HAEM5: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. Oligomerization and/or direct interaction with HOX proteins through the PBX1 moiety may play a role in TCF3-PBX1 leukemogenesis.	t(1;19)(q23;q13.3)	Ubiquitous	D: Requires demonstration of TCF3::PBX1 rearrangement P: Associated with intermediate to relatively favorable clinical outcomes. 5-year event-free survival (80-88.2%). T: N/A	No (NCCN)	There may be an increased relative risk of CNS relapse in these patients. 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.

The breakpoints of the t(1;19) translocation typically fall within intron 16 of TCF3 and intron 3 of PBX1.

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 / Patterns

The 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.

End of V4 Section

---

Gene Mutations (SNV/INDEL)

Secondary somatic copy number aberrations are not frequently seen in TCF3-PBX1 B-ALL.

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	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

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

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).

Links

TCF3

PBX1

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