Compendium of Cancer Genome Aberrations

HAEM5:B lymphoblastic leukaemia/lymphoma with TCF3::PBX1 fusion: Difference between revisions

(View all pending changes)
[pending revision][pending revision]
← Older edit
VisualWikitext
Tags: Manual revert Visual edit
 
(3 intermediate revisions by the same user not shown)
Line 58: Line 58:
|-
|-
|''TCF3::PBX1'' fusion protein||''TCF3::PBX1''||The ''TCF3''::''PBX1'' fusion results in the production of a fusion protein that has an oncogenic role as a transcriptional activator; it also probably interferes with the normal function of the transcription factors encoded by ''TCF3'' and ''PBX1''<ref>{{Cite journal|last=LeBrun|first=David P.|date=2003-05-01|title=E2A basic helix-loop-helix transcription factors in human leukemia|url=https://pubmed.ncbi.nlm.nih.gov/12700034|journal=Frontiers in Bioscience: A Journal and Virtual Library|volume=8|pages=s206–222|doi=10.2741/1030|issn=1093-9946|pmid=12700034}}</ref>. Oligomerization and/or direct interaction with HOX proteins through the PBX1 moiety may play a role in ''TCF3-PBX1'' leukemogenesis<ref>{{Cite journal|last=Lin|first=Chiou-Hong|last2=Wang|first2=Zhong|last3=Duque-Afonso|first3=Jesús|last4=Wong|first4=Stephen Hon-Kit|last5=Demeter|first5=Janos|last6=Loktev|first6=Alexander V.|last7=Somervaille|first7=Tim C. P.|last8=Jackson|first8=Peter K.|last9=Cleary|first9=Michael L.|date=2019-03-20|title=Oligomeric self-association contributes to E2A-PBX1-mediated oncogenesis|url=https://pubmed.ncbi.nlm.nih.gov/30894657|journal=Scientific Reports|volume=9|issue=1|pages=4915|doi=10.1038/s41598-019-41393-w|issn=2045-2322|pmc=6426973|pmid=30894657}}</ref>.||t(1;19)(q23;q13.3)
|''TCF3::PBX1'' fusion protein||''TCF3::PBX1''||The ''TCF3''::''PBX1'' fusion results in the production of a fusion protein that has an oncogenic role as a transcriptional activator; it also probably interferes with the normal function of the transcription factors encoded by ''TCF3'' and ''PBX1''<ref>{{Cite journal|last=LeBrun|first=David P.|date=2003-05-01|title=E2A basic helix-loop-helix transcription factors in human leukemia|url=https://pubmed.ncbi.nlm.nih.gov/12700034|journal=Frontiers in Bioscience: A Journal and Virtual Library|volume=8|pages=s206–222|doi=10.2741/1030|issn=1093-9946|pmid=12700034}}</ref>. Oligomerization and/or direct interaction with HOX proteins through the PBX1 moiety may play a role in ''TCF3-PBX1'' leukemogenesis<ref>{{Cite journal|last=Lin|first=Chiou-Hong|last2=Wang|first2=Zhong|last3=Duque-Afonso|first3=Jesús|last4=Wong|first4=Stephen Hon-Kit|last5=Demeter|first5=Janos|last6=Loktev|first6=Alexander V.|last7=Somervaille|first7=Tim C. P.|last8=Jackson|first8=Peter K.|last9=Cleary|first9=Michael L.|date=2019-03-20|title=Oligomeric self-association contributes to E2A-PBX1-mediated oncogenesis|url=https://pubmed.ncbi.nlm.nih.gov/30894657|journal=Scientific Reports|volume=9|issue=1|pages=4915|doi=10.1038/s41598-019-41393-w|issn=2045-2322|pmc=6426973|pmid=30894657}}</ref>.||t(1;19)(q23;q13.3)
|Common
|Ubiquitous
|D: Requires demonstration of ''TCF3''::''PBX1'' rearrangement
|D: Requires demonstration of ''TCF3''::''PBX1'' rearrangement
P: Associated with intermediate to relatively favorable clinical outcomes<ref>{{Cite journal|last=Burmeister|first=Thomas|last2=Gökbuget|first2=Nicola|last3=Schwartz|first3=Stefan|last4=Fischer|first4=Lars|last5=Hubert|first5=Daniela|last6=Sindram|first6=Annette|last7=Hoelzer|first7=Dieter|last8=Thiel|first8=Eckhard|date=2010-02|title=Clinical features and prognostic implications of TCF3-PBX1 and ETV6-RUNX1 in adult acute lymphoblastic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/19713226|journal=Haematologica|volume=95|issue=2|pages=241–246|doi=10.3324/haematol.2009.011346|issn=1592-8721|pmc=2817026|pmid=19713226}}</ref><ref>{{Cite journal|last=Felice|first=María S.|last2=Gallego|first2=Marta S.|last3=Alonso|first3=Cristina N.|last4=Alfaro|first4=Elizabeth M.|last5=Guitter|first5=Myriam R.|last6=Bernasconi|first6=Andrea R.|last7=Rubio|first7=Patricia L.|last8=Zubizarreta|first8=Pedro A.|last9=Rossi|first9=Jorge G.|date=2011-07|title=Prognostic impact of t(1;19)/ TCF3-PBX1 in childhood acute lymphoblastic leukemia in the context of Berlin-Frankfurt-Münster-based protocols|url=https://pubmed.ncbi.nlm.nih.gov/21534874|journal=Leukemia & Lymphoma|volume=52|issue=7|pages=1215–1221|doi=10.3109/10428194.2011.565436|issn=1029-2403|pmid=21534874}}</ref><ref>{{Cite journal|last=Lin|first=Anna|last2=Cheng|first2=Frankie W. T.