B-Lymphoblastic Leukemia/Lymphoma with t(1;19)(q23;p13.3); TCF3-PBX1

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Primary Author(s)*

Binu Porath, PhD. Vanderbilt University Medical Center, Nashville, TN

Linda D. Cooley, MD, MBA. Children's Mercy Kansas City, Kansas City, MO

Cancer Category/Type

B-Lymphoblastic Leukemia/Lymphoma

Cancer Sub-Classification / Subtype

B-Lymphoblastic Leukemia/Lymphoma with t(1;19)(q23;p13.3); TCF3-PBX1

Definition / Description of Disease

Neoplasm of B-cell lineage precursor lymphoblasts where the blasts contain a translocation between PBX1 at 1q23 and TCF3 at 19p13.3.[1]

Synonyms / Terminology

TCF3 is also known as E2A.

Epidemiology / Prevalence

The t(1;19) translocation is present in ~5% pediatric and ~3% adult B-ALL cases. The incidence of this translocation does not vary significantly with age, however, there is a high incidence (~12%) of this rearrangement in African-American children with B-ALL.[2]

Clinical Features

No unique clinical features that distinguish this entity from other types of B-ALL. Common clinical features of B-ALL include:

  • Fatigue
  • Infections
  • Easy bruising/bleeding

Other symptoms present may include:

  • Achiness
  • Fever
  • Night sweats
  • Weight loss

These features manifest clinically as anemia, neutropenia, and/or thrombocytopenia. [2]

Sites of Involvement

Bone marrow, Blood, Central Nervous System (CNS) [2]

Morphologic Features

There are no unique morphological features that distinguish this entity from other types of ALL.[1]


Blasts with pre-B phenotype, positive for CD19, CD10 and cytoplasmic mu heavy chain. [1]

Chromosomal Rearrangements (Gene Fusions)

The breakpoints of the t(1;19) translocation typically fall within intron 16 of TCF3 and intron 3 of PBX1. [2]

Chromosomal Rearrangement Genes in Fusion (5’ or 3’ Segments) Pathogenic Derivative Prevalence
t(1;19)(q23;p13.3) TCF3-PBX1 der(19) More common (75%)
t(1;19)(q23;p13.3) TCF3-PBX1 Balanced translocation Less common

Characteristic Chromosomal Aberrations / Patterns

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.[3]

Genomic Gain/Loss/LOH

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

Gene Mutations (SNV/INDEL)

Secondary somatic DNA mutations are not frequently seen in TCF3-PBX1 B-ALL. [2]

Other Mutations

Secondary somatic copy number aberrations and DNA mutations are not frequently seen in TCF3-PBX1 B-ALL, commonly found additional abnormalities are listed below. [2][3]

Type Gene/Region/Other
Additional abnormalities dup(1q), del(6q), +8, i(9q), i(17q), +21

Epigenomics (Methylation)

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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 [4][1][2]

Diagnostic Testing Methods

  • Conventional chromosome analysis with FISH confirmation
  • RT-PCR
  • DNA or RNA based NGS analysis [2]

Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)

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. [1][2][5]

Familial Forms

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Other Information

  • Another translocation involving the TCF3 gene is t(17;19) which results in the fusion of HLF at 17q22 with TCF3. This variant translocation has been reported in approximately 1% of pediatric B-ALL patients and is associated with a poor prognosis. [1][3]
  • 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). [1][2]




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  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 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
  2. 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 2.9 Akkari, Yassmine M. N.; et al. (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 Check |pmid= value (help). Check date values in: |date= (help)
  3. 3.0 3.1 3.2 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.
  4. Diakos, Christofer; et al. (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.
  5. Jeha, Sima; et al. (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 Check |pmc= value (help). PMID 34250504 Check |pmid= value (help). Check date values in: |date= (help)



  1. Arber DA, et al., (2008). Acute myeloid leukaemia with recurrent genetic abnormalities, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW, Editors. IARC Press: Lyon, France, p117-118.


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