t(17;19)(q22;p13) TCF3/HLF

1999-05-01   Franck Viguié  

Clinics and Pathology

Disease

acute lymphoblastic leukemia (ALL)

Phenotype stem cell origin

precursor-B cell immunophenotype; characteristic expression of surface markers CD10, CD19, TdT, HLA-DR

Epidemiology

less than 1% of ALL cases; 1% of childhood B-ALL ; sex ratio 1M/1F; more frequent in children

Clinics

frequent disseminated intravascular coagulation at diagnosis (not observed in ALL with other translocations)

Cytology

pro-B lymphocytes

Prognosis

poor; no response to intensive chemotherapy and short survival

Cytogenetics

Cytogenetics morphological

presents usually as a balanced translocation t(17;19)(q22;p13); in some cases, only the der(19)t(17;19) is observed, but not the der(17); the same unbalanced form occurs in the closely related t(1;19)

Additional anomalies

found in appproximately 50% of cases

Variants

the translocation t(1;19)(q23;p13) and the t(17;19)(q22;p13) can be considered as variants of each other

Genes Involved and Proteins

Gene name
HLF (hepatic leukemia factor)
Location
17q22
Atlas Image
Protein description
basic leucine zipper (bZIP) transcription factor; normally expressed in hepatocytes and, at lower level, in lung and renal cells but not in hematopoietic cells
Gene name
TCF3 (transcription factor 3 (E2A immunoglobulin enhancer binding factors E12/E47))
Location
19p13.3
Atlas Image
Protein description
E2A encodes the basic helix loop helix (bHLH) transcription factors E12 and E47; expressed in most cell types

Result of the Chromosomal Anomaly

Atlas Image

Description

fusion gene E2A-HLF on der(19); two types of genomic rearrangements: type 1 results from a crossover between E2A intron 13 and HLF intron 3, type 2 from a crossover between E2A intron 12 and HLF intron 3- t(17;19) type I: 5 E2A exons 1 to 13 cryptic exon formed by E2A intron/HLF intron sequences to reestablish a reading frame HLF exon 4 in 3- t(17;19) type II: 5 E2A exons 1 to 12 HLF exon 4 in 3

Transcript

expression of two mRNAs of 4.4 and 4.8kb with the same coding sequence

Detection protocole

RT-PCR

Description

the fusion results in linking the amino-terminal transactivation domains 1 and 2 of E2A to the carboxy-terminal leucine zipper and basic domain of HLF; the minor structural difference induced in both types of proteins does not appear to have any functional consequence

Oncogenesis

the fusion gene encodes a chimeric transcription factor E2A-HLF with altered DNA binding affinity compared with native HLF; it functions as an antiapoptotic transcription factor in leukemic cell transformation; when E2A-HLF protein was introduced into murine pro-B lymphocytes, it reverted both interleukin-3-dependent and p53-mediated apoptosis; E2A-HLF could act by regulating expression of downstream target genes : possible activation of target genes normally repressed in B-cell precursors by another bZIP protein gene, E4BP4 (dominant negative effect by heterodimerization with endogenous proteins?)

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
281227422017Ex vivo drug response profiling detects recurrent sensitivity patterns in drug-resistant acute lymphoblastic leukemia.76
270332382016New and emerging prognostic and predictive genetic biomarkers in B-cell precursor acute lymphoblastic leukemia.58
317356272019The Leukemogenic TCF3-HLF Complex Rewires Enhancers Driving Cellular Identity and Self-Renewal Conferring EP300 Vulnerability.15
307654702019Durable remissions in TCF3-HLF positive acute lymphoblastic leukemia with blinatumomab and stem cell transplantation.15
310287442019Targeting ADP-ribosylation by PARP inhibitors in acute myeloid leukaemia and related disorders.12
278949582017Poly (ADP-ribose) polymerase inhibitors selectively induce cytotoxicity in TCF3-HLF-positive leukemic cells.10
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
231819812012A novel TCF3-HLF fusion transcript in acute lymphoblastic leukemia with a t(17;19)(q22;p13).4
323788102020High incidence of RAS pathway mutations among sentinel genetic lesions of Korean pediatric BCR-ABL1-like acute lymphoblastic leukemia.3
350656802022Targeting PARP proteins in acute leukemia: DNA damage response inhibition and therapeutic strategies.2
353284872022Resistance Mechanisms in Pediatric B-Cell Acute Lymphoblastic Leukemia.1
344601332022Cryptic TCF3 fusions in childhood leukemia: Detection by RNA sequencing.1
342334492021Aurora A kinase as a target for therapy in TCF3-HLF rearranged acute lymphoblastic leukemia.1
336402842021Successful Treatment of TCF3-HLF-positive Childhood B-ALL with Chimeric Antigen Receptor T-Cell Therapy.1
323914172020Targeting the oncogenic activity of TCF3-HLF in leukemia.1
310585562019The first case of elderly TCF3-HLF-positive B-cell 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
360018602022TCF3-HLF-Positive Acute Lymphoblastic Leukemia Resembling Burkitt Leukemia: Cell Morphologic and Immunophenotypic Findings.0
359070392022Clonal evolution in adult TCF3::HLF-positive acute lymphoblastic leukemia undergoing stem cell transplantation.0
348713732022Impact of high-risk cytogenetics on outcomes for children and young adults receiving CD19-directed CAR T-cell therapy.0
322453832020Comprehensive chromosomal aberrations in a case of a patient with TCF3-HLF-positive BCP-ALL.0
343653922020The Leukemia-Driving Fusion Protein TCF3-HLF Is Regulated by EP300.0
271833802016A t(17;19)(q22;p13.3) Involving TCF3, a t(1;9)(p13;p13), and a 5' IGH Deletion in a Case of Adult B-cell Acute Lymphoblastic Leukemia.0

Article Bibliography

Pubmed IDLast YearTitleAuthors
75185491994E2A/HLF fusion cDNAs and the use of RT-PCR for the detection of minimal residual disease in t(17;19)(q22;p13) acute lymphoblastic leukemia.Devaraj PE et al
86082071996Chromosomal translocations involving the E2A gene in acute lymphoblastic leukemia: clinical features and molecular pathogenesis.Hunger SP et al
87002281996Reversal of apoptosis by the leukaemia-associated E2A-HLF chimaeric transcription factor.Inaba T et al
13861621992Fusion of the leucine zipper gene HLF to the E2A gene in human acute B-lineage leukemia.Inaba T et al
90322681997Cell transformation mediated by homodimeric E2A-HLF transcription factors.Inukai T et al
20188381991New recurring chromosomal translocations in childhood acute lymphoblastic leukemia.Raimondi SC et al

Summary

Fusion gene

TCF3/HLF TCF3 (19p13.3) HLF (17q22) M t(17;19)(q22;p13)|TCF3/HLF TCF3 (19p13.3) HLF (17q22) TIC

Citation

Franck Viguié

t(17;19)(q22;p13) TCF3/HLF

Atlas Genet Cytogenet Oncol Haematol. 1999-05-01

Online version: http://atlasgeneticsoncology.org/haematological/1078/case-report-explorer/favicon/deep-insight-explorer/