HAEM5:Acute myeloid leukaemia with DEK::NUP214 fusion: Difference between revisions

Usually presents with anemia and thrombocytopenia and often with pancytopenia.  In adults, the median white blood cell count is 12x10^9/L, which is generally lower than other AML types<ref name=":0" />.

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==Sites of Involvement==

This AML subtype is classified based on the presence of a t(6;9)(p23;q34.1), which results in fusion of the 5’ portion of ''DEK'' at “6p23” (specifically 6p22.3[hg38]) and the 3’ portion of ''NUP214''(''CAN'') at “9q34.1” (specifically 9q34.13[hg38]).  The breakpoints are intronic, producing an in-frame fusion<ref>{{Cite journal|last=von Lindern|first=M.|last2=Fornerod|first2=M.|last3=van Baal|first3=S.|last4=Jaegle|first4=M.|last5=de Wit|first5=T.|last6=Buijs|first6=A.|last7=Grosveld|first7=G.|date=1992|title=The translocation (6;9), associated with a specific subtype of acute myeloid leukemia, results in the fusion of two genes, dek and can, and the expression of a chimeric, leukemia-specific dek-can mRNA|url=https://www.ncbi.nlm.nih.gov/pubmed/1549122|journal=Molecular and Cellular Biology|volume=12|issue=4|pages=1687–1697|doi=10.1128/mcb.12.4.1687|issn=0270-7306|pmc=PMC369612|pmid=1549122}}</ref>.  The ''DEK''-''NUP214'' fusion present on the derivative chromosome 6 is considered the pathogenic entity as the reciprocal ''NUP214''-''DEK'' fusion on chromosome 9 does not appear to be transcribed<ref>{{Cite journal|last=von Lindern|first=M.|last2=Fornerod|first2=M.|last3=Soekarman|first3=N.|last4=van Baal|first4=S.|last5=Jaegle|first5=M.|last6=Hagemeijer|first6=A.|last7=Bootsma|first7=D.|last8=Grosveld|first8=G.|date=1992|title=Translocation t(6;9) in acute non-lymphocytic leukaemia results in the formation of a DEK-CAN fusion gene|url=https://www.ncbi.nlm.nih.gov/pubmed/1308167|journal=Bailliere's Clinical Haematology|volume=5|issue=4|pages=857–879|doi=10.1016/s0950-3536(11)80049-1|issn=0950-3536|pmid=1308167}}</ref>.  Typically the ''DEK''-''NUP214'' fusion presents as the sole abnormality but can be part of a complex karyotype<ref name=":0" />.

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* Individual Region Genomic Gain/Loss/LOH

* Characteristic Chromosomal Patterns

This translocation has traditionally been associated with a poor prognosis in both adult and pediatric cases<ref name=":0" />.  Of note, a 2014 retrospective analysis suggests a better outcome for pediatric patients with this translocation than previously reported<ref>{{Cite journal|last=Sandahl|first=Julie Damgaard|last2=Coenen|first2=Eva A.|last3=Forestier|first3=Erik|last4=Harbott|first4=Jochen|last5=Johansson|first5=Bertil|last6=Kerndrup|first6=Gitte|last7=Adachi|first7=Souichi|last8=Auvrignon|first8=Anne|last9=Beverloo|first9=H. Berna|date=2014|title=t(6;9)(p22;q34)/DEK-NUP214-rearranged pediatric myeloid leukemia: an international study of 62 patients|url=https://www.ncbi.nlm.nih.gov/pubmed/24441146|journal=Haematologica|volume=99|issue=5|pages=865–872|doi=10.3324/haematol.2013.098517|issn=1592-8721|pmc=4008104|pmid=24441146}}</ref>.  Elevated white blood cell counts and higher bone marrow blast percentages are associated with shorter periods of overall survival and disease-free survival, respectively<ref name=":0" />.

Cases with the 6;9 translocation and <20% blasts are not currently classified as AML, which is controversial.  Such cases should have close follow-up to monitor for development of more definitive evidence of AML or may be treated as AML if clinically appropriate<ref name=":0" />.

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

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Not applicable

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==Characteristic Chromosomal Patterns==

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Not applicable

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==Gene Mutations (SNV / INDEL)==

COSMIC does not have specific information on mutations related to this subtype of AML.

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==Epigenomic Alterations==

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The molecular mechanism is not completely understood, but the fusion protein is known to act as an aberrant transcription factor, alter nuclear transport and induce myeloid cell-specific global protein synthesis<ref name=":0" /><ref>{{Cite journal|last=Ageberg|first=Malin|last2=Drott|first2=Kristina|last3=Olofsson|first3=Tor|last4=Gullberg|first4=Urban|last5=Lindmark|first5=Anders|date=2008|title=Identification of a novel and myeloid specific role of the leukemia-associated fusion protein DEK-NUP214 leading to increased protein synthesis|url=https://www.ncbi.nlm.nih.gov/pubmed/18181180|journal=Genes, Chromosomes & Cancer|volume=47|issue=4|pages=276–287|doi=10.1002/gcc.20531|issn=1098-2264|pmid=18181180}}</ref>.

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==Genetic Diagnostic Testing Methods==