|last3=Chiang|first3=Alan K. S.|last4=Luk|first4=Chung-Wing|last5=Li|first5=Rever C. H.|last6=Ling|first6=Alvin S. C.|last7=Cheuk|first7=Daniel K. L.|last8=Chang|first8=Kai-On|last9=Ku|first9=Dennis|date=2018-12|title=Excellent outcome of acute lymphoblastic leukaemia with TCF3-PBX1 rearrangement in Hong Kong|url=https://pubmed.ncbi.nlm.nih.gov/30051646|journal=Pediatric Blood & Cancer|volume=65|issue=12|pages=e27346|doi=10.1002/pbc.27346|issn=1545-5017|pmid=30051646}}</ref><ref>{{Cite journal|last=Yilmaz|first=Musa|last2=Kantarjian|first2=Hagop M.|last3=Toruner|first3=Gokce|last4=Yin|first4=C. Cameron|last5=Kanagal-Shamanna|first5=Rashmi|last6=Cortes|first6=Jorge E.|last7=Issa|first7=Ghayyas|last8=Short|first8=Nicholas J.|last9=Khoury|first9=Joseph D.|date=2021-01|title=Translocation t(1;19)(q23;p13) in adult acute lymphoblastic leukemia - a distinct subtype with favorable prognosis|url=https://pubmed.ncbi.nlm.nih.gov/32955970|journal=Leukemia & Lymphoma|volume=62|issue=1|pages=224–228|doi=10.1080/10428194.2020.1824071|issn=1029-2403|pmc=11648456|pmid=32955970}}</ref>
P: Associated with intermediate to relatively favorable clinical outcomes<ref>{{Cite journal|last=Burmeister|first=Thomas|last2=Gökbuget|first2=Nicola|last3=Schwartz|first3=Stefan|last4=Fischer|first4=Lars|last5=Hubert|first5=Daniela|last6=Sindram|first6=Annette|last7=Hoelzer|first7=Dieter|last8=Thiel|first8=Eckhard|date=2010-02|title=Clinical features and prognostic implications of TCF3-PBX1 and ETV6-RUNX1 in adult acute lymphoblastic leukemia|url=https://pubmed.ncbi.nlm.nih.gov/19713226|journal=Haematologica|volume=95|issue=2|pages=241–246|doi=10.3324/haematol.2009.011346|issn=1592-8721|pmc=2817026|pmid=19713226}}</ref><ref>{{Cite journal|last=Felice|first=María S.|last2=Gallego|first2=Marta S.|last3=Alonso|first3=Cristina N.|last4=Alfaro|first4=Elizabeth M.|last5=Guitter|first5=Myriam R.|last6=Bernasconi|first6=Andrea R.|last7=Rubio|first7=Patricia L.|last8=Zubizarreta|first8=Pedro A.|last9=Rossi|first9=Jorge G.|date=2011-07|title=Prognostic impact of t(1;19)/ TCF3-PBX1 in childhood acute lymphoblastic leukemia in the context of Berlin-Frankfurt-Münster-based protocols|url=https://pubmed.ncbi.nlm.nih.gov/21534874|journal=Leukemia & Lymphoma|volume=52|issue=7|pages=1215–1221|doi=10.3109/10428194.2011.565436|issn=1029-2403|pmid=21534874}}</ref><ref>{{Cite journal|last=Lin|first=Anna|last2=Cheng|first2=Frankie W. T.|last3=Chiang|first3=Alan K. S.|last4=Luk|first4=Chung-Wing|last5=Li|first5=Rever C. H.|last6=Ling|first6=Alvin S. C.|last7=Cheuk|first7=Daniel K. L.|last8=Chang|first8=Kai-On|last9=Ku|first9=Dennis|date=2018-12|title=Excellent outcome of acute lymphoblastic leukaemia with TCF3-PBX1 rearrangement in Hong Kong|url=https://pubmed.ncbi.nlm.nih.gov/30051646|journal=Pediatric Blood & Cancer|volume=65|issue=12|pages=e27346|doi=10.1002/pbc.27346|issn=1545-5017|pmid=30051646}}</ref><ref>{{Cite journal|last=Yilmaz|first=Musa|last2=Kantarjian|first2=Hagop M.|last3=Toruner|first3=Gokce|last4=Yin|first4=C. Cameron|last5=Kanagal-Shamanna|first5=Rashmi|last6=Cortes|first6=Jorge E.|last7=Issa|first7=Ghayyas|last8=Short|first8=Nicholas J.|last9=Khoury|first9=Joseph D.|date=2021-01|title=Translocation t(1;19)(q23;p13) in adult acute lymphoblastic leukemia - a distinct subtype with favorable prognosis|url=https://pubmed.ncbi.nlm.nih.gov/32955970|journal=Leukemia & Lymphoma|volume=62|issue=1|pages=224–228|doi=10.1080/10428194.2020.1824071|issn=1029-2403|pmc=11648456|pmid=32955970}}</ref>. 5-year event-free survival (80-88.2%)<ref>{{Cite journal|last=Jeha|first=Sima|last2=Choi|first2=John|last3=Roberts|first3=Kathryn G.|last4=Pei|first4=Deqing|last5=Coustan-Smith|first5=Elaine|last6=Inaba|first6=Hiroto|last7=Rubnitz|first7=Jeffrey E.|last8=Ribeiro|first8=Raul C.|last9=Gruber|first9=Tanja A.|date=2021-07|title=Clinical significance of novel subtypes of acute lymphoblastic leukemia in the context of minimal residual disease-directed therapy|url=https://pubmed.ncbi.nlm.nih.gov/34250504|journal=Blood Cancer Discovery|volume=2|issue=4|pages=326–337|doi=10.1158/2643-3230.bcd-20-0229|issn=2643-3249|pmc=8265990|pmid=34250504}}</ref>.


