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
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
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
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 ID | Year | Title | Citations |
|---|---|---|---|
| 35328487 | 2022 | Resistance Mechanisms in Pediatric B-Cell Acute Lymphoblastic Leukemia. | 186 |
| 35065680 | 2022 | Targeting PARP proteins in acute leukemia: DNA damage response inhibition and therapeutic strategies. | 172 |
| 27033238 | 2016 | New and emerging prognostic and predictive genetic biomarkers in B-cell precursor acute lymphoblastic leukemia. | 98 |
| 26214592 | 2015 | Genomics and drug profiling of fatal TCF3-HLF-positive acute lymphoblastic leukemia identifies recurrent mutation patterns and therapeutic options. | 85 |
| 34871373 | 2022 | Impact of high-risk cytogenetics on outcomes for children and young adults receiving CD19-directed CAR T-cell therapy. | 55 |
| 28122742 | 2017 | Ex vivo drug response profiling detects recurrent sensitivity patterns in drug-resistant acute lymphoblastic leukemia. | 55 |
| 31305009 | 2019 | Resistance of t(17;19)-acute lymphoblastic leukemia cell lines to multiagents in induction therapy. | 38 |
| 32378810 | 2020 | High incidence of RAS pathway mutations among sentinel genetic lesions of Korean pediatric BCR-ABL1-like acute lymphoblastic leukemia. | 30 |
| 39414614 | 2024 | [Clinical analysis of 7 cases of acute B cell lymphoblastic leukemia with t (17;19) (q21-22;p13)/TCF3-HLF fusion]. | 28 |
| 36553362 | 2022 | Peripheral Bone Relapse of Paediatric TCF3-HLF Positive Acute Lymphoblastic Leukaemia during Haematopoietic Stem Cell Transplantation: A Case Report. | 27 |
| 32245383 | 2020 | Comprehensive chromosomal aberrations in a case of a patient with TCF3-HLF-positive BCP-ALL. | 23 |
| 31575852 | 2019 | Characterization 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 |
| 36001860 | 2022 | TCF3-HLF-Positive Acute Lymphoblastic Leukemia Resembling Burkitt Leukemia: Cell Morphologic and Immunophenotypic Findings. | 16 |
| 38426288 | 2024 | Proteogenomic profiling uncovers differential therapeutic vulnerabilities between TCF3::PBX1 and TCF3::HLF translocated B-cell acute lymphoblastic leukemia. | 15 |
| 30765470 | 2019 | Durable remissions in TCF3-HLF positive acute lymphoblastic leukemia with blinatumomab and stem cell transplantation. | 15 |
| 34233449 | 2021 | Aurora A kinase as a target for therapy in TCF3-HLF rearranged acute lymphoblastic leukemia. | 15 |
| 32391417 | 2020 | Targeting the oncogenic activity of TCF3-HLF in leukemia. | 10 |
| 37392046 | 2023 | TCF3::HLF acute lymphoblastic leukemia: still challenging to cure thirty years later. | 5 |
| 29334255 | 2018 | NGS-based methylation profiling differentiates TCF3-HLF and TCF3-PBX1 positive B-cell acute lymphoblastic leukemia. | 0 |
| 31735627 | 2019 | The Leukemogenic TCF3-HLF Complex Rewires Enhancers Driving Cellular Identity and Self-Renewal Conferring EP300 Vulnerability. | 0 |
| 35907039 | 2022 | Clonal evolution in adult TCF3::HLF-positive acute lymphoblastic leukemia undergoing stem cell transplantation. | 0 |
| