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

Disease

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.

Epidemiology

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.

Clinics

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

Treatment

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.

Prognosis

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

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

Note
The following are (most often) involved, except in some cases lacking the cIg expression:
Gene name
PBX1 (pre-B-cell leukemia homeobox 1)
Location
1q23.3
Note
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))
Location
19p13.3
Note
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

Description

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

Transcript

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

Description

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.

Oncogenesis

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
248111612014Targeting the B-cell receptor signaling pathway in B lymphoid malignancies.90
393773972024Integrated multi-omics analysis of PBX1 in mouse adult neural stem- and progenitor cells identifies a transcriptional module that functionally links PBX1 to TCF3/4.89
252735582014Predicting interactome network perturbations in human cancer: application to gene fusions in acute lymphoblastic leukemia.86
262145922015Genomics and drug profiling of fatal TCF3-HLF-positive acute lymphoblastic leukemia identifies recurrent mutation patterns and therapeutic options.85
319020362020Insights into the prenatal origin of childhood acute lymphoblastic leukemia.82
360112852022Commonly Assessed Markers in Childhood BCP-ALL Diagnostic Panels and Their Association with Genetic Aberrations and Outcome Prediction.74
370199722023Etiology of oncogenic fusions in 5,190 childhood cancers and its clinical and therapeutic implication.71
338958092021Molecular classification improves risk assessment in adult BCR-ABL1-negative B-ALL.70
320298382020Clinicopathological features and prognostic value of SOX11 in childhood acute lymphoblastic leukemia.66
357199522022Underexpression of LINC00173 in TCF3/PBX1-Positive Cases Is Associated With Poor Prognosis in Children With B-Cell Precursor Acute Lymphoblastic Leukemia.65
366702352023Disruption to the FOXO-PRDM1 axis resulting from deletions of chromosome 6 in acute lymphoblastic leukaemia.60
338907262021CRLF2 and IKZF1 abnormalities in Mexican children with acute lymphoblastic leukemia and recurrent gene fusions: exploring surrogate markers of signaling pathways.59
399019412025Dynamic evolution of TCF3-PBX1 leukemias at the single-cell level under chemotherapy pressure.56
347716462021Towards Raman-Based Screening of Acute Lymphoblastic Leukemia-Type B (B-ALL) Subtypes.56
348713732022Impact of high-risk cytogenetics on outcomes for children and young adults receiving CD19-directed CAR T-cell therapy.55
383387542024CircRNAome of Childhood Acute Lymphoblastic Leukemia: Deciphering Subtype-Specific Expression Profiles and Involvement in TCF3::PBX1 ALL.54
349333432022Whole-transcriptome analysis in acute lymphoblastic leukemia: a report from the DFCI ALL Consortium Protocol 16-001.53
377046962023Molecular characterization of TCF3::PBX1 chromosomal breakpoints in acute lymphoblastic leukemia and their use for measurable residual disease assessment.53
368486372023Classification and genetics of pediatric B-other acute lymphoblastic leukemia by targeted RNA sequencing.53
390087162024A brain organoid/ALL coculture model reveals the AP-1 pathway as critically associated with CNS involvement of BCP-ALL.52
336463062021Genome-wide interference of ZNF423 with B-lineage transcriptional circuitries in acute lymphoblastic leukemia.52
355629652022Multi-Cohort Transcriptomic Subtyping of B-Cell Acute Lymphoblastic Leukemia.49
362331732022Normal and Aberrant TALE-Class Homeobox Gene Activities in Pro-B-Cells and B-Cell Precursor Acute Lymphoblastic Leukemia.47
342505042021Clinical significance of novel subtypes of acute lymphoblastic leukemia in the context of minimal residual disease-directed therapy.46
197132262010Clinical features and prognostic implications of TCF3-PBX1 and ETV6-RUNX1 in adult acute lymphoblastic leukemia.46
361244442023Clinical features and outcomes of fusion gene defined adult Ph-negative B-cell precursor acute lymphoblastic leukemia patients: A single institutional report.45