T: N/A
T: N/A
Line 83: Line 83:
<blockquote class="blockedit">
<blockquote class="blockedit">
<center><span style="color:Maroon">'''End of V4 Section'''</span>
<center>
----
</blockquote>
</blockquote>
 
<blockquote class="blockedit"></blockquote>
 
<blockquote class="blockedit">{{Box-round|title=v4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).|Please incorporate this section into the relevant tables found in:
* Chromosomal Rearrangements (Gene Fusions)
* Individual Region Genomic Gain/Loss/LOH
* Characteristic Chromosomal Patterns
* Gene Mutations (SNV/INDEL)}}</blockquote>
 
The t(1;19) diagnosis was associated with high risk and poor prognosis in earlier studies, however, modern intensive chemotherapy has changed this paradigm. A recent (2021) study showed that patients with ''TCF3-PBX1'' had intermediate rates of 5-year event-free survival (80-88.2%). Despite the favorable prognosis of this subtype of ALL, there is an increased relative risk of central nervous system relapse associated with this translocation.  <ref name=":1">Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J (Eds): WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (Revised 4th edition). IARC: Lyon 2017</ref><ref name=":0" /><ref>{{Cite journal|last=Jeha|first=Sima|last2=Choi|first2=John|last3=Roberts|first3=Kathryn G.|last4=Pei|first4=Deqing|last5=Coustan-Smith|first5=Elaine|last6=Inaba|first6=Hiroto|last7=Rubnitz|first7=Jeffrey E.|last8=Ribeiro|first8=Raul C.|last9=Gruber|first9=Tanja A.|date=2021-07|title=Clinical significance of novel subtypes of acute lymphoblastic leukemia in the context of minimal residual disease-directed therapy|url=https://pubmed.ncbi.nlm.nih.gov/34250504|journal=Blood Cancer Discovery|volume=2|issue=4|pages=326–337|doi=10.1158/2643-3230.bcd-20-0229|issn=2643-3249|pmc=8265990|pmid=34250504}}</ref>


<blockquote class="blockedit">
<blockquote class="blockedit">
<center><span style="color:Maroon">'''End of V4 Section'''</span>
<center>
----
----
</blockquote>
</blockquote>
==Individual Region Genomic Gain/Loss/LOH==
==Individual Region Genomic Gain/Loss/LOH==


Secondary somatic copy number aberrations are not frequently seen in ''TCF3-PBX1'' B-ALL.
Secondary somatic copy number aberrations are not frequently seen in ''TCF3-PBX1'' B-ALL<ref>WHO Classification of Tumours: Haematolymphoid Tumours [Internet; Beta Version Ahead of Print](5th ed.), International Agency for Research on Cancer (2022)</ref>.
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene rearrangements. Details on clinical significance such as prognosis and other important information can be provided in the notes section. Can refer to CGC workgroup tables as linked on the homepage if applicable. Please include references throughout the table. Do not delete the table.'') </span>
{| class="wikitable sortable"
{| class="wikitable sortable"
|-
|-
Line 156: Line 146:
|}
|}


<blockquote class="blockedit">{{Box-round|title=v4:Genomic Gain/Loss/LOH|The content below was from the old template. Please incorporate above.}}</blockquote>
<blockquote class="blockedit"></blockquote><blockquote class="blockedit">
 
<center>
Secondary somatic copy number aberrations are not frequently seen in ''TCF3-PBX1'' B-ALL
<blockquote class="blockedit">
<center><span style="color:Maroon">'''End of V4 Section'''</span>
----
----
</blockquote>
</blockquote>
Line 278: Line 265:
<blockquote class="blockedit">{{Box-round|title=v4:Genes and Main Pathways Involved|The content below was from the old template. Please incorporate above.}}</blockquote>
<blockquote class="blockedit">{{Box-round|title=v4:Genes and Main Pathways Involved|The content below was from the old template. Please incorporate above.}}</blockquote>


''TCF3'' gene at 19p13.3 is important during early lymphocyte development, whereas ''PBX1'' at 1q23 is a component of a transcriptional complex that regulates embryogenesis and hematopoiesis. Fusion protein resulting from the TCF3-PBX1 translocation is a transcriptional activator which likely interferes with the normal function of these genes. Expression of this fusion protein is thought to interfere with key regulatory pathways such as WNT and apoptosis/cell cycle control pathways which may drive a leukemic process. The DNA-binding and protein dimerization domains of PBX1 replaces the TCF3 helix-loop-helix DNA-binding motif in ''TCF3-PBX1'' fusion. The remaining transcriptional activating domains of TCF3 leads to constitutive nuclear localization and transformation of PBX1 into an oncogenic transcriptional factor <ref>{{Cite journal|last=Diakos|first=Christofer|last2=Xiao|first2=Yuanyuan|last3=Zheng|first3=Shichun|last4=Kager|first4=Leo|last5=Dworzak|first5=Michael|last6=Wiemels|first6=Joseph L.|date=2014|title=Direct and indirect targets of the E2A-PBX1 leukemia-specific fusion protein|url=https://pubmed.ncbi.nlm.nih.gov/24503810|journal=PloS One|volume=9|issue=2|pages=e87602|doi=10.1371/journal.pone.0087602|issn=1932-6203|pmc=3913655|pmid=24503810}}</ref><ref name=":1" /><ref name=":0" />
''TCF3'' gene at 19p13.3 is important during early lymphocyte development, whereas ''PBX1'' at 1q23 is a component of a transcriptional complex that regulates embryogenesis and hematopoiesis. Fusion protein resulting from the TCF3-PBX1 translocation is a transcriptional activator which likely interferes with the normal function of these genes. Expression of this fusion protein is thought to interfere with key regulatory pathways such as WNT and apoptosis/cell cycle control pathways which may drive a leukemic process. The DNA-binding and protein dimerization domains of PBX1 replaces the TCF3 helix-loop-helix DNA-binding motif in ''TCF3-PBX1'' fusion. The remaining transcriptional activating domains of TCF3 leads to constitutive nuclear localization and transformation of PBX1 into an oncogenic transcriptional factor <ref>{{Cite journal|last=Diakos|first=Christofer|last2=Xiao|first2=Yuanyuan|last3=Zheng|first3=Shichun|last4=Kager|first4=Leo|last5=Dworzak|first5=Michael|last6=Wiemels|first6=Joseph L.|date=2014|title=Direct and indirect targets of the E2A-PBX1 leukemia-specific fusion protein|url=https://pubmed.ncbi.nlm.nih.gov/24503810|journal=PloS One|volume=9|issue=2|pages=e87602|doi=10.1371/journal.pone.0087602|issn=1932-6203|pmc=3913655|pmid=24503810}}</ref><ref name=":1">Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J (Eds): WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (Revised 4th edition). IARC: Lyon 2017</ref><ref name=":0" />


<blockquote class="blockedit">
<blockquote class="blockedit">
Retrieved from "https://test.ccga.io/index.php/HAEM5:B_lymphoblastic_leukaemia/lymphoma_with_TCF3::PBX1_fusion"