t(1;19)(q23;p13) TCF3/PBX1

2012-07-01   Cristina N Alonso 

1.Hematology-Oncology Department, Hospital Nacional de Pediatria Garrahan, Combate de los Pozos 1881- Zip Code : 1245. Buenos Aires, Republica Argentina
2.Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers France

Clinics and Pathology


B Lymphoblastic leukemia/lymphoma with t(1;19)(q23;p13.3); E2A-PBX1 (TCF3-PBX1); mostly found in ALL, L1/L2 type; exceptionally found in L3-like ALL, T-ALL, NHL, or AML.

Phenotype stem cell origin

Most cases: pre B (cIg+) ALL; may be cIg- or sIg+.
CD45dim, CD19pos, CD34neg, CD22pos/dim, CD20dim/pos, CD24pos, TdTpos, CD10neg/dim, cIgMpos, CD9pos, CD15neg, CD65neg, CD66cneg, CD13neg, CD33neg.


5% of ALL, or 20% of pre B ALL; found in children and young adults (1-60 yrs, median: 10 yrs --> one of the most frequent ALL in childhood (4-6%)); 3 male/4 female patients.


Moderate organomegaly; frequent CNS involvement; blood data: high WBC (median 20 x 109/L); high LDH.


Treatment should be adapted to biological features at the moment of diagnosis and also to early chemotherapy response and risk group stratification should not be based on TCF3-PBX1 detection.


Although this chromosomal abnormality usually discloses adverse prognostic features (WBC, SNC), it is associated with good prognosis with modern intensive protocols. Median 5 yr-event free survival probability in childhood ALL: 85(6)%; no age or blood data prognostic significance; there are no differences between the prognosis of balanced or unbalanced forms. Prognosis in adults is not different between TCF3-PBX1 positive and negative cases (pEFS: 40 vs. 44%).


Cytogenetics morphological

Breakpoint is in 19p13.3; two different forms (see diagrams above): - the balanced t(1;19), one fourth of cases, with a der(1) and a der(19); - the unbalanced form, found in 3/4 cases, with 2 normal chromosomes 1, a der(19), and 1 normal chromosome 19: --> partial trisomy for 1q23-1qter and monosomy for 19p13.3-pter; the 2 forms can be in mosaic; note: 19p13 and 19q13 may be confused (e.g. literature reports). A subset of ALL usually hyperdyploid B-ALL has an identical t(1;19) that lack the expected phenotype probably do not represent TCF3-PBX1 B-ALL.

Additional anomalies

t(17;19)(q22;p13) is not stricto sensu a variant, but, so far, an equivalent, with HLF (hepatic leukemia factor), on 17q22, involved in the translocation. Additional anomalies are found in half of the cases, mostly partial dup (1q), +6, del(6q), +8, i(9q), +17, i(17q), +21.

Genes Involved and Proteins

The following are (most often) involved, except in some cases lacking the cIg expression:
Gene name
PBX1 (pre-B-cell leukemia homeobox 1)
Previously known as "pre-B-cell leukemia transcription factor 1".
Dna rna description
Alternate splicing (variants 1, 2 and 3) (Acc Numbers: NM_001204963.1, NM_001204961.1 and NM_002585.3).
Atlas Image
c-PBX1 at 1q23 in normal cells: PAC 1146N1 - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.
Protein description
Nuclear protein that belongs to the PBX homeobox family of transcriptional factors. Contains a homeodomain to bind to DNA.
Gene name
TCF3 (transcription factor 3 (E2A immunoglobulin enhancer binding factors E12/E47))
Other names: bHLHb21, E2A, "E2A immunoglobulin enhancer-binding factor E12/E47", E47, "immunoglobulin transcription factor 1", ITF1, "kappa-E2-binding factor", MGC129647, MGC129648, "transcription factor E2-alpha", VDIR, "VDR interacting repressor".
Dna rna description
Alternate splicing 2 isoforms --> E12 and E47. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the short arm of chromosome 9.
Protein description
Contains transcriptional activation domains and a basic helix-loop-helix DNA binding site; binds specifically to an immunoglobulin enhancer; nuclear localization; transcription factor.

