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==Primary Author(s)== Xiaoli Du, Ph.D; Teresa A. Smolarek, Ph.D, FACMG Division of Human Genetics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, C..."

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Created page with " ==Primary Author(s)== Xiaoli Du, Ph.D; Teresa A. Smolarek, Ph.D, FACMG Division of Human Genetics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, C..."

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==Primary Author(s)==
Xiaoli Du, Ph.D; Teresa A. Smolarek, Ph.D, FACMG

Division of Human Genetics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH, 45229, USA.

__TOC__

==Cancer Category/Type==

Myelodysplastic Syndrome

==Cancer Sub-Classification / Subtype==

Myelodysplastic Syndrome with excess blasts (MDS-EB)

==Definition / Description of Disease==

Myelodysplastic syndrome (MDS) with excess blasts (EB) is a category of MDS characterized by <20% blasts in both peripheral blood and bone marrow. MDS-EB type 1 (MDS-EB-1) is classified as <5% blasts in the blood and <10% blasts in the bone marrow. MDS-EB type 2 (MDS-EB-2) is classified as 5-19% blasts in the blood and 10-19% blasts in the bone marrow with the presence of Auer rods<ref>{{Cite journal|last=Greenberg|first=P.|last2=Cox|first2=C.|last3=LeBeau|first3=M. M.|last4=Fenaux|first4=P.|last5=Morel|first5=P.|last6=Sanz|first6=G.|last7=Sanz|first7=M.|last8=Vallespi|first8=T.|last9=Hamblin|first9=T.|date=1997-03-15|title=International scoring system for evaluating prognosis in myelodysplastic syndromes|url=https://pubmed.ncbi.nlm.nih.gov/9058730|journal=Blood|volume=89|issue=6|pages=2079–2088|issn=0006-4971|pmid=9058730}}</ref><ref>{{Cite journal|last=Germing|first=Ulrich|last2=Strupp|first2=Corinna|last3=Kuendgen|first3=Andrea|last4=Aivado|first4=Manuel|last5=Giagounidis|first5=Aristoteles|last6=Hildebrandt|first6=Barbara|last7=Aul|first7=Carlo|last8=Haas|first8=Rainer|last9=Gattermann|first9=Norbert|date=2006-01|title=Refractory anaemia with excess of blasts (RAEB): analysis of reclassification according to the WHO proposals|url=https://pubmed.ncbi.nlm.nih.gov/16398650|journal=British Journal of Haematology|volume=132|issue=2|pages=162–167|doi=10.1111/j.1365-2141.2005.05853.x|issn=0007-1048|pmid=16398650}}</ref>. The category of erythroid/myeloid-type acute erythroid leukemia in the 2008 WHO classification is now categorized as MDS-EB<ref name=":0">Arber DA, et al., (2016). WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J Editors. IARC Press: Lyon, France, p106-109.</ref>. In addition, the majority of myelodysplastic syndrome with marrow fibrosis (MDS-F) belongs to myelodysplastic syndrome with excess blasts and fibrosis (MDS-EB-F)<ref>{{Cite journal|last=Lambertenghi-Deliliers|first=G.|last2=Orazi|first2=A.|last3=Luksch|first3=R.|last4=Annaloro|first4=C.|last5=Soligo|first5=D.|date=1991-06|title=Myelodysplastic syndrome with increased marrow fibrosis: a distinct clinico-pathological entity|url=https://pubmed.ncbi.nlm.nih.gov/1712222|journal=British Journal of Haematology|volume=78|issue=2|pages=161–166|doi=10.1111/j.1365-2141.1991.tb04411.x|issn=0007-1048|pmid=1712222}}</ref><ref>{{Cite journal|last=Bae|first=E.|last2=Park|first2=C.-J.|last3=Cho|first3=Y.-U.|last4=Seo|first4=E.-J.|last5=Chi|first5=H.-S.|last6=Jang|first6=S.|last7=Lee|first7=K.-H.|last8=Lee|first8=J.-H.|last9=Lee|first9=J.-H.|date=2013-12|title=Differential diagnosis of myelofibrosis based on WHO 2008 criteria: acute panmyelosis with myelofibrosis, acute megakaryoblastic leukemia with myelofibrosis, primary myelofibrosis and myelodysplastic syndrome with myelofibrosis|url=https://pubmed.ncbi.nlm.nih.gov/23693053|journal=International Journal of Laboratory Hematology|volume=35|issue=6|pages=629–636|doi=10.1111/ijlh.12101|issn=1751-553X|pmid=23693053}}</ref><ref>{{Cite journal|last=Orazi|first=Attilio|date=2007|title=Histopathology in the diagnosis and classification of acute myeloid leukemia, myelodysplastic syndromes, and myelodysplastic/myeloproliferative diseases|url=https://pubmed.ncbi.nlm.nih.gov/17587881|journal=Pathobiology: Journal of Immunopathology, Molecular and Cellular Biology|volume=74|issue=2|pages=97–114|doi=10.1159/000101709|issn=1015-2008|pmid=17587881}}</ref>.

