B lymphoblastic leukaemia/lymphoma with TCF3::PBX1 fusion
Haematolymphoid Tumours (WHO Classification, 5th ed.)
Primary Author(s)*
Miguel Gonzalez Mancera, MD
WHO Classification of Disease
| Structure | Disease |
|---|---|
| Book | Haematolymphoid Tumours (5th ed.) |
| Category | B-cell lymphoid proliferations and lymphomas |
| Family | Precursor B-cell neoplasms |
| Type | B-lymphoblastic leukaemias/lymphomas |
| Subtype(s) | B lymphoblastic leukaemia/lymphoma with TCF3::PBX1 fusion |
Related Terminology
| Acceptable | N/A |
| Not Recommended | B-lymphoblastic leukaemia/lymphoma with E2A::PBX1 |
Gene Rearrangements
| Driver Gene | Fusion(s) and Common Partner Genes | Molecular Pathogenesis | Typical Chromosomal Alteration(s) | Prevalence -Common >20%, Recurrent 5-20% or Rare <5% (Disease) | Diagnostic, Prognostic, and Therapeutic Significance - D, P, T | Established Clinical Significance Per Guidelines - Yes or No (Source) | Clinical Relevance Details/Other Notes |
|---|---|---|---|---|---|---|---|
| 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[1]. Oligomerization and/or direct interaction with HOX proteins through the PBX1 moiety may play a role in TCF3-PBX1 leukemogenesis[2]. | t(1;19)(q23;q13.3) | Ubiquitous | D: Requires demonstration of TCF3::PBX1 rearrangement
P: Associated with intermediate to relatively favorable clinical outcomes[3][4][5][6]. 5-year event-free survival (80-88.2%)[7]. T: N/A |
No (NCCN) | There may be an increased relative risk of CNS relapse in these patients[8]. Relapsed patients appear to have a dismal prognosis.
Although the t(1;19) translocation can be readily detected by conventional chromosome studies, FISH confirmation is often needed since a karyotypically similar t(1;19) without involvement of TCF3 or PBX1 has been reported[9]. |
The breakpoints of the t(1;19) translocation typically fall within intron 16 of TCF3 and intron 3 of PBX1. [9]
Individual Region Genomic Gain/Loss/LOH
| Chr # | Gain, Loss, Amp, LOH | Minimal Region Cytoband and/or Genomic Coordinates [Genome Build; Size] | Relevant Gene(s) | Diagnostic, Prognostic, and Therapeutic Significance - D, P, T | Established Clinical Significance Per Guidelines - Yes or No (Source) | Clinical Relevance Details/Other Notes |
|---|---|---|---|---|---|---|
| dup(1q) | ||||||
| del(6q) | ||||||
| +8 | ||||||
| i(9q) | ||||||
| i(17q) | ||||||
| +21 |
Characteristic Chromosomal or Other Global Mutational Patterns
Put your text here and fill in the table (Instructions: Included in this category are alterations such as hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis; microsatellite instability; homologous recombination deficiency; mutational signature pattern; etc. 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.)
| Chromosomal Pattern | Molecular Pathogenesis | Prevalence -
Common >20%, Recurrent 5-20% or Rare <5% (Disease) |
Diagnostic, Prognostic, and Therapeutic Significance - D, P, T | Established Clinical Significance Per Guidelines - Yes or No (Source) | Clinical Relevance Details/Other Notes |
|---|---|---|---|---|---|
| EXAMPLE:
Co-deletion of 1p and 18q |
EXAMPLE: See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference). | EXAMPLE: Common (Oligodendroglioma) | EXAMPLE: D, P | ||
| EXAMPLE:
Microsatellite instability - hypermutated |
EXAMPLE: Common (Endometrial carcinoma) | EXAMPLE: P, T | |||
editv4:Characteristic Chromosomal Aberrations / PatternsThe content below was from the old template. Please incorporate above.
The t(1;19) translocation can be balanced or unbalanced. The unbalanced form has a der(19) resulting in trisomy of 1q distal to PBX1.[10]
End of V4 Section
Gene Mutations (SNV/INDEL)
Secondary somatic copy number aberrations are not frequently seen in TCF3-PBX1 B-ALL[11].