Result of the Chromosomal Anomaly


5 TCF3 exons fused to 3 PBX1; breakpoints are clustered on both genes; the reciprocal 5 PBX1 - 3 E2A is not transcribed.


Most cases present fusion of exons 1-16 in TCF3 to exons 4-9 in PBX1. Alternative breakpoint in intron 4 of PBX1, not detectable by standardized RT-PCR primers, has been reported.
Atlas Image


550 amino acids; 85 kDa; N-term transcriptional activation domains from TCF3 fused to the Hox cooperative motif and homeodomain of C-term PBX1; potent transcriptional activator.

Expression localisation

Nuclear localisation.


Pleiotropic transforming activity. The resulting fusion protein (TCF3-PBX1), in which the DNA binding domain of E2A is replaced by the DNA binding domain of TCF3, transforms cells by constitutively activating transcription of genes regulated by PBX1 or by other members the PBX protein family.

Highly cited references

Pubmed IDYearTitleCitations
262145922015Genomics and drug profiling of fatal TCF3-HLF-positive acute lymphoblastic leukemia identifies recurrent mutation patterns and therapeutic options.79
304872232018Transcriptional landscape of B cell precursor acute lymphoblastic leukemia based on an international study of 1,223 cases.75
276342052017ZNF384-related fusion genes define a subgroup of childhood B-cell precursor acute lymphoblastic leukemia with a characteristic immunotype.58
247810172014A revised definition for cure of childhood acute lymphoblastic leukemia.45
289725942018RAS pathway mutations as a predictive biomarker for treatment adaptation in pediatric B-cell precursor acute lymphoblastic leukemia.37
305100822019Novel susceptibility variants at the ERG locus for childhood acute lymphoblastic leukemia in Hispanics.23
248111612014Targeting the B-cell receptor signaling pathway in B lymphoid malignancies.21
287091342017BCR-ABL1-like acute lymphoblastic leukaemia: From bench to bedside.19
314347062019The preleukemic TCF3-PBX1 gene fusion can be generated in utero and is present in ≈0.6% of healthy newborns.18
319020362020Insights into the prenatal origin of childhood acute lymphoblastic leukemia.18
276984472017Long-term outcome of 6-month maintenance chemotherapy for acute lymphoblastic leukemia in children.18
321506102020The application of RNA sequencing for the diagnosis and genomic classification of pediatric acute lymphoblastic leukemia.17
275905212016Deep targeted sequencing in pediatric acute lymphoblastic leukemia unveils distinct mutational patterns between genetic subtypes and novel relapse-associated genes.17
306311482019Wnt5a and ROR1 activate non-canonical Wnt signaling via RhoA in TCF3-PBX1 acute lymphoblastic leukemia and highlight new treatment strategies via Bcl-2 co-targeting.16
295892812018Treatment outcome of children with acute lymphoblastic leukemia: the Tokyo Children's Cancer Study Group (TCCSG) Study L04-16.14
262370752015Epigenetic landscape correlates with genetic subtype but does not predict outcome in childhood acute lymphoblastic leukemia.14
324671452021Philadelphia-like acute lymphoblastic leukemia is associated with minimal residual disease persistence and poor outcome. First report of the minimal residual disease-oriented GIMEMA LAL1913.13
274610632017Idelalisib sensitivity and mechanisms of disease progression in relapsed TCF3-PBX1 acute lymphoblastic leukemia.13
342505042021Clinical significance of novel subtypes of acute lymphoblastic leukemia in the context of minimal residual disease-directed therapy.12
302091202018Murine pre-B-cell ALL induces T-cell dysfunction not fully reversed by introduction of a chimeric antigen receptor.12
276118672016The Expression Pattern of the Pre-B Cell Receptor Components Correlates with Cellular Stage and Clinical Outcome in Acute Lymphoblastic Leukemia.12
301257572018Retrospective analysis of 36 fusion genes in 2479 Chinese patients of de novo acute lymphoblastic leukemia.8
262775492015Frequency of copy number abnormalities in common genes associated with B-cell precursor acute lymphoblastic leukemia cytogenetic subtypes in Brazilian children.8
241350882013Translocation junctions in TCF3-PBX1 acute lymphoblastic leukemia/lymphoma cluster near transposable elements.8
338958092021Molecular classification improves risk assessment in adult BCR-ABL1-negative B-ALL.7
252735582014Predicting interactome network perturbations in human cancer: application to gene fusions in acute lymphoblastic leukemia.7
245783042014Outcome of TCF3-PBX1 positive pediatric acute lymphoblastic leukemia patients in Japan: a collaborative study of Japan Association of Childhood Leukemia Study (JACLS) and Children's Cancer and Leukemia Study Group (CCLSG).7
251370602014Genomic inverse PCR for exploration of ligated breakpoints (GIPFEL), a new method to detect translocations in leukemia.7
330958732020Landscape of driver mutations and their clinical impacts in pediatric B-cell precursor acute lymphoblastic leukemia.6
313050092019Resistance of t(17;19)-acute lymphoblastic leukemia cell lines to multiagents in induction therapy.6
