to be an increase in apoptosis but, as the disease progresses, more cytogenetic damage occurs.  This eventually heralds a decrease in apoptosis leading to leukemia (showing abnormal clones with point mutations in Nras and AML1).
-While recognition of leukemic transformation was historically important (see [[Myelodysplastic syndrome#History|History]]), a significant proportion of the [[morbidity]] and [[death|mortality]] attributable to MDS results not from transformation to [[acute myeloid leukemia|AML]] but rather from the [[cytopenia]]s seen in all MDS patients. While [[anemia]] is the most common [[cytopenia]] in MDS patients, given the ready availability of [[blood transfusion]] MDS patients rarely suffer injury from severe [[anemia]]. However, if an MDS patient is fortunate enough to suffer nothing more than [[anemia]] over several years, they then risk [[iron overload#secondary iron overload|iron overload]]. The two most serious complications in MDS patients resulting from their [[cytopenia]]s are bleeding (due to lack of [[platelet]]s) or infection (due to lack of [[white blood cell]]s).
-The recognition of [[epigenetic]] changes in [[DNA]] structure in MDS has explained the success of two of three commercially available medications approved by the US FDA to treat MDS.   Proper [[DNA methylation]] is critical in the regulation of proliferation genes, and the loss of [[DNA methylation]] control can lead to uncontrolled cell growth, and [[cytopenias]].  The recently approved  DNA methyltransferase inhibitors take advantage of this mechanism by creating a more orderly [[DNA methylation]] profile in the [[hematopoietic stem cell]] [[nucleus]], and thereby restore normal blood counts and retard the progression of MDS to [[acute leukemia]].
-Some authors have proposed that the loss of [[mitochondrial]] function over time leads to the accumulation of DNA [[mutation]]s in hematopoietic stem cells, and this accounts for the increased incidence of MDS in older patients.  Researchers point to the accumulation of [[mitochondrial]] [[iron]] deposits in the [[ringed sideroblast]] as evidence of [[mitochondrial]] dysfunction in MDS.<ref name="pmid12406866">{{cite journal |author=Cazzola M, Invernizzi R, Bergamaschi G, ''et al'' |title=Mitochondrial ferritin expression in erythroid cells from patients with sideroblastic anemia |journal=Blood |volume=101 |issue=5 |pages=1996–2000 |year=2003 |pmid=12406866 |doi=10.1182/blood-2002-07-2006}}</ref>
 ==Pathogenesis==
 ==Genetics==
 ==Associated conditions==
+Myelodysplastic syndrome may be associated with:<ref name=Librepathology>Associations of myelodysplastic syndromes. Librepathology (2015). http://librepathology.org/wiki/index.php/Myelodysplastic_syndromes. Accessed on December 8, 2015</ref>
+*Fanconi syndrome
+*Diamond-blackfan syndrome
+*Shwachman-diamond syndrome
 ==Gross Pathology==
+On gross pathology, a well , subcapsular tumor may be suggestive of myelodysplastic syndrome.<ref name=Librepathology>Associations of myelodysplastic syndromes. Librepathology (2015). http://librepathology.org/wiki/index.php/Myelodysplastic_syndromes. Accessed on December 8, 2015</ref>
 ==Microscopic Pathology==
+On microscopic histopathological analysis, dyserythropoiesis, dysgranulopoiesis, and dysmegakaryocytopoiesis are findings of myelodysplastic syndrome.<ref name=Librepathology>Histologic features of myelodysplastic syndromes. Librepathology (2015). http://librepathology.org/wiki/index.php/Myelodysplastic_syndromes. Accessed on December 8, 2015</ref>
 ===Gallery===
 ==Immunohistochemistry==