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.


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)-tcf3-pbx1

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

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