293342552018NGS-based methylation profiling differentiates TCF3-HLF and TCF3-PBX1 positive B-cell acute lymphoblastic leukemia.6
328820242021Genome-Wide Association Study of Susceptibility Loci for TCF3-PBX1 Acute Lymphoblastic Leukemia in Children.5
288532182018Mutational status of NRAS, KRAS, and PTPN11 genes is associated with genetic/cytogenetic features in children with B-precursor acute lymphoblastic leukemia.5
276329782016Multiplexed automated digital quantification of fusion transcripts: comparative study with fluorescent in-situ hybridization (FISH) technique in acute leukemia patients.5
345974662022Clonal dynamics in pediatric B-cell precursor acute lymphoblastic leukemia with very early relapse.4
331649842020Pharmacogenomics of intracellular methotrexate polyglutamates in patients' leukemia cells in vivo.4
333865962021The role of minimal residual disease in specific subtypes of pediatric acute lymphoblastic leukemia.4
323688312020Impact of immunophenotypic characteristics on genetic subgrouping in childhood acute lymphoblastic leukemia: Tokyo Children's Cancer Study Group (TCCSG) study L04-16.4
307306142019Flow cytometric predictive scoring systems for common fusions ETV6/RUNX1, BCR/ABL1, TCF3/PBX1 and rearrangements of the KMT2A gene, proposed for the initial cytogenetic approach in cases of B-acute lymphoblastic leukemia.4
300516462018Excellent outcome of acute lymphoblastic leukaemia with TCF3-PBX1 rearrangement in Hong Kong.4
304798722018Early vs. late MRD response- and risk-based treatment intensification of childhood acute lymphoblastic leukemia: a prospective pilot study from Saudi Arabia.4
274315732016Regulation of the miRNA expression by TEL/AML1, BCR/ABL, MLL/AF4 and TCF3/PBX1 oncoproteins in acute lymphoblastic leukemia (Review).4
255512712015Clinical features and prognostic significance of TCF3-PBX1 fusion gene in Chinese children with acute lymphoblastic leukemia by using a modified ALL-BFM-95 protocol.4
350844342022Association of Genetic Ancestry With the Molecular Subtypes and Prognosis of Childhood Acute Lymphoblastic Leukemia.3
323788102020High incidence of RAS pathway mutations among sentinel genetic lesions of Korean pediatric BCR-ABL1-like acute lymphoblastic leukemia.3
320298382020Clinicopathological features and prognostic value of SOX11 in childhood acute lymphoblastic leukemia.3
284761982016Copy Number Alterations Associated with Acute Lymphoblastic Leukemia in Mexican Children. A report from The Mexican Inter-Institutional Group for the identification of the causes of childhood leukemia.3
266488362015Cytogenetic and Molecular Findings in Children with Acute Lymphoblastic Leukemia: Experience of a Single Institution in Argentina.3
349333432022Whole-transcriptome analysis in acute lymphoblastic leukemia: a report from the DFCI ALL Consortium Protocol 16-001.2
340349132021Clinical features and prognostic impact of TCF3-PBX1 in childhood acute lymphoblastic leukemia: A single-center retrospective study of 837 patients from China.2
337502582021Genomic landscape of B-other acute lymphoblastic leukemia in an adult retrospective cohort with a focus on BCR-ABL1-like subtype.2
329840142020A Nomogram for the Prediction of Progression and Overall Survival in Childhood Acute Lymphoblastic Leukemia.2
303697272018Keeping PACE with Ph Positive to Ph-Like Detection in B-Lineage Acute Lymphoblastic Leukemia: A Practical and Cost Effective (PACE) Approach in a Resource Constrained Setting.2
284365812017Pediatric acute lymphoblastic leukemia with t(1;19)/TCF3-PBX1 in Taiwan.2
280637222017Concordance of two approaches in monitoring of minimal residual disease in B-precursor acute lymphoblastic leukemia: Fusion transcripts and leukemia-associated immunophenotypes.2
251161872014Impact of TCF3 rearrangement on CNS relapse in egyptian pediatric acute lymphoblastic leukemia.2
257295752015A (1;19) translocation involving TCF3-PBX1 fusion within the context of a hyperdiploid karyotype in adult B-ALL: a case report and review of the literature.2
344601332022Cryptic TCF3 fusions in childhood leukemia: Detection by RNA sequencing.1
345494162022Prognostic heterogeneity of adult B-cell precursor acute lymphoblastic leukaemia patients with t(1;19)(q23;p13)/TCF3-PBX1 treated with measurable residual disease-oriented protocols.1
344067032021The clinical outcomes and genomic landscapes of acute lymphoblastic leukemia patients with E2A-PBX1: A 10-year retrospective study.1
338162702021The Prognostic Significance of ZNF384 Fusions in Adult Ph-Negative B-Cell Precursor Acute Lymphoblastic Leukemia: A Comprehensive Cohort Study From a Single Chinese Center.1
318285952020Multiple heterogeneous bone invasions of B lymphoblastic lymphoma with the TCF3/PBX1 fusion gene: a case report.1
319445722020CD304/neuropilin-1 is a very useful and dependable marker for the measurable residual disease assessment of B-cell precursor acute lymphoblastic leukemia.1
315758522019Characterization of TCF3 rearrangements in pediatric B-lymphoblastic leukemia/lymphoma by mate-pair sequencing (MPseq) identifies complex genomic rearrangements and a novel TCF3/TEF gene fusion.1
