HAEM5:Adult T-cell leukaemia/lymphoma: Difference between revisions

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|Deletions, inversions, duplications, translocations at '''9p24.1''' disrupting 3′-UTR
|Deletions, inversions, duplications, translocations at '''9p24.1''' disrupting 3′-UTR
|Common (≈20–25% of ATLL in large cohorts)
|Common (≈20–25% of ATLL in large cohorts)
|
|T
|No
|No
|Highlights immune-evasion axis and immune checkpoint biology, but PD-1 blockade has shown harm and induced rapid progression in ATLL<ref>{{Cite journal|last=Rauch|first=Daniel A.|last2=Conlon|first2=Kevin C.|last3=Janakiram|first3=Murali|last4=Brammer|first4=Jonathan E.|last5=Harding|first5=John C.|last6=Ye|first6=B. Hilda|last7=Zang|first7=Xingxing|last8=Ren|first8=Xiaoxin|last9=Olson|first9=Sydney|date=2019-10-24|title=Rapid progression of adult T-cell leukemia/lymphoma as tumor-infiltrating Tregs after PD-1 blockade|url=https://pubmed.ncbi.nlm.nih.gov/31467059|journal=Blood|volume=134|issue=17|pages=1406–1414|doi=10.1182/blood.2019002038|issn=1528-0020|pmc=6839957|pmid=31467059}}</ref>
|Highlights immune-evasion axis and immune checkpoint biology, but PD-1 blockade has shown harm and induced rapid progression in ATLL<ref>{{Cite journal|last=Rauch|first=Daniel A.|last2=Conlon|first2=Kevin C.|last3=Janakiram|first3=Murali|last4=Brammer|first4=Jonathan E.|last5=Harding|first5=John C.|last6=Ye|first6=B. Hilda|last7=Zang|first7=Xingxing|last8=Ren|first8=Xiaoxin|last9=Olson|first9=Sydney|date=2019-10-24|title=Rapid progression of adult T-cell leukemia/lymphoma as tumor-infiltrating Tregs after PD-1 blockade|url=https://pubmed.ncbi.nlm.nih.gov/31467059|journal=Blood|volume=134|issue=17|pages=1406–1414|doi=10.1182/blood.2019002038|issn=1528-0020|pmc=6839957|pmid=31467059}}</ref>
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|Rearrangements within '''2q33''' region (CTLA4/ICOS/CD28 are clustered); interstitial events/inversions
|Rearrangements within '''2q33''' region (CTLA4/ICOS/CD28 are clustered); interstitial events/inversions
|Rare, but enriched in younger patients (3/8 cases, 37.5%<ref>{{Cite journal|last=Yoshida|first=Noriaki|last2=Shigemori|first2=Kay|last3=Donaldson|first3=Nicholas|last4=Trevisani|first4=Christopher|last5=Cordero|first5=Nicolas A.|last6=Stevenson|first6=Kristen E.|last7=Bu|first7=Xia|last8=Arakawa|first8=Fumiko|last9=Takeuchi|first9=Mai|date=2020-04-23|title=Genomic landscape of young ATLL patients identifies frequent targetable CD28 fusions|url=https://pubmed.ncbi.nlm.nih.gov/31961925|journal=Blood|volume=135|issue=17|pages=1467–1471|doi=10.1182/blood.2019001815|issn=1528-0020|pmc=7180081|pmid=31961925}}</ref>)
|Rare, but enriched in younger patients (3/8 cases, 37.5%<ref>{{Cite journal|last=Yoshida|first=Noriaki|last2=Shigemori|first2=Kay|last3=Donaldson|first3=Nicholas|last4=Trevisani|first4=Christopher|last5=Cordero|first5=Nicolas A.|last6=Stevenson|first6=Kristen E.|last7=Bu|first7=Xia|last8=Arakawa|first8=Fumiko|last9=Takeuchi|first9=Mai|date=2020-04-23|title=Genomic landscape of young ATLL patients identifies frequent targetable CD28 fusions|url=https://pubmed.ncbi.nlm.nih.gov/31961925|journal=Blood|volume=135|issue=17|pages=1467–1471|doi=10.1182/blood.2019001815|issn=1528-0020|pmc=7180081|pmid=31961925}}</ref>)
|
|T
|
|No
|Potential for CTLA4 blockade as treatment when CD28 fusions are present
|Potential for CTLA4 blockade as treatment when CD28 fusions are present
|-
|-
|''REL (c-Rel)''
|''REL (c-Rel)''
|3′ truncations (no partner gene; gain-of-function)
|3′ truncations (no partner gene; gain-of-function)
|Truncation removes negative-regulatory regions → REL upregulation/activation → NF-κB pathway activation
|C-terminal truncation removes negative-regulatory regions → transcription upregulation/activation of REL → NF-κB pathway activation
|'''2p16.1''' 3′-end truncating rearrangements
|'''2p16.1''' 3′-end truncating rearrangements
|Recurrent (~13%)
|Recurrent (~13%)
|
|
|
|No
|
|
|}
|}