HAEM5:Acute myeloid leukaemia with RBM15::MRTFA fusion: Difference between revisions

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 |''RBM15'' and ''MKL1''
-|''RBM15''(''OTT'') / ''MKL1''(''MAL'')||The majority of both genes retained in the fusion 5’ ''DEK'' and 3’''NUP214''(''CAN'') with the pathogenic derivative being hte der(22).||t(1;22)(p13.3;q13.1)
+|''RBM15''(''OTT'')::''MKL1''(''MAL'')||The majority of both genes retained in the fusion 5’ ''DEK'' and 3’''NUP214''(''CAN'') with the pathogenic derivative being hte der(22).||t(1;22)(p13.3;q13.1)
 |Rare (AML)
 |D
 |Yes (WHO)
 |
-*This AML subtype is classified based on the presence by karyotype of a t(1;22)(p13.3;q13.1) or molecular confirmation of fusion of ''RBM15''(''OTT'') at 1p13.3 [hg38] and ''MKL1''(''MAL'') at 22q13.1 [hg38] with variable breakpoints<ref name=":1">{{Cite journal|last=Ma|first=Z.|last2=Morris|first2=S. W.|last3=Valentine|first3=V.|last4=Li|first4=M.|last5=Herbrick|first5=J. A.|last6=Cui|first6=X.|last7=Bouman|first7=D.|last8=Li|first8=Y.|last9=Mehta|first9=P. K.|date=2001|title=Fusion of two novel genes, RBM15 and MKL1, in the t(1;22)(p13;q13) of acute megakaryoblastic leukemia|url=https://www.ncbi.nlm.nih.gov/pubmed/11431691|journal=Nature Genetics|volume=28|issue=3|pages=220–221|doi=10.1038/90054|issn=1061-4036|pmid=11431691}}</ref><ref name=":3">WHO Classification of Tumours Editorial Board, eds, WHO Classification of Tumours, Haematolymphoid Tumours, 5th edition, IARC Press:Lyon, 2024.  Online at: [https://tumourclassification.iarc.who.int/welcome/ WHO Classification of Tumours].</ref><ref>{{Cite journal|last=Khoury|first=Joseph D.|last2=Solary|first2=Eric|last3=Abla|first3=Oussama|last4=Akkari|first4=Yassmine|last5=Alaggio|first5=Rita|last6=Apperley|first6=Jane F.|last7=Bejar|first7=Rafael|last8=Berti|first8=Emilio|last9=Busque|first9=Lambert|date=2022-07|title=The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms|url=https://pubmed.ncbi.nlm.nih.gov/35732831|journal=Leukemia|volume=36|issue=7|pages=1703–1719|doi=10.1038/s41375-022-01613-1|issn=1476-5551|pmc=9252913|pmid=35732831}}</ref>.  Although both reciprocal fusions are expressed, the in-frame ''RBM15''-''MKL1'' fusion on the derivative chromosome 22 is the candidate oncoprotein because it contains all of the putative functional domains of both proteins<ref name=":1" />.
+*This AML subtype is classified based on the presence by karyotype of a t(1;22)(p13.3;q13.1) or molecular confirmation of fusion of ''RBM15''(''OTT'') at 1p13.3 [hg38] and ''MKL1''(''MAL'') at 22q13.1 [hg38] with variable breakpoints<ref name=":1">{{Cite journal|last=Ma|first=Z.|last2=Morris|first2=S. W.|last3=Valentine|first3=V.|last4=Li|first4=M.|last5=Herbrick|first5=J. A.|last6=Cui|first6=X.|last7=Bouman|first7=D.|last8=Li|first8=Y.|last9=Mehta|first9=P. K.|date=2001|title=Fusion of two novel genes, RBM15 and MKL1, in the t(1;22)(p13;q13) of acute megakaryoblastic leukemia|url=https://www.ncbi.nlm.nih.gov/pubmed/11431691|journal=Nature Genetics|volume=28|issue=3|pages=220–221|doi=10.1038/90054|issn=1061-4036|pmid=11431691}}</ref><ref name=":3">WHO Classification of Tumours Editorial Board, eds, WHO Classification of Tumours, Haematolymphoid Tumours, 5th edition, IARC Press:Lyon, 2024.  Online at: [https://tumourclassification.iarc.who.int/welcome/ WHO Classification of Tumours].</ref><ref>{{Cite journal|last=Khoury|first=Joseph D.|last2=Solary|first2=Eric|last3=Abla|first3=Oussama|last4=Akkari|first4=Yassmine|last5=Alaggio|first5=Rita|last6=Apperley|first6=Jane F.|last7=Bejar|first7=Rafael|last8=Berti|first8=Emilio|last9=Busque|first9=Lambert|date=2022-07|title=The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms|url=https://pubmed.ncbi.nlm.nih.gov/35732831|journal=Leukemia|volume=36|issue=7|pages=1703–1719|doi=10.1038/s41375-022-01613-1|issn=1476-5551|pmc=9252913|pmid=35732831}}</ref>.  Although both reciprocal fusions are expressed, the in-frame ''RBM15''::''MKL1'' fusion on the derivative chromosome 22 is the candidate oncoprotein because it contains all of the putative functional domains of both proteins<ref name=":1" />.
-*Typically the ''RBM15''-''MKL1'' fusion presents as the sole abnormality<ref name=":3" />.
+*The ''RBM15''::''MKL1'' fusion typically presents as the sole abnormality<ref name=":3" />. A hyperdiploid karyotype with t(1;22) and +der(1)t(1;22) can be observed less frequently, typically in infants aged >6 months<ref>{{Cite journal|last=Carroll|first=A.|last2=Civin|first2=C.|last3=Schneider|first3=N.|last4=Dahl|first4=G.|last5=Pappo|first5=A.|last6=Bowman|first6=P.|last7=Emami|first7=A.|last8=Gross|first8=S.|last9=Alvarado|first9=C.|date=1991-08-01|title=The t(1;22) (p13;q13) is nonrandom and restricted to infants with acute megakaryoblastic leukemia: a Pediatric Oncology Group Study|url=https://pubmed.ncbi.nlm.nih.gov/1859887|journal=Blood|volume=78|issue=3|pages=748–752|issn=0006-4971|pmid=1859887}}</ref>. Pediatric non-Down syndrome AMKL can arise through other genetic mechanisms that are unrelated to
 *The t(1;22) occurs in <1% of all AML cases and 10-12% of pediatric acute megakaryoblastic leukemia cases<ref name=":4" />. It is most frequent in infants (<6 months old) and young children (<3 years old) with Down syndrome and has a female predominance. Rarely it occurs in adults<ref>{{Cite journal|last=Hsiao|first=Hui-Hua|last2=Yang|first2=Ming-Yu|last3=Liu|first3=Yi-Chang|last4=Hsiao|first4=Hui-Pin|last5=Tseng|first5=Shih-Bin|last6=Chao|first6=Mei-Chyn|last7=Liu|first7=Ta-Chih|last8=Lin|first8=Sheng-Fung|date=2005-05|title=RBM15-MKL1 (OTT-MAL) fusion transcript in an adult acute myeloid leukemia patient|url=https://pubmed.ncbi.nlm.nih.gov/15849773|journal=American Journal of Hematology|volume=79|issue=1|pages=43–45|doi=10.1002/ajh.20298|issn=0361-8609|pmid=15849773}}</ref><ref>{{Cite journal|last=Saito|first=Yo|last2=Makita|first2=Shinichi|last3=Chinen|first3=Shotaro|last4=Kito|first4=Momoko|last5=Fujino|first5=Takahiro|last6=Ida|first6=Hanae|last7=Hosoba|first7=Rika|last8=Tanaka|first8=Takashi|last9=Fukuhara|first9=Suguru|date=2020-09|title=Acute megakaryoblastic leukaemia with t(1;22)(p13·3;q13·1)/RBM15-MKL1 in an adult patient following a non-mediastinal germ cell tumour|url=https://pubmed.ncbi.nlm.nih.gov/32572949|journal=British Journal of Haematology|volume=190|issue=6|pages=e329–e332|doi=10.1111/bjh.16900|issn=1365-2141|pmid=32572949}}</ref>.