315061482019[Long-term clinical effect of the CCLG-ALL2008 regimen in treatment of childhood acute lymphoblastic leukemia with different molecular biological features].1
308099812019The Incidence and Immunophenotypic and Genetic Features of JL1 Expressing Cells and the Therapeutic Potential of an Anti-JL1 Antibody in De Novo Pediatric Acute Leukemias.1
307014582019Molecular profiling of adult acute myeloid and lymphoid leukemia in a major referral center in Lebanon: a 10-year experience report and review of the literature.1
283851562017Childhood pre-B cell acute lymphoblastic leukemia with translocation t(1;19)(q21.1;p13.3) and two additional chromosomal aberrations involving chromosomes 1, 6, and 13: a case report.1
280289662016Glycogen Synthase Kinase-3β (GSK-3β) and Nuclear Factor Kappa-B (NFKB) in Childhood Acute Lymphoblastic Leukemia.1
262665192015High frequency and poor prognosis of late childhood BCR-ABL-positive and MLL-AF4-positive ALL define the need for advanced molecular diagnostics and improved therapeutic strategies in pediatric B-ALL in Pakistan.1
231905782013Interphase-FISH screening for eight common rearrangements in pediatric B-cell precursor acute lymphoblastic leukemia.1
353444692022Adult acute lymphoblastic leukemia in a resource-constrained setting: outcomes after expansion of genetic evaluation.0
360112852022Commonly Assessed Markers in Childhood BCP-ALL Diagnostic Panels and Their Association with Genetic Aberrations and Outcome Prediction.0
35782267202218F-FDG PET/CT for the detection of extensive bone relapse in acute lymphoblastic leukemia with TCF3-PBX1 fusion after hematopoietic stem cell transplantation.0
357199522022Underexpression of LINC00173 in TCF3/PBX1-Positive Cases Is Associated With Poor Prognosis in Children With B-Cell Precursor Acute Lymphoblastic Leukemia.0
348713732022Impact of high-risk cytogenetics on outcomes for children and young adults receiving CD19-directed CAR T-cell therapy.0
351257242022Incidence and Prognostic Impact of TCF3-PBX1 Fusion in Childhood Acute Lymphoblastic Leukemia: A Single Centre Experience.0
343250572021Comparison of Two Quantitative PCR-Based Assays for Detection of Minimal Residual Disease in B-Precursor Acute Lymphoblastic Leukemia Harboring Three Major Fusion Transcripts.0
356859212022Low Prevalence of ETV6::RUNX1 Fusion Gene in a Hispanic Population.0
345538422021Genetic features of B-cell lymphoblastic lymphoma with TCF3-PBX1.0
355629652022Multi-Cohort Transcriptomic Subtyping of B-Cell Acute Lymphoblastic Leukemia.0
350926532022MicroRNA gene methylation landscape in pediatric B-cell precursor acute lymphoblastic leukemia.0
346174332022Characterization of Immunophenotypic Aberrancies with Respect to Common Fusion Transcripts in B-Cell Precursor Acute Lymphoblastic Leukemia: A Report of 986 Indian Patients0
337253182021Clinical features and chromosomal/genetic aberration in adult acute lymphoblastic leukemia in Japan: results of Fukuoka Blood & Marrow Transplant Group Studies ALL MRD 2002 and 2008.0
340497152021Expression of BCL6 in paediatric B-cell acute lymphoblastic leukaemia and association with prognosis.0
347716462021Towards Raman-Based Screening of Acute Lymphoblastic Leukemia-Type B (B-ALL) Subtypes.0
358451832021Cytogenetic aberrations in adult acute lymphoblastic leukemia-A population-based study.0
341594012021Hematological characteristics, cytogenetic features, and post-induction measurable residual disease in thymic stromal lymphopoietin receptor (TSLPR) overexpressed B-cell acute lymphoblastic leukemia in an Indian cohort.0
343483052021Cytogenetic and Fluorescence in situ Hybridization Profile of Pediatric Acute Lymphoblastic Leukemia in a University Hospital in South India.0
338907262021CRLF2 and IKZF1 abnormalities in Mexican children with acute lymphoblastic leukemia and recurrent gene fusions: exploring surrogate markers of signaling pathways.0
332837062020[The Correlation of Minimal Residual Disease with Prognosis in TCF3-PBX1+ Acute Lymphoblastic Leukemia in Children].0
339879752021Subgrouping by gene expression profiles to improve relapse risk prediction in paediatric B-precursor acute lymphoblastic leukaemia.0
325639102020Ibrutinib is not an effective drug in primografts of TCF3-PBX1.0
336463062021Genome-wide interference of ZNF423 with B-lineage transcriptional circuitries in acute lymphoblastic leukemia.0
336630972021Co-occurrence of TCF3-PBX1 gene fusion, and chromosomal aberration in a pediatric pre-B cell acute lymphoblastic leukemia with clitoris swelling: A case report and literature review.0
332211502021Long-Term Results of the Risk-Stratified Treatment of TCF3-PBX1-Positive Pediatric Acute Lymphoblastic Leukemia in China.0
329559702021Translocation t(1;19)(q23;p13) in adult acute lymphoblastic leukemia - a distinct subtype with favorable prognosis.0
302625662019B-lymphoblastic lymphoma with TCF3-PBX1 fusion gene.0
305635232018A novel PAX5 rearrangement in TCF3-PBX1 acute lymphoblastic leukemia: a case report.0
259481772015[Cytogenetic characteristics of 163 children with acute lymphoblastic leukemia].0