==Synonyms / Terminology==

Refractory anemia with excess blasts, erythroid/myeloid-type acute erythroid leukemia

==Epidemiology / Prevalence==

MDS-EB accounts for 40% of all cases of MDS (Arber DA, et al., (2016).)

*Occurs mainly in patients aged greater than 50 years old

==Clinical Features==

The clinical features are often nonspecific and are generally related to the corresponding cytopenias such as anemia, thrombocytopenia and neutropenia. The recommended thresholds for cytopenia suggested by International Prognostic Scoring System (IPSS) (PMID: 22740453) include:

*Hemoglobin concentration: <10 g/dL
*Absolute neutrophil count: <1.8 x109/L AND
*Platelet count: <100 x109/L

==Sites of Involvement==

Peripheral blood and bone marrow

==Morphologic Features==

The morphologic features of the peripheral blood and bone marrow are currently the gold standard for the diagnosis of MDS<ref name=":0" />.
{| class="wikitable"
|+
!'''Categories'''
!'''Morphologic Features'''
|-
|Blood
|Abnormalities in all three myeloid cell lines; blasts commonly present
|-
| rowspan="3" |Bone marrow

*Often hypercellular
*Blasts aggregated
|Erythropoiesis: erythropoiesis increased, dyserythropoiesis: abnormally lobated nuclei, internuclear bridging
|-
|Granulopoiesis: dysplasia, nuclear hyposegmentation or hypersegmented nuclei or cytoplasmic hypogranularity
|-
|Dysmegakaryopoiesis: micromegakaryocytes often seen; multiple widely separated nuclei also can occur
|}

==Immunophenotype==

Put your text here and/or fill in the table

{| class="wikitable sortable"
|-
!Finding!!Marker
|-
|'''Positive (universal)'''
|CD34 and/or KIT (CD117), CD38, HLA-DR and CD13 and/or CD33
|-
|'''Positive (subset)'''
|CD7 (20%), CD56 (10%)
|}

==Chromosomal Rearrangements (Gene Fusions)==

None
==Characteristic Chromosomal Aberrations / Patterns==

Gain of chromosome 8, del(5q) or t(5q), monosomy 7, del(7q), del(20q), complex karyotype

==Genomic Gain/Loss/LOH==

*Nonspecific cytogenetic abnormalities have been observed in 30-50% of MDS-EB cases.
*Gain of chromosome 8, del(5q) or t(5q), monosomy 7, del(7q), del(20q), complex karyotype<ref>{{Cite journal|last=Germing|first=Ulrich|last2=Strupp|first2=Corinna|last3=Kuendgen|first3=Andrea|last4=Isa|first4=Shadi|last5=Knipp|first5=Sabine|last6=Hildebrandt|first6=Barbara|last7=Giagounidis|first7=Aristoteles|last8=Aul|first8=Carlo|last9=Gattermann|first9=Norbert|date=2006-12|title=Prospective validation of the WHO proposals for the classification of myelodysplastic syndromes|url=https://pubmed.ncbi.nlm.nih.gov/17145595|journal=Haematologica|volume=91|issue=12|pages=1596–1604|issn=1592-8721|pmid=17145595}}</ref>.