385987252024Development of combination therapies with BTK inhibitors and dasatinib to treat CNS-infiltrating E2A-PBX1+/preBCR+ ALL.44
373057202023Comprehensive genetic analyses of childhood acute leukemia in Iraq using next-generation sequencing.44
379810882024Transcriptome Sequencing Allows Comprehensive Genomic Characterization of Pediatric B-Acute Lymphoblastic Leukemia in an Academic Clinical Laboratory.43
392616012024Determinants of survival after first relapse of acute lymphoblastic leukemia: a Children's Oncology Group study.41
350844342022Association of Genetic Ancestry With the Molecular Subtypes and Prognosis of Childhood Acute Lymphoblastic Leukemia.41
356859212022Low Prevalence of ETV6::RUNX1 Fusion Gene in a Hispanic Population.40
313050092019Resistance of t(17;19)-acute lymphoblastic leukemia cell lines to multiagents in induction therapy.38
329840142020A Nomogram for the Prediction of Progression and Overall Survival in Childhood Acute Lymphoblastic Leukemia.38
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.37
385469162024Extracellular matrix protein 1 (ECM1) is a potential biomarker in B cell acute lymphoblastic leukemia.36
274610632017Idelalisib sensitivity and mechanisms of disease progression in relapsed TCF3-PBX1 acute lymphoblastic leukemia.32
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.32
366247862022Prognostic significance of steroid response in pediatric acute lymphoblastic leukemia: The CCCG-ALL-2015 study.32
304872232018Transcriptional landscape of B cell precursor acute lymphoblastic leukemia based on an international study of 1,223 cases.31
380232002023Retrospective analysis of outcomes for pediatric acute lymphoblastic leukemia in South American centers.31
329559702021Translocation t(1;19)(q23;p13) in adult acute lymphoblastic leukemia - a distinct subtype with favorable prognosis.30
346174332022Characterization of Immunophenotypic Aberrancies with Respect to Common Fusion Transcripts in B-Cell Precursor Acute Lymphoblastic Leukemia: A Report of 986 Indian Patients.29
325639102020Ibrutinib is not an effective drug in primografts of TCF3-PBX1.27
345538422022Genetic features of B-cell lymphoblastic lymphoma with TCF3-PBX1.27
328820242021Genome-Wide Association Study of Susceptibility Loci for TCF3-PBX1 Acute Lymphoblastic Leukemia in Children.25
305100822019Novel susceptibility variants at the ERG locus for childhood acute lymphoblastic leukemia in Hispanics.25
361140092022Extended vincristine and dexamethasone pulse therapy may not be necessary for children with TCF3-PBX1 positive acute lymphoblastic leukaemia.23
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.23
314347062019The preleukemic TCF3-PBX1 gene fusion can be generated in utero and is present in ≈0.6% of healthy newborns.22
351257242022Incidence and Prognostic Impact of TCF3-PBX1 Fusion in Childhood Acute Lymphoblastic Leukemia: A Single Centre Experience.20
302625662019B-lymphoblastic lymphoma with TCF3-PBX1 fusion gene.19
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).17
241350882013Translocation junctions in TCF3-PBX1 acute lymphoblastic leukemia/lymphoma cluster near transposable elements.17
305635232018A novel PAX5 rearrangement in TCF3-PBX1 acute lymphoblastic leukemia: a case report.17
384262882024Proteogenomic profiling uncovers differential therapeutic vulnerabilities between TCF3::PBX1 and TCF3::HLF translocated B-cell acute lymphoblastic leukemia.15
358451832021Cytogenetic aberrations in adult acute lymphoblastic leukemia-A population-based study.15
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.14
357822672022(18)F-FDG PET/CT for the detection of extensive bone relapse in acute lymphoblastic leukemia with TCF3-PBX1 fusion after hematopoietic stem cell transplantation.5
371203502023Emerging molecular subtypes and therapies in acute lymphoblastic leukemia.0
381060882023SINGLE CELL DISSECTION OF DEVELOPMENTAL ORIGINS AND TRANSCRIPTIONAL HETEROGENEITY IN B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA.0
374073632023Transcription factor abnormalities in B-ALL leukemogenesis and treatment.0
293342552018NGS-based methylation profiling differentiates TCF3-HLF and TCF3-PBX1 positive B-cell acute lymphoblastic leukemia.0
300516462018Excellent outcome of acute lymphoblastic leukaemia with TCF3-PBX1 rearrangement in Hong Kong.0
340349132021Clinical features and prognostic impact of TCF3-PBX1 in childhood acute lymphoblastic leukemia: A single-center retrospective study of 837 patients from China.0
