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

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

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==Primary Author(s)*==

Xiaoli Du, Ph.D; Teresa 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 (MDS) with Single Lineage Dysplasia (SLD)

==Definition / Description of Disease==

Myelodysplastic syndrome (MDS) with single lineage dysplasia (SLD) is a category of MDS characterized by unexplained cytopenia or bi-cytopenia, ≥10% dysplastic cells in one myeloid lineage (red blood cells, white blood cells, or megakaryocytes), <5% of blasts in bone marrow and <1% blasts in peripheral blood, non-Auer rods, <15% ring sideroblasts in bone marrow or <5% if ''SF3B1'' mutation is present <ref name=":0">{{Cite journal|last=Arber|first=Daniel A.|last2=Orazi|first2=Attilio|last3=Hasserjian|first3=Robert|last4=Thiele|first4=Jürgen|last5=Borowitz|first5=Michael J.|last6=Le Beau|first6=Michelle M.|last7=Bloomfield|first7=Clara D.|last8=Cazzola|first8=Mario|last9=Vardiman|first9=James W.|date=2016-05-19|title=The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia|url=https://pubmed.ncbi.nlm.nih.gov/27069254|journal=Blood|volume=127|issue=20|pages=2391–2405|doi=10.1182/blood-2016-03-643544|issn=1528-0020|pmid=27069254}}</ref>. MDS-SLD has a low risk of progression or transformation to acute myeloid leukemia and often follow a prolonged/ indolent clinical course. The presence of blasts in the peripheral blood excludes a diagnosis of MDS-SLD <ref>{{Cite journal|last=Gyan|first=Emmanuel|last2=Dreyfus|first2=François|last3=Fenaux|first3=Pierre|date=2015|title=Refractory thrombocytopenia and neutropenia: a diagnostic challenge|url=https://pubmed.ncbi.nlm.nih.gov/25745545|journal=Mediterranean Journal of Hematology and Infectious Diseases|volume=7|issue=1|pages=e2015018|doi=10.4084/MJHID.2015.018|issn=2035-3006|pmc=4344166|pmid=25745545}}</ref>. It is essential to exclude all possible non-clonal etiologies for the abnormalities such as: possible vitamin B12 or folic acid deficiency, copper deficiency, excessive zinc supplementation or paroxysmal nocturnal hemoglobinuria<ref>{{Cite journal|last=Gregg|first=Xylina T.|last2=Reddy|first2=Vishnu|last3=Prchal|first3=Josef T.|date=2002-08-15|title=Copper deficiency masquerading as myelodysplastic syndrome|url=https://pubmed.ncbi.nlm.nih.gov/12149237|journal=Blood|volume=100|issue=4|pages=1493–1495|doi=10.1182/blood-2002-01-0256|issn=0006-4971|pmid=12149237}}</ref> <ref>{{Cite journal|last=Irving|first=Julie A.|last2=Mattman|first2=Andre|last3=Lockitch|first3=Gillian|last4=Farrell|first4=Kevin|last5=Wadsworth|first5=Louis D.|date=2003-07-22|title=Element of caution: a case of reversible cytopenias associated with excessive zinc supplementation|url=https://pubmed.ncbi.nlm.nih.gov/12874162|journal=CMAJ: Canadian Medical Association journal = journal de l'Association medicale canadienne|volume=169|issue=2|pages=129–131|issn=0820-3946|pmc=PMC164980|pmid=12874162}}</ref>. Persistent cytopenia without morphological evidence of dysplasia or MDS-defining cytogenetic abnormalities should not be diagnosed as MDS-SLD. Without definitive morphological and/or cytogenetic evidence, it is recommended that the patient be observed for >=6 months before establishing the definitive diagnosis<ref name=":0" />.