==Gene Mutations (SNV/INDEL)==

Most frequent mutations: ''SRSF2, IDH1, IDH2, ASXL1, CBL, RUNX1, RAS''
===Other Mutations===
None

==Epigenomics (Methylation)==

No

==Genes and Main Pathways Involved==

*''SRSF2'': involved in pre-mRNA splicing
*''IDH1/IDH2'': involved in hypoxia pathways
*''ASXL1'': involved in chromatin remodeling
*''CBL'': involved in targeting substrates for degradation by the proteasome
*''RUNX1'': transcription factor for hematopoiesis cells
*''RAS'': involved in RAS/MAPK pathway

==Diagnostic Testing Methods==

*Quantification of dysplasia: Microscopy
*Pathology: Immunophenotyping by flow cytometry
*Genetics: Conventional karyotyping. Fluorescence in situ hybridization (FISH) analysis, microarray and sequencing

==Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)==

*Diagnosis: 2-19% blasts in peripheral blood or 5-19% myeloblasts in bone marrow
*Prognosis: Patients with MDS-EB-1 have a median survival of 16 months with 25% cases progressing to AML. While patients with MDS-EB-2 have a median survival of 9 months with 33% cases progressing to AML<ref>{{Cite journal|last=Germing|first=Ulrich|last2=Strupp|first2=Corinna|last3=Kuendgen|first3=Andrea|last4=Isa|first4=Shadi|last5=Knipp|first5=Sabine|last6=Hildebrandt|first6=Barbara|last7=Giagounidis|first7=Aristoteles|last8=Aul|first8=Carlo|last9=Gattermann|first9=Norbert|date=2006-12|title=Prospective validation of the WHO proposals for the classification of myelodysplastic syndromes|url=https://pubmed.ncbi.nlm.nih.gov/17145595|journal=Haematologica|volume=91|issue=12|pages=1596–1604|issn=1592-8721|pmid=17145595}}</ref><ref>{{Cite journal|last=Strupp|first=Corinna|last2=Gattermann|first2=Norbert|last3=Giagounidis|first3=Aristoteles|last4=Aul|first4=Carlo|last5=Hildebrandt|first5=Barbara|last6=Haas|first6=Rainer|last7=Germing|first7=Ulrich|date=2003-05|title=Refractory anemia with excess of blasts in transformation: analysis of reclassification according to the WHO proposals|url=https://pubmed.ncbi.nlm.nih.gov/12620291|journal=Leukemia Research|volume=27|issue=5|pages=397–404|doi=10.1016/s0145-2126(02)00220-5|issn=0145-2126|pmid=12620291}}</ref><ref>{{Cite journal|last=Amin|first=H. M.|last2=Yang|first2=Y.|last3=Shen|first3=Y.|last4=Estey|first4=E. H.|last5=Giles|first5=F. J.|last6=Pierce|first6=S. A.|last7=Kantarjian|first7=H. M.|last8=O'Brien|first8=S. M.|last9=Jilani|first9=I.|date=2005-09|title=Having a higher blast percentage in circulation than bone marrow: clinical implications in myelodysplastic syndrome and acute lymphoid and myeloid leukemias|url=https://pubmed.ncbi.nlm.nih.gov/16049515|journal=Leukemia|volume=19|issue=9|pages=1567–1572|doi=10.1038/sj.leu.2403876|issn=0887-6924|pmid=16049515}}</ref>. ''TP53, RUNX1 or ASXL1'' mutations are associated with poor prognosis in MDS-EB with erythroid predominance<ref>{{Cite journal|last=Grossmann|first=V.|last2=Bacher|first2=U.|last3=Haferlach|first3=C.|last4=Schnittger|first4=S.|last5=Pötzinger|first5=F.|last6=Weissmann|first6=S.|last7=Roller|first7=A.|last8=Eder|first8=C.|last9=Fasan|first9=A.