HAEM5:Myelodysplastic neoplasm with low blasts and 5q deletion: Difference between revisions

*Macrocytic anemia most common, usually severe and can be transfusion dependent.

*Good prognosis and low risk to progress to AML.

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==Sites of Involvement==

There is no distinct immunophenotypic profile specific for myelodysplastic syndrome (MDS) with isolated del(5q). Currently, morphologic evaluation remains the gold standard in diagnosis of MDS. Immunophenotyping provides supportive evidence to clarify the blasts nature and percentage <ref>{{Cite journal|last=Zini|first=Gina|date=2017|title=Diagnostics and Prognostication of Myelodysplastic Syndromes|url=https://synapse.koreamed.org/DOIx.php?id=10.3343/alm.2017.37.6.465|journal=Annals of Laboratory Medicine|language=en|volume=37|issue=6|pages=465|doi=10.3343/alm.2017.37.6.465|issn=2234-3806|pmc=PMC5587818|pmid=28840983}}</ref>.  

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==Chromosomal Rearrangements (Gene Fusions)==

NA

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* Individual Region Genomic Gain/Loss/LOH

* Characteristic Chromosomal Patterns

<u>Diagnosis:</u>

Lenalidomide is an analogue of thalidomide which functions as an immunomodulatory agent. Treatment with lenalidomide has shown great potential in reducing the abnormal clone as well as transfusion dependency irrespective of cytogenetic complexity <ref>{{Cite journal|last=Giagounidis|first=A. A. N.|last2=Germing|first2=U.|last3=Strupp|first3=C.|last4=Hildebrandt|first4=B.|last5=Heinsch|first5=M.|last6=Aul|first6=C.|date=2005|title=Prognosis of patients with del(5q) MDS and complex karyotype and the possible role of lenalidomide in this patient subgroup|url=http://link.springer.com/10.1007/s00277-005-1054-0|journal=Annals of Hematology|language=en|volume=84|issue=9|pages=569–571|doi=10.1007/s00277-005-1054-0|issn=0939-5555}}</ref><ref>{{Cite journal|last=List|first=Alan|last2=Dewald|first2=Gordon|last3=Bennett|first3=John|last4=Giagounidis|first4=Aristotle|last5=Raza|first5=Azra|last6=Feldman|first6=Eric|last7=Powell|first7=Bayard|last8=Greenberg|first8=Peter|last9=Thomas|first9=Deborah|date=2006|title=Lenalidomide in the Myelodysplastic Syndrome with Chromosome 5q Deletion|url=http://www.nejm.org/doi/abs/10.1056/NEJMoa061292|journal=New England Journal of Medicine|language=en|volume=355|issue=14|pages=1456–1465|doi=10.1056/NEJMoa061292|issn=0028-4793}}</ref>.  FDA approved [https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021880s028lbl.pdf Lenalidomide] on December 2005 for treating  MDS with del(5q) with or without additional cytogenetic abnormalities.

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==Individual Region Genomic Gain / Loss / LOH==

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==Characteristic Chromosomal Patterns==