Pubmed IDLast YearTitleAuthors
197132262010Clinical features and prognostic implications of TCF3-PBX1 and ETV6-RUNX1 in adult acute lymphoblastic leukemia.Burmeister T et al
145088192003The biology and therapy of adult acute lymphoblastic leukemia.Faderl S et al
215348742011Prognostic impact of t(1;19)/ TCF3-PBX1 in childhood acute lymphoblastic leukemia in the context of Berlin-Frankfurt-Münster-based protocols.Felice MS et al
120942482002Antigen expression patterns reflecting genotype of acute leukemias.Hrusák O et al
86082071996Chromosomal translocations involving the E2A gene in acute lymphoblastic leukemia: clinical features and molecular pathogenesis.Hunger SP et al
19679831990A new homeobox gene contributes the DNA binding domain of the t(1;19) translocation protein in pre-B ALL.Kamps MP et al
79109441994Fusion with E2A converts the Pbx1 homeodomain protein into a constitutive transcriptional activator in human leukemias carrying the t(1;19) translocation.Lu Q et al
20785151990Molecular analysis of the t(1;19) breakpoint cluster region in pre-B cell acute lymphoblastic leukemias.Mellentin JD et al
16827991991PBX2 and PBX3, new homeobox genes with extensive homology to the human proto-oncogene PBX1.Monica K et al
19679821990Chromosomal translocation t(1;19) results in synthesis of a homeobox fusion mRNA that codes for a potential chimeric transcription factor.Nourse J et al
157443502005Cloning and functional characterization of MEF2D/DAZAP1 and DAZAP1/MEF2D fusion proteins created by a variant t(1;19)(q23;p13.3) in acute lymphoblastic leukemia.Prima V et al
13484331992Different molecular consequences of the 1;19 chromosomal translocation in childhood B-cell precursor acute lymphoblastic leukemia.Privitera E et al
97183811998Acute lymphoblastic leukemia.Pui CH et al
79899351994Immunologic, cytogenetic, and clinical characterization of childhood acute lymphoblastic leukemia with the t(1;19) (q23; p13) or its derivative.Pui CH et al
15939011992Prognostic significance of the balanced t(1;19) and unbalanced der(19)t(1;19) translocations in acute lymphoblastic leukemia.Secker-Walker LM et al
77343491995Heterogeneity of t(1;19)(q23;p13) acute leukaemias. French Haematological Cytology Group.Troussard X et al
94693371998Clinical significance of translocation t(1;19) in childhood acute lymphoblastic leukemia in the context of contemporary therapies: a report from the Children's Cancer Group.Uckun FM et al