Put your text here and fill in the table (Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent or common as well either disease defining and/or clinically significant. If a gene has multiple mechanisms depending on the type or site of the alteration, add multiple entries in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable; Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity. Details on clinical significance such as prognosis and other important information such as concomitant and mutually exclusive mutations can be provided in the notes section. Please include references throughout the table. Do not delete the table.)
| Gene | Genetic Alteration | Tumor Suppressor Gene, Oncogene, Other | Prevalence -
Common >20%, Recurrent 5-20% or Rare <5% (Disease) |
Diagnostic, Prognostic, and Therapeutic Significance - D, P, T | Established Clinical Significance Per Guidelines - Yes or No (Source) | Clinical Relevance Details/Other Notes |
|---|---|---|---|---|---|---|
| PHF6
|
EXAMPLE: Exon 18-21 activating mutations | Transcription factor | Recurrent[12] | D: N/A
T: N/A T: N/A |
No (NCCN) | |
| PAX5
|
EXAMPLE: Variable LOF mutations | Transcription factor | EXAMPLE: Common (breast cancer) | EXAMPLE: P | EXAMPLE: >90% are somatic; rare germline alterations associated with Li-Fraumeni syndrome (add reference). Denotes a poor prognosis in breast cancer. | |
Note: A more extensive list of mutations can be found in cBioportal, COSMIC, and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
Epigenomic Alterations
Put your text here
Genes and Main Pathways Involved
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 [13][14][9]
| Gene; Genetic Alteration | Pathway | Pathophysiologic Outcome |
|---|---|---|
| WNT signaling | Increased cell-proliferation, survival and chemotaxis |
Genetic Diagnostic Testing Methods
- Conventional chromosome analysis with FISH confirmation
- RT-PCR
- DNA or RNA based NGS analysis [9]
Familial Forms
Put your text here (Instructions: Include associated hereditary conditions/syndromes that cause this entity or are caused by this entity.)
Additional Information
A karyotypically identical t(1;19) has been observed in a subset of B-ALL cases, especially in hyperdiploid B-ALL. This translocation does not involve TCF3 or PBX1. Therefore, a FISH confirmation is often necessary to determine the nature of t(1;19). [14][9]
Links
References
- ↑ LeBrun, David P. (2003-05-01). "E2A basic helix-loop-helix transcription factors in human leukemia". Frontiers in Bioscience: A Journal and Virtual Library. 8: s206–222. doi:10.2741/1030. ISSN 1093-9946. PMID 12700034.
- ↑ Lin, Chiou-Hong; Wang, Zhong; Duque-Afonso, Jesús; Wong, Stephen Hon-Kit; Demeter, Janos; Loktev, Alexander V.; Somervaille, Tim C. P.; Jackson, Peter K.; Cleary, Michael L. (2019-03-20). "Oligomeric self-association contributes to E2A-PBX1-mediated oncogenesis". Scientific Reports. 9 (1): 4915. doi:10.1038/s41598-019-41393-w. ISSN 2045-2322. PMC 6426973. PMID 30894657.
- ↑ Burmeister, Thomas; Gökbuget, Nicola; Schwartz, Stefan; Fischer, Lars; Hubert, Daniela; Sindram, Annette; Hoelzer, Dieter; Thiel, Eckhard (2010-02). "Clinical features and prognostic implications of TCF3-PBX1 and ETV6-RUNX1 in adult acute lymphoblastic leukemia". Haematologica. 95 (2): 241–246. doi:10.3324/haematol.2009.011346. ISSN 1592-8721. PMC 2817026. PMID 19713226.
{{cite journal}}: Check date values in:|date=(help) - ↑ Felice, María S.; Gallego, Marta S.; Alonso, Cristina N.; Alfaro, Elizabeth M.; Guitter, Myriam R.; Bernasconi, Andrea R.; Rubio, Patricia L.; Zubizarreta, Pedro A.; Rossi, Jorge G. (2011-07). "Prognostic impact of t(1;19)/ TCF3-PBX1 in childhood acute lymphoblastic leukemia in the context of Berlin-Frankfurt-Münster-based protocols". Leukemia & Lymphoma. 52 (7): 1215–1221. doi:10.3109/10428194.2011.565436. ISSN 1029-2403. PMID 21534874.
{{cite journal}}: Check date values in:|date=(help) - ↑ Lin, Anna; Cheng, Frankie W. T.; Chiang, Alan K. S.; Luk, Chung-Wing; Li, Rever C. H.; Ling, Alvin S. C.; Cheuk, Daniel K. L.; Chang, Kai-On; Ku, Dennis (2018-12). "Excellent outcome of acute lymphoblastic leukaemia with TCF3-PBX1 rearrangement in Hong Kong". Pediatric Blood & Cancer. 65 (12): e27346. doi:10.1002/pbc.27346. ISSN 1545-5017. PMID 30051646.