|date=2013-09|title=Acute erythroid leukemia (AEL) can be separated into distinct prognostic subsets based on cytogenetic and molecular genetic characteristics|url=https://pubmed.ncbi.nlm.nih.gov/23648669|journal=Leukemia|volume=27|issue=9|pages=1940–1943|doi=10.1038/leu.2013.144|issn=1476-5551|pmid=23648669}}</ref><ref>{{Cite journal|last=Hasserjian|first=Robert P.|last2=Zuo|first2=Zhuang|last3=Garcia|first3=Christine|last4=Tang|first4=Guilin|last5=Kasyan|first5=Armen|last6=Luthra|first6=Rajyalakshmi|last7=Abruzzo|first7=Lynne V.|last8=Kantarjian|first8=Hagop M.|last9=Medeiros|first9=L. Jeffrey|date=2010-03-11|title=Acute erythroid leukemia: a reassessment using criteria refined in the 2008 WHO classification|url=https://pubmed.ncbi.nlm.nih.gov/20040759|journal=Blood|volume=115|issue=10|pages=1985–1992|doi=10.1182/blood-2009-09-243964|issn=1528-0020|pmc=2942006|pmid=20040759}}</ref>.
*Therapeutic: Hematopoietic stem cell transplantation (HSCT) is the therapy of choice for MDS-EB in childhood with the best available donor<ref>{{Cite journal|last=Hasle|first=Henrik|date=2016-12-02|title=Myelodysplastic and myeloproliferative disorders of childhood|url=https://pubmed.ncbi.nlm.nih.gov/27913534|journal=Hematology. American Society of Hematology. Education Program|volume=2016|issue=1|pages=598–604|doi=10.1182/asheducation-2016.1.598|issn=1520-4383|pmc=6142519|pmid=27913534}}</ref>. Azacitidine, a DNA methyltransferase-inhibitor, has been reported to increase the overall survival for adult patients with high-risk MDS (MDS-REB) in comparison with conventional care<ref>{{Cite journal|last=Gore|first=Steven D.|last2=Fenaux|first2=Pierre|last3=Santini|first3=Valeria|last4=Bennett|first4=John M.|last5=Silverman|first5=Lewis R.|last6=Seymour|first6=John F.|last7=Hellström-Lindberg|first7=Eva|last8=Swern|first8=Arlene S.|last9=Beach|first9=Charles L.|date=2013-07|title=A multivariate analysis of the relationship between response and survival among patients with higher-risk myelodysplastic syndromes treated within azacitidine or conventional care regimens in the randomized AZA-001 trial|url=https://pubmed.ncbi.nlm.nih.gov/23585522|journal=Haematologica|volume=98|issue=7|pages=1067–1072|doi=10.3324/haematol.2012.074831|issn=1592-8721|pmc=3696610|pmid=23585522}}</ref>.

==Familial Forms==

No

==Other Information==

No

==Links==

Put your links here (use link icon at top of page)

==References==
<references />

#

==Notes==
<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page. If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage). Additional global feedback or concerns are also welcome.

HAEM4Backup:Myelodysplastic Syndrome (MDS) with Excess Blasts - Revision history

Bailey.Glen: Created page with " ==Primary Author(s)== Xiaoli Du, Ph.D; Teresa A. Smolarek, Ph.D, FACMG Division of Human Genetics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, C..."

Bailey.Glen: Created page with "
==Primary Author(s)== Xiaoli Du, Ph.D; Teresa A. Smolarek, Ph.D, FACMG Division of Human Genetics, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, C..."