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

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">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, p137-138.</ref>.

 

 

 

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" />.

|The t(6;9) is diagnostic of AML in the appropriate morphology and clinical context (add reference). ''DEK''::''NUP214'' has traditionally been associated with a poor prognosis in both adult and pediatric AML 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" />. Limited data suggests early allogeneic stem cell transplantation may be associated with better overall survival compared to patients without transplantation, suggesting accurate diagnosis for these patients is crucial<ref name=":0" /><ref>{{Cite journal|last=Slovak|first=M. L.|last2=Gundacker|first2=H.|last3=Bloomfield|first3=C. D.|last4=Dewald|first4=G.|last5=Appelbaum|first5=F. R.|last6=Larson|first6=R. A.|last7=Tallman|first7=M. S.|last8=Bennett|first8=J. M.|last9=Stirewalt|first9=D. L.|date=2006|title=A retrospective study of 69 patients with t(6;9)(p23;q34) AML emphasizes the need for a prospective, multicenter initiative for rare 'poor prognosis' myeloid malignancies|url=https://www.ncbi.nlm.nih.gov/pubmed/16628187|journal=Leukemia|volume=20|issue=7|pages=1295–1297|doi=10.1038/sj.leu.2404233|issn=0887-6924|pmid=16628187}}</ref><ref>{{Cite journal|last=Ishiyama|first=K.|last2=Takami|first2=A.|last3=Kanda|first3=Y.|last4=Nakao|first4=S.|last5=Hidaka|first5=M.|last6=Maeda|first6=T.|last7=Naoe|first7=T.|last8=Taniguchi|first8=S.|last9=Kawa|first9=K.|date=2012|title=Allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia with t(6;9)(p23;q34) dramatically improves the patient prognosis: a matched-pair analysis|url=https://www.ncbi.nlm.nih.gov/pubmed/21869835|journal=Leukemia|volume=26|issue=3|pages=461–464|doi=10.1038/leu.2011.229|issn=1476-5551|pmid=21869835}}</ref>.

|FLT3-ITD occurs in 69% of children and 78% of adults. In contrast to FLT3-ITD mutations, FLT3-TKD is very uncommon.