{{cite journal}}: Check date values in:|date=(help)CS1 maint: article number as page number (link) - ↑ Yilmaz, Musa; Kantarjian, Hagop M.; Toruner, Gokce; Yin, C. Cameron; Kanagal-Shamanna, Rashmi; Cortes, Jorge E.; Issa, Ghayyas; Short, Nicholas J.; Khoury, Joseph D. (2021-01). "Translocation t(1;19)(q23;p13) in adult acute lymphoblastic leukemia - a distinct subtype with favorable prognosis". Leukemia & Lymphoma. 62 (1): 224–228. doi:10.1080/10428194.2020.1824071. ISSN 1029-2403. PMC 11648456. PMID 32955970.
{{cite journal}}: Check date values in:|date=(help) - ↑ Jeha, Sima; Choi, John; Roberts, Kathryn G.; Pei, Deqing; Coustan-Smith, Elaine; Inaba, Hiroto; Rubnitz, Jeffrey E.; Ribeiro, Raul C.; Gruber, Tanja A. (2021-07). "Clinical significance of novel subtypes of acute lymphoblastic leukemia in the context of minimal residual disease-directed therapy". Blood Cancer Discovery. 2 (4): 326–337. doi:10.1158/2643-3230.bcd-20-0229. ISSN 2643-3249. PMC 8265990. PMID 34250504.
{{cite journal}}: Check date values in:|date=(help) - ↑ Jeha, S.; Pei, D.; Raimondi, S. C.; Onciu, M.; Campana, D.; Cheng, C.; Sandlund, J. T.; Ribeiro, R. C.; Rubnitz, J. E. (2009-08). "Increased risk for CNS relapse in pre-B cell leukemia with the t(1;19)/TCF3-PBX1". Leukemia. 23 (8): 1406–1409. doi:10.1038/leu.2009.42. ISSN 1476-5551. PMC 2731684. PMID 19282835.
{{cite journal}}: Check date values in:|date=(help) - ↑ 9.0 9.1 9.2 9.3 9.4 Akkari, Yassmine M. N.; Bruyere, Helene; Hagelstrom, R. Tanner; Kanagal-Shamanna, Rashmi; Liu, Jie; Luo, Minjie; Mikhail, Fady M.; Pitel, Beth A.; Raca, Gordana (05 2020). "Evidence-based review of genomic aberrations in B-lymphoblastic leukemia/lymphoma: Report from the cancer genomics consortium working group for lymphoblastic leukemia". Cancer Genetics. 243: 52–72. doi:10.1016/j.cancergen.2020.03.001. ISSN 2210-7762. PMID 32302940.
{{cite journal}}: Check date values in:|date=(help) - ↑ Meloni-Ehrig A., (2013). The principles of clinical cytogenetics. 3rd edition. Steven L. Gersen and Martha B. Keagle , Editors. Springer. DOI 10.1007/978-1-4419-1688-4. p327-329.
- ↑ WHO Classification of Tumours: Haematolymphoid Tumours [Internet; Beta Version Ahead of Print](5th ed.), International Agency for Research on Cancer (2022)
- ↑ Ueno, Hiroo; Yoshida, Kenichi; Shiozawa, Yusuke; Nannya, Yasuhito; Iijima-Yamashita, Yuka; Kiyokawa, Nobutaka; Shiraishi, Yuichi; Chiba, Kenichi; Tanaka, Hiroko (2020-10-27). "Landscape of driver mutations and their clinical impacts in pediatric B-cell precursor acute lymphoblastic leukemia". Blood Advances. 4 (20): 5165–5173. doi:10.1182/bloodadvances.2019001307. ISSN 2473-9537. PMC 7594377. PMID 33095873.
- ↑ Diakos, Christofer; Xiao, Yuanyuan; Zheng, Shichun; Kager, Leo; Dworzak, Michael; Wiemels, Joseph L. (2014). "Direct and indirect targets of the E2A-PBX1 leukemia-specific fusion protein". PloS One. 9 (2): e87602. doi:10.1371/journal.pone.0087602. ISSN 1932-6203. PMC 3913655. PMID 24503810.
{{cite journal}}: CS1 maint: article number as page number (link) CS1 maint: unflagged free DOI (link) - ↑ 14.0 14.1 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
Notes
*Citation of this Page: Mancera MG. “B lymphoblastic leukaemia/lymphoma with TCF3::PBX1 fusion”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 02/17/2026, https://ccga.io/index.php/HAEM5:B_lymphoblastic_leukaemia/lymphoma_with_TCF3::PBX1_fusion.
*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.
Prior Author(s): Binu Porath, PhD; Linda D. Cooley, MD, MBA