Fusion gene

TCF3/PBX1 TCF3 (19p13.3) PBX1 (1q23.3) COF 1489 1490 2121 2122 2123 2124 2125 2126 2127 2128 2129 2130 2131 2132 2133 2134 2135 2136 2137 2138 2140 2141 2142 2143 2144 2145 2146 2147|TCF3/PBX1 TCF3 (19p13.3) PBX1 (1q23.3) M der(19)t(1;19)(q23;p13) t(1;19)(q23;p13)|TCF3/PBX1 TCF3 (19p13.3) PBX1 (1q23.3) TIC


Balanced form: -1, -19, +der(1), +der(19); unbalanced form: -19, +der(19).
Atlas Image
t(1;19)(q23;p13) TCF3/PBX1  (A): Unbalanced form: der(19) t(1;19)(q23;p13) G-banding; top - Courtesy Jean-Luc Lai; others - Courtesy Adriana Zamecnikova; and R-banding; top: - Jean Loup Huret, below: - Courtesy Christiane Charrin. (B): Balanced form: t(1;19)(q23;p13) - Courtesy Jean-Luc Lai; bottom: - Courtesy Adriana Zamecnikova. Fluorescence in situ hybridization on metaphases using the LSI TCF3/PBX1 Dual Color, Dual Fusion Translocation Probe (Vysis/Abbott Molecular, US) on (C): normal metaphase and confirming the presence of the TCF3-PBX1 gene fusion on (D): unbalanced der(19)t(1;19)(q23;p13.3) or (E): balanced t(1;19)(q23;p13) - Courtesy Adriana Zamecnikova.


Cristina N Alonso

t(1;19)(q23;p13) TCF3/PBX1

Atlas Genet Cytogenet Oncol Haematol. 2012-07-01

Online version: http://atlasgeneticsoncology.org/haematological/1048/t(1;19)(q23;p13)

Historical Card

1997-10-01 t(1;19)(q23;p13) TCF3/PBX1 by  Jean-Loup Huret 

Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers France