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

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|''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)

!Chr #!!'''Gain, Loss, Amp, LOH'''!!'''Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size]'''!!'''Relevant Gene(s)'''

!'''Diagnostic, Prognostic, and Therapeutic Significance - D, P, T'''

!'''Established Clinical Significance Per Guidelines - Yes or No (Source)'''

!'''Clinical Relevance Details/Other Notes'''

!'''Prevalence -'''

'''Common >20%, Recurrent 5-20% or Rare <5% (Disease)'''

!'''Diagnostic, Prognostic, and Therapeutic Significance - D, P, T'''

!'''Established Clinical Significance Per Guidelines - Yes or No (Source)'''

!'''Clinical Relevance Details/Other Notes'''

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

!Gene!!'''Genetic Alteration'''!!'''Tumor Suppressor Gene, Oncogene, Other'''!!'''Prevalence -'''

'''Common >20%, Recurrent 5-20% or Rare <5% (Disease)'''

!'''Diagnostic, Prognostic, and Therapeutic Significance - D, P, T  '''

!'''Established Clinical Significance Per Guidelines - Yes or No (Source)'''

!'''Clinical Relevance Details/Other Notes'''

The molecular mechanism is not completely understood, but the fusion protein may modulate chromatin organization, HOX-induced differentiation and extracellular signaling pathways associated with leukemogenesis<ref>{{Cite journal|last=Mercher|first=T.|last2=Coniat|first2=M. B.|last3=Monni|first3=R.|last4=Mauchauffe|first4=M.|last5=Nguyen Khac|first5=F.|last6=Gressin|first6=L.|last7=Mugneret|first7=F.|last8=Leblanc|first8=T.|last9=Dastugue|first9=N.|date=2001-05-08|title=Involvement of a human gene related to the Drosophila spen gene in the recurrent t(1;22) translocation of acute megakaryocytic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/11344311|journal=Proceedings of the National Academy of Sciences of the United States of America|volume=98|issue=10|pages=5776–5779|doi=10.1073/pnas.101001498|issn=0027-8424|pmc=33289|pmid=11344311}}</ref>.  The fusion of MKL1 to RBM15 deregulates the normal intracellular localization of MKL1 such that it is becomes constitutively localized to the nucleus, resulting in serum response factor (SRF) activation even in the absence of stimuli<ref>{{Cite journal|last=Gruber|first=Tanja A.|last2=Downing|first2=James R.|date=2015-08-20|title=The biology of pediatric acute megakaryoblastic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/26186939|journal=Blood|volume=126|issue=8|pages=943–949|doi=10.1182/blood-2015-05-567859|issn=1528-0020|pmc=4551356|pmid=26186939}}</ref>. SRF is a transcription factor that regulates the expression of genes involved in cell growth, proliferation, and differentiation, as well as genes that control the actin cytoskeleton<ref>{{Cite journal|last=Halene|first=Stephanie|last2=Gao|first2=Yuan|last3=Hahn|first3=Katherine|last4=Massaro|first4=Stephanie|last5=Italiano|first5=Joseph E.|last6=Schulz|first6=Vincent|last7=Lin|first7=Sharon|last8=Kupfer|first8=Gary M.|last9=Krause|first9=Diane S.|date=2010-09-16|title=Serum response factor is an essential transcription factor in megakaryocytic maturation|url=https://pubmed.ncbi.nlm.nih.gov/20525922|journal=Blood|volume=116|issue=11|pages=1942–1950|doi=10.1182/blood-2010-01-261743|issn=1528-0020|pmc=3173990|pmid=20525922}}</ref>. Of note, while a ''RBM15''::''MKL1'' fusion knock-in model mouse shoed abnormal megakaryopoiesis, it was not sufficient to induce leukemia<ref>{{Cite journal|last=Mercher|first=Thomas|last2=Raffel|first2=Glen D.|last3=Moore|first3=Sandra A.|last4=Cornejo|first4=Melanie G.|last5=Baudry-Bluteau|first5=Dominique|last6=Cagnard|first6=Nicolas|last7=Jesneck|first7=Jonathan L.|last8=Pikman|first8=Yana|last9=Cullen|first9=Dana|date=2009-04|title=The OTT-MAL fusion oncogene activates RBPJ-mediated transcription and induces acute megakaryoblastic leukemia in a knockin mouse model|url=https://pubmed.ncbi.nlm.nih.gov/19287095|journal=The Journal of Clinical Investigation|volume=119|issue=4|pages=852–864|doi=10.1172/JCI35901|issn=1558-8238|pmc=2662544|pmid=19287095}}</ref>.

|HOX signaling

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Karyotype, FISH, RT-PCR

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