==Synonyms / Terminology==

Refractory cytopenia with unilineage dysplasia (RCUD), MDS-SLD

==Epidemiology / Prevalence==

MDS-SLD accounts for 7-20% of all cases of MDS<ref name=":0" /> <ref>{{Cite journal|last=Della Porta|first=M. G.|last2=Travaglino|first2=E.|last3=Boveri|first3=E.|last4=Ponzoni|first4=M.|last5=Malcovati|first5=L.|last6=Papaemmanuil|first6=E.|last7=Rigolin|first7=G. M.|last8=Pascutto|first8=C.|last9=Croci|first9=G.|date=2015-01|title=Minimal morphological criteria for defining bone marrow dysplasia: a basis for clinical implementation of WHO classification of myelodysplastic syndromes|url=https://pubmed.ncbi.nlm.nih.gov/24935723|journal=Leukemia|volume=29|issue=1|pages=66–75|doi=10.1038/leu.2014.161|issn=1476-5551|pmid=24935723}}</ref><ref>{{Cite journal|last=Germing|first=Ulrich|last2=Strupp|first2=Corinna|last3=Giagounidis|first3=Aristoteles|last4=Haas|first4=Rainer|last5=Gattermann|first5=Norbert|last6=Starke|first6=Carsten|last7=Aul|first7=Carlo|date=2012-06|title=Evaluation of dysplasia through detailed cytomorphology in 3156 patients from the Düsseldorf Registry on myelodysplastic syndromes|url=https://pubmed.ncbi.nlm.nih.gov/22421409|journal=Leukemia Research|volume=36|issue=6|pages=727–734|doi=10.1016/j.leukres.2012.02.014|issn=1873-5835|pmid=22421409}}</ref>.

*Occurs mainly in older patients
*Median age is 65-70 years
*No significant sex predilection

==Clinical Features==

The clinical phenotypes are often nonspecific and are generally related to the corresponding cytopenia. The recommended thresholds for cytopenia suggested by International Prognostic Scoring System (IPSS) <ref>{{Cite journal|last=Greenberg|first=Peter L.|last2=Tuechler|first2=Heinz|last3=Schanz|first3=Julie|last4=Sanz|first4=Guillermo|last5=Garcia-Manero|first5=Guillermo|last6=Solé|first6=Francesc|last7=Bennett|first7=John M.|last8=Bowen|first8=David|last9=Fenaux|first9=Pierre|date=2012-09-20|title=Revised international prognostic scoring system for myelodysplastic syndromes|url=https://pubmed.ncbi.nlm.nih.gov/22740453|journal=Blood|volume=120|issue=12|pages=2454–2465|doi=10.1182/blood-2012-03-420489|issn=1528-0020|pmc=4425443|pmid=22740453}}</ref>:

*Hemoglobin concentration: <10 g/dL
*Absolute neutrophil count: <1.8 x10<sup>9</sup>/L AND
*Platelet count: <100 x10<sup>9</sup>/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'''
|-
|Dyserythropoiesis
(≥10% of the nucleated erythroid precursors)
|Nuclear budding, internuclear chromatin bridging, multinuclearity, megaloblastoid changes or karyorrhexis
|-
|Neutrophil dysplasia
|Small size, dense chromatin, nuclear hyposegmentation, granulation abnormalities
|-
|Megakaryocytic dysplasia

(≥10% dysplastic megakaryocytes)
|Hypobated or bilobed nuclei, multiple separated nuclei, micromegakaryocytes
|}

==Immunophenotype==

Same as the MDS immunophenotype; however, definitive morphological and/or cytogenetic findings can help establish the diagnosis. MDS-SLD with erythroid dysplasia shows aberrant immunophenotypic features of erythropoietic precursors<ref>{{Cite journal|last=Porwit|first=A.|last2=van de Loosdrecht|first2=A. A.|last3=Bettelheim|first3=P.|last4=Brodersen|first4=L. Eidenschink|last5=Burbury|first5=K.|last6=Cremers|first6=E.|last7=Della Porta|first7=M. G.|last8=Ireland|first8=R.|last9=Johansson|first9=U.|date=2014-09|title=Revisiting guidelines for integration of flow cytometry results in the WHO classification of myelodysplastic syndromes-proposal from the International/European LeukemiaNet Working Group for Flow Cytometry in MDS|url=https://pubmed.ncbi.nlm.nih.gov/24919805|journal=Leukemia|volume=28|issue=9|pages=1793–1798|doi=10.1038/leu.2014.191|issn=1476-5551|pmid=24919805}}</ref>. Some of the cases show aberrant immunophenotypic features in the myelomonocytic compartment or in precursors<ref>{{Cite journal|last=Kern|first=Wolfgang|last2=Haferlach|first2=Claudia|last3=Schnittger|first3=Susanne|last4=Haferlach|first4=Torsten|date=2010-10-01|title=Clinical utility of multiparameter flow cytometry in the diagnosis of 1013 patients with suspected myelodysplastic syndrome: correlation to cytomorphology, cytogenetics, and clinical data|url=https://pubmed.ncbi.nlm.nih.gov/20572043|journal=Cancer|volume=116|issue=19|pages=4549–4563|doi=10.1002/cncr.25353|issn=0008-543X|pmid=20572043}}</ref>.

==Chromosomal Rearrangements (Gene Fusions)==

None
==Characteristic Chromosomal Aberrations / Patterns==

*Del(20q), gain of chromosome 8, abnormalities with chromosome 5 and 7<ref name=":1">{{Cite journal|last=Braun|first=Thorsten|last2=de Botton|first2=Stéphane|last3=Taksin|first3=Anne-Laure|last4=Park|first4=Sophie|last5=Beyne-Rauzy|first5=Odile|last6=Coiteux|first6=Valérie|last7=Sapena|first7=Rosa|last8=Lazareth|first8=Anne|last9=Leroux|first9=Geneviève|date=2011-07|title=Characteristics and outcome of myelodysplastic syndromes (MDS) with isolated 20q deletion: a report on 62 cases|url=https://pubmed.ncbi.nlm.nih.gov/21396711|journal=Leukemia Research|volume=35|issue=7|pages=863–867|doi=10.1016/j.leukres.2011.02.008|issn=1873-5835|pmid=21396711}}</ref>.

==Genomic Gain/Loss/LOH==

*Nonspecific cytogenetic abnormalities have been observed in 50% of MDS-SLD cases.
*Del(20q), gain of chromosome 8, abnormalities with chromosome 5 and 7<ref name=":1" /> .

==Gene Mutations (SNV/INDEL)==

*Somatic mutations have been identified in 60-70% of MDS-SLD cases.
*Most frequent mutations: ''ASXL1, TET2, SF3B1, U2AF1, SRSF2''<ref>{{Cite journal|last=Haferlach|first=T.|last2=Nagata|first2=Y.|last3=Grossmann|first3=V.|last4=Okuno|first4=Y.|last5=Bacher|first5=U.|last6=Nagae|first6=G.|last7=Schnittger|first7=S.|last8=Sanada|first8=M.|last9=Kon|first9=A.|date=2014-02|title=Landscape of genetic lesions in 944 patients with myelodysplastic syndromes|url=https://pubmed.ncbi.nlm.nih.gov/24220272|journal=Leukemia|volume=28|issue=2|pages=241–247|doi=10.1038/leu.2013.336|issn=1476-5551|pmc=3918868|pmid=24220272}}</ref><ref>{{Cite journal|last=Wu|first=Lingyun|last2=Song|first2=Luxi|last3=Xu|first3=Lan|last4=Chang|first4=Chunkang|last5=Xu|first5=Feng|last6=Wu|first6=Dong|last7=He|first7=Qi|last8=Su|first8=Jiying|last9=Zhou|first9=Liyu|date=2016-04|title=Genetic landscape of recurrent ASXL1, U2AF1, SF3B1, SRSF2, and EZH2 mutations in 304 Chinese patients with myelodysplastic syndromes|url=https://pubmed.ncbi.nlm.nih.gov/26508027|journal=Tumour Biology: The Journal of the International Society for Oncodevelopmental Biology and Medicine|volume=37|issue=4|pages=4633–4640|doi=10.1007/s13277-015-4305-2|issn=1423-0380|pmid=26508027}}</ref><ref>{{Cite journal|last=Tefferi|first=Ayalew|last2=Lasho|first2=Terra L.|last3=Patnaik|first3=Mrinal M.|last4=Saeed|first4=Lyla|last5=Mudireddy|first5=Mythri|last6=Idossa|first6=Dame|last7=Finke|first7=Christy|last8=Ketterling|first8=Rhett P.|last9=Pardanani|first9=Animesh|date=2017-12|title=Targeted next-generation sequencing in myelodysplastic syndromes and prognostic interaction between mutations and IPSS-R|url=https://pubmed.ncbi.nlm.nih.gov/28875545|journal=American Journal of Hematology|volume=92|issue=12|pages=1311–1317|doi=10.1002/ajh.24901|issn=1096-8652|pmid=28875545}}</ref>.

===Other Mutations===
None

==Epigenomics (Methylation)==

DNA methylation genes ''DNMT3A, TET2, IDH1'', and ''IDH2'' are associated with MDS or excess blasts<ref>{{Cite journal|last=Malcovati|first=Luca|last2=Papaemmanuil|first2=Elli|last3=Ambaglio|first3=Ilaria|last4=Elena|first4=Chiara|last5=Gallì|first5=Anna|last6=Della Porta|first6=Matteo G.|last7=Travaglino|first7=Erica|last8=Pietra|first8=Daniela|last9=Pascutto|first9=Cristiana|date=2014-08-28|title=Driver somatic mutations identify distinct disease entities within myeloid neoplasms with myelodysplasia|url=https://pubmed.ncbi.nlm.nih.gov/24970933|journal=Blood|volume=124|issue=9|pages=1513–1521|doi=10.1182/blood-2014-03-560227|issn=1528-0020|pmc=4148773|pmid=24970933}}</ref>.

==Genes and Main Pathways Involved==

*''ASXL1'': involved in chromatin remodeling
*''TET2'': involved in regulating transcription
*''SF3B1'': involved in pre-mRNA splicing

==Diagnostic Testing Methods==

*Quantification of dysplasia: Microscopy
*Pathology: Immunophenotyping by flow cytometry
*Genetics: Conventional karyotyping and sequencing

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

*Diagnosis: Cytopenia or biocytopenia, ≥10% dysplastic cells in one myeloid lineage and exclude the non-clonal causes of dysplasia.
*Prognosis: International Prognostic Scoring System (IPSS) was adopted and was accepted by the Myelodysplastic Syndrome Working Group<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>. The majority of patients with a diagnosis of MDS-SLD fall into the low-risk and intermediate-1–risk groups. Median survival of patients with MDS-SLD is approximately 66 months with the rate of progression to acute myeloid leukemia of 10% at 5 years<ref>{{Cite journal|last=Maassen|first=Anna|last2=Strupp|first2=Corinna|last3=Giagounidis|first3=Aristoteles|last4=Kuendgen|first4=Andrea|last5=Nachtkamp|first5=Kathrin|last6=Hildebrandt|first6=Barbara|last7=Gattermann|first7=Norbert|last8=Aul|first8=Carlo|last9=Haas|first9=Rainer|date=2013-01|title=Validation and proposals for a refinement of the WHO 2008 classification of myelodysplastic syndromes without excess of blasts|url=https://pubmed.ncbi.nlm.nih.gov/23122806|journal=Leukemia Research|volume=37|issue=1|pages=64–70|doi=10.1016/j.leukres.2012.09.021|issn=1873-5835|pmid=23122806}}</ref> .
*Therapeutic: The presence of ''SF3B1'' somatic mutation is an unfavorable marker of response to Immunosuppressive Therapy<ref>{{Cite journal|last=Zhang|first=Qing|last2=Haider|first2=Mintallah|last3=Al Ali|first3=Najla H.|last4=Lancet|first4=Jeffrey E.|last5=Epling-Burnette|first5=Pearlie K.|last6=List|first6=Alan F.|last7=Padron|first7=Eric|last8=Komrokji|first8=Rami S.|date=2020-06|title=SF3B1 Mutations Negatively Predict for Response to Immunosuppressive Therapy in Myelodysplastic Syndromes|url=https://pubmed.ncbi.nlm.nih.gov/32179032|journal=Clinical Lymphoma, Myeloma & Leukemia|volume=20|issue=6|pages=400–406.e2|doi=10.1016/j.clml.2019.12.023|issn=2152-2669|pmc=7771378|pmid=32179032}}</ref>. MDS-SLD has been reported to be associated with autoimmune disorders such as autoimmune hemolytic anemia<ref name=":2">{{Cite journal|last=Grignano|first=Eric|last2=Jachiet|first2=Vincent|last3=Fenaux|first3=Pierre|last4=Ades|first4=Lionel|last5=Fain|first5=Olivier|last6=Mekinian|first6=Arsène|date=2018-11|title=Autoimmune manifestations associated with myelodysplastic syndromes|url=https://pubmed.ncbi.nlm.nih.gov/30091023|journal=Annals of Hematology|volume=97|issue=11|pages=2015–2023|doi=10.1007/s00277-018-3472-9|issn=1432-0584|pmid=30091023}}</ref>. Steroids and immunosuppressive treatment (IST) remain the first-line treatment. However, due to the steroid dependence or relapse occurs in 50 to 70% of cases, accumulating evidence suggests that hypomethylating agents may be effective in treating these complications for the underlying MDS<ref name=":2" />.

==Familial Forms==

None

==Other Information==

None

==Links==

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

==References==
<references />
===EXAMPLE Book===

#''Arber, Daniel A.; et al. (2016).'' "The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia"''. Blood.'' '''127''' ''(20): 2391–2405.'' doi'':''10.1182/blood-2016-03-643544''.'' ISSN 1528-0020''.'' <nowiki>PMID 27069254</nowiki>
#Arber DA, et al., (2017). Acute myeloid leukaemia with recurrent genetic abnormalities, in World Health Organization 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, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. IARC Press: Lyon, France, p129-171.

==Notes==
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HAEM4Backup:Myelodysplastic Syndrome (MDS) with Single Lineage Dysplasia - Revision history

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