HAEM5:Acute myeloid leukaemia with MECOM rearrangement: Difference between revisions

{{DISPLAYTITLE:Acute myeloid leukaemia with MECOM rearrangement}}

[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (WHO Classification, 5th ed.)]]

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|Subtype(s)

|Acute myeloid leukaemia with MECOM rearrangement

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* Chromosomal Rearrangements (Gene Fusions)

* Individual Region Genomic Gain/Loss/LOH

BCR-ABL1 positive patients with CML and concomitant MECOM rearrangement are considered in an aggressive phase of CML (Accelerated Phase) rather than de novo AML with inv(3)/t(3;3)

Therapeutic: AML with inv(3)(q21q26.2) or t(3;3) (q21;q26.2) is an aggressive disease with short survival, in need for novel and more efficient treatments. Some studies have shown that arsenic trioxide induces targeted specific degradation of the AML1/MDS1/EVI1 oncoprotein, and an isolated case report described  good response to Arsenic trioxide and thalidomide combination in a patient with MDS with inv(3)<ref>{{Cite journal|last=Shackelford|first=David|last2=Kenific|first2=Candia|last3=Blusztajn|first3=Agnieszka|last4=Waxman|first4=Samuel|last5=Ren|first5=Ruibao|date=2006|title=Targeted degradation of the AML1/MDS1/EVI1 oncoprotein by arsenic trioxide|url=https://www.ncbi.nlm.nih.gov/pubmed/17145882|journal=Cancer Research|volume=66|issue=23|pages=11360–11369|doi=10.1158/0008-5472.CAN-06-1774|issn=0008-5472|pmid=17145882}}</ref><ref>{{Cite journal|last=Raza|first=Azra|last2=Buonamici|first2=Silvia|last3=Lisak|first3=Laurie|last4=Tahir|first4=Sarah|last5=Li|first5=Donglan|last6=Imran|first6=Mehnaz|last7=Chaudary|first7=Nusrat Ijaz|last8=Pervaiz|first8=Hassan|last9=Gallegos|first9=J. Alejandro|date=2004|title=Arsenic trioxide and thalidomide combination produces multi-lineage hematological responses in myelodysplastic syndromes patients, particularly in those with high pre-therapy EVI1 expression|url=https://www.ncbi.nlm.nih.gov/pubmed/15203277|journal=Leukemia Research|volume=28|issue=8|pages=791–803|doi=10.1016/j.leukres.2003.11.018|issn=0145-2126|pmid=15203277}}</ref>.

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Monosomy 7 is the most common associated (secondary) cytogenetic abnormality (in ~66% of cases), and appears to further contribute to the adverse prognosis of the inv(3q)/t(3;3) abnormality<ref name=":0" /><ref name=":1" />.

|}Note: A more extensive list of mutations can be found in [https://www.cbioportal.org/ <u>cBioportal</u>], [https://cancer.sanger.ac.uk/cosmic <u>COSMIC</u>], and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.

Secondary mutations are found in all AML cases with inv(3) ot t(3;3). Mutations in genes activating RAS/TK signaling pathway are the most common mutation.

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The ''[[MECOM]]'' (MDS1 and EVI1 complex locus)  gene in 3q26.3 is the key gene implicated in pathogenesis of AML with inv(3)/t(3;3). ''MECOM'' codes for several differentially spliced transcripts: MDS1-EVI1, MDS1 and EVI1. It consequently yields the MDS1-EVI1 [1239 amino acids (AA)], MDS1 (188AA) and EVI1 (1051AA) protein isoforms. While ''EVI1'' deregulated expression has been reported to be critical in stem cell self-renewal and leukaemogenesis, the roles of ''MDS1'' and MDS1-EVI1 in haematological malignancies remain unclear<ref name=":2">{{Cite journal|last=Wieser|first=Rotraud|date=2007|title=The oncogene and developmental regulator EVI1: expression, biochemical properties, and biological functions|url=https://www.ncbi.nlm.nih.gov/pubmed/17507183|journal=Gene|volume=396|issue=2|pages=346–357|doi=10.1016/j.gene.2007.04.012|issn=0378-1119|pmid=17507183}}</ref>.  

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==Notes==

<nowiki>*</nowiki>''Citation of this Page'': “Acute myeloid leukaemia with MECOM rearrangement”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Acute_myeloid_leukaemia_with_MECOM_rearrangement</nowiki>.