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

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

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Gordana Raca MD PhD, University of Southern California, Los Angeles

==WHO Classification of Disease==

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|Acceptable

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|Not Recommended

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==Gene Rearrangements==

Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Details on clinical significance such as prognosis and other important information can be provided in the notes section. Please include references throughout the table. Do not delete the table.'')</span>

* 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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|<span class="blue-text">EXAMPLE:</span>

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!Chromosomal Pattern

!Molecular Pathogenesis

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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" />.

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|<span class="blue-text">EXAMPLE:</span>''EGFR''

|}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>.  

(use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''Instructions: Add each reference into the text above by clicking where you want to insert the reference, selecting the “Cite” icon at the top of the wiki page, and using the “Automatic” tab option to search by PMID to select the reference to insert. If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference. To insert the same reference again later in the page, select the “Cite” icon and “Re-use” to find the reference; DO NOT insert the same reference twice using the “Automatic” tab as it will be treated as two separate references. The reference list in this section will be automatically generated and sorted''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">)</span> <references />

==Notes==

<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage).  Additional global feedback or concerns are also welcome.

<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>.