284365812017Pediatric acute lymphoblastic leukemia with t(1;19)/TCF3-PBX1 in Taiwan.0
332211502021Long-Term Results of the Risk-Stratified Treatment of TCF3-PBX1-Positive Pediatric Acute Lymphoblastic Leukemia in China.0
274315732016Regulation of the miRNA expression by TEL/AML1, BCR/ABL, MLL/AF4 and TCF3/PBX1 oncoproteins in acute lymphoblastic leukemia (Review).0
393069172024Dysregulation of metallothionein MT1 sub-types in TCF3::PBX1 pre-B-cell acute lymphoblastic leukemia.0
370583242023TCF3 gene rearrangements in pediatric B-cell acute lymphoblastic leukemia-A single center experience.0
369437672023Prognostic factors of childhood acute lymphoblastic leukemia with TCF3::PBX1 in CCCG-ALL-2015: A multicenter study.0
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.0
175930262007Characterisation of genomic translocation breakpoints and identification of an alternative TCF3/PBX1 fusion transcript in t(1;19)(q23;p13)-positive acute lymphoblastic leukaemias.0
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.0
344601332022Cryptic TCF3 fusions in childhood leukemia: Detection by RNA sequencing.0
386631652024Real world outcome of B ALL with t (1; 19) (q23; p13)/TCF3::PBX1 in adolescents and adults treated with intensive regimes.0
287091342017BCR-ABL1-like acute lymphoblastic leukaemia: From bench to bedside.0
387197702024Evaluation of next-generation sequencing for measurable residual disease monitoring in three major fusion transcript subtypes of B-precursor acute lymphoblastic leukaemia.0
180244062007Incidence and outcome of TCF3-PBX1-positive acute lymphoblastic leukemia in Austrian children.0
378196862024A surrogate molecular approach for the detection of Philadelphia chromosome-like B-acute lymphoblastic leukemia.0
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.0
332837062020[The Correlation of Minimal Residual Disease with Prognosis in TCF3-PBX1(+) Acute Lymphoblastic Leukemia in Children].0
215348742011Prognostic impact of t(1;19)/ TCF3-PBX1 in childhood acute lymphoblastic leukemia in the context of Berlin-Frankfurt-Münster-based protocols.0
392660212024Case of B-acute lymphoblastic leukaemia with t(1;19)(q23;p13.3) TCF3::PBX1 and co-occurring CBL mutation in an elderly patient.0
378466762023[Clinical Significance of Minimal Residual Disease in Pediatric Patients with TCF3/PBX1(+) B-cell Acute Lymphoblastic Leukemia].0
350926532022MicroRNA gene methylation landscape in pediatric B-cell precursor acute lymphoblastic leukemia.0
203027702010[A clinical and laboratory study of TCF3-PBX1 positive adult acute lymphoblastic leukemia.].0
345974662022Clonal dynamics in pediatric B-cell precursor acute lymphoblastic leukemia with very early relapse.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
384071972024TCF3::PBX1 fusion pediatric B acute lymphoblastic leukemia in disguise behind the eyes - an unusual clinicopathologic presentation with hyperdiploid clone.0
238599042013Frequency of the ETV6-RUNX1, BCR-ABL1, TCF3-PBX1, and MLL-AFF1 fusion genes in Guatemalan pediatric acute lymphoblastic leukemia patients and their ethnic associations.0
173113192007Molecular cytogenetic characterization of TCF3 (E2A)/19p13.3 rearrangements in B-cell precursor acute lymphoblastic leukemia.0
340497152021Expression of BCL6 in paediatric B-cell acute lymphoblastic leukaemia and association with prognosis.0
333865962021The role of minimal residual disease in specific subtypes of pediatric acute lymphoblastic leukemia.0
276984472017Long-term outcome of 6-month maintenance chemotherapy for acute lymphoblastic leukemia in children.0
360442982023Clinical and Cytogenetic Characteristics of Children With Leukemia 20-Year Retrospective Study.0
318285952020Multiple heterogeneous bone invasions of B lymphoblastic lymphoma with the TCF3/PBX1 fusion gene: a case report.0
375942942023BRD4 PROTAC degrader MZ1 exhibits anti-B-cell acute lymphoblastic leukemia effects via targeting CCND3.0
365506422022Cytogenetic Profile Of Acute Lymphoblastic Leukaemia Patients And Its Association With Induction Remission Status.0
353444692022Adult acute lymphoblastic leukemia in a resource-constrained setting: outcomes after expansion of genetic evaluation.0

Article Bibliography

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

Summary

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

Note

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.

Citation

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