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The most characteristic cytogenetic abnormality is an interstitial deletion on the long arm of chromosome 5 or del(5q)<ref name=":0">{{Cite journal|last=Van Den Berghe|first=Herman|last2=Cassiman|first2=Jean-Jacques|last3=David|first3=Guido|last4=Fryns|first4=Jean-Pierre|last5=Michaux|first5=Jean-Louis|last6=Sokal|first6=Gerard|date=1974|title=Distinct haematological disorder with deletion of long arm of No. 5 chromosome|url=http://www.nature.com/articles/251437a0|journal=Nature|language=en|volume=251|issue=5474|pages=437–438|doi=10.1038/251437a0|issn=0028-0836}}</ref>  The break point is not fixed but the region between bands q31 and q33 is generally deleted. Several candidates genes were thought to contribute to the haploinsufficiency effect of the deleted region, including ''RPS14'' <ref>{{Cite journal|last=Ebert|first=Benjamin L.|last2=Pretz|first2=Jennifer|last3=Bosco|first3=Jocelyn|last4=Chang|first4=Cindy Y.|last5=Tamayo|first5=Pablo|last6=Galili|first6=Naomi|last7=Raza|first7=Azra|last8=Root|first8=David E.|last9=Attar|first9=Eyal|date=2008|title=Identification of RPS14 as a 5q- syndrome gene by RNA interference screen|url=http://www.nature.com/articles/nature06494|journal=Nature|language=en|volume=451|issue=7176|pages=335–339|doi=10.1038/nature06494|issn=0028-0836|pmc=PMC3771855|pmid=18202658}}</ref>'', CSNK1A1'' <ref name=":1">{{Cite journal|last=Schneider|first=Rebekka K.|last2=Ademà|first2=Vera|last3=Heckl|first3=Dirk|last4=Järås|first4=Marcus|last5=Mallo|first5=Mar|last6=Lord|first6=Allegra M.|last7=Chu|first7=Lisa P.|last8=McConkey|first8=Marie E.|last9=Kramann|first9=Rafael|date=2014|title=Role of Casein Kinase 1A1 in the Biology and Targeted Therapy of del(5q) MDS|url=https://linkinghub.elsevier.com/retrieve/pii/S1535610814003353|journal=Cancer Cell|language=en|volume=26|issue=4|pages=509–520|doi=10.1016/j.ccr.2014.08.001|pmc=PMC4199102|pmid=25242043}}</ref>'','' miR-145 and miR-146a <ref>{{Cite journal|last=Starczynowski|first=Daniel T|last2=Kuchenbauer|first2=Florian|last3=Argiropoulos|first3=Bob|last4=Sung|first4=Sandy|last5=Morin|first5=Ryan|last6=Muranyi|first6=Andrew|last7=Hirst|first7=Martin|last8=Hogge|first8=Donna|last9=Marra|first9=Marco|date=2010|title=Identification of miR-145 and miR-146a as mediators of the 5q– syndrome phenotype|url=http://www.nature.com/articles/nm.2054|journal=Nature Medicine|language=en|volume=16|issue=1|pages=49–58|doi=10.1038/nm.2054|issn=1078-8956}}</ref>. Identification of del(5q) has clinical significance because patients with this cytogenetic abnormality have a good prognosis and they respond well to lenalidomide treatment.     

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==Gene Mutations (SNV / INDEL)==

Somatic mutations in ''JAK2'' and ''MPL'' have been reported in a small subset patients with isolated del(5q), but these mutations seem not confer diagnostic or prognostic value <ref>{{Cite journal|last=Patnaik|first=M M|last2=Lasho|first2=T L|last3=Finke|first3=C M|last4=Gangat|first4=N|last5=Caramazza|first5=D|last6=Holtan|first6=S G|last7=Pardanani|first7=A|last8=Knudson|first8=R A|last9=Ketterling|first9=R P|date=2010|title=WHO-defined ‘myelodysplastic syndrome with isolated del(5q)’ in 88 consecutive patients: survival data, leukemic transformation rates and prevalence of JAK2, MPL and IDH mutations|url=http://www.nature.com/articles/leu2010105|journal=Leukemia|language=en|volume=24|issue=7|pages=1283–1289|doi=10.1038/leu.2010.105|issn=0887-6924|pmc=PMC3035970|pmid=20485371}}</ref>. A subset of cases could have ''[[SF3B1]]'' mutations, which needs to be differentiated with MDS-RS.

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==Epigenomic Alterations==

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Several candidate genes in the common deleted region of 5q have been reported to contribute to the molecular pathogenesis.

miR-145 and miR146α: These two micro RNA genes are thought to be associated with thrombocytosis and hypolobulated megakaryocytes <ref>{{Cite journal|last=Starczynowski|first=Daniel T|last2=Kuchenbauer|first2=Florian|last3=Argiropoulos|first3=Bob|last4=Sung|first4=Sandy|last5=Morin|first5=Ryan|last6=Muranyi|first6=Andrew|last7=Hirst|first7=Martin|last8=Hogge|first8=Donna|last9=Marra|first9=Marco|date=2010|title=Identification of miR-145 and miR-146a as mediators of the 5q– syndrome phenotype|url=http://www.nature.com/articles/nm.2054|journal=Nature Medicine|language=en|volume=16|issue=1|pages=49–58|doi=10.1038/nm.2054|issn=1078-8956}}</ref>.   

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==Genetic Diagnostic Testing Methods==