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

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

{{Under Construction}}

}}</blockquote>

==Primary Author(s)*==

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

{| class="wikitable"

|-

|}

{| class="wikitable sortable"

|-

|-

|-

|-

|-

|-

* Chromosomal Rearrangements (Gene Fusions)

* Individual Region Genomic Gain/Loss/LOH

* Characteristic Chromosomal Patterns

Diagnostic: The presence of inv(3)/t(3;3) defines a cytogenetic subtype of AML, however in the current WHO 2017 classification does not allow to make a diagnosis of AML if blast percentage <20%. Very poor prognosis and rapid progression of MDS with inv(3)(q21q26.2)/t(3;3)(q21;q26.2)  resulted in a proposal to consider neoplasms with these rearrangements as an AML  with recurrent genetic abnormalities, irrespective of blast percentage.

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>.

</blockquote>

{| class="wikitable sortable"

|-

|-

7

chr7

|-

8

chr8

|}

Put your text here.

</blockquote>

{| class="wikitable sortable"

|-

!Chromosomal Pattern

|-

Co-deletion of 1p and 18q

|}

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" />.

Deletion 5q

</blockquote>

{| class="wikitable sortable"

|-

|-

|

|

|

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.

|}

</blockquote>

==Epigenomic Alterations==

Put your text here

{| class="wikitable sortable"

|-

!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome

|-

|-

|-

|}

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>.  

Key cellular pathways: ''EVI1'' has been shown to be involved in multiple downstream signaling pathways, including the transforming growth factor beta (TGF-β) signaling (where ''EVI1'' prevents transcription of the TGF-β induced anti-growth genes ) and ''[[JUN|c-Jun N-terminal kinase]]'' (JNK) signaling (where ''EVI1'' prevents phosphorylation  and activation of key transcription factors for the apoptotic response).

</blockquote>

==Genetic Diagnostic Testing Methods==

==Familial Forms==

Put your text here <span style="color:#0070C0">(''Instructions: Include associated hereditary conditions/syndromes that cause this entity or are caused by this entity.'') </span>

==Additional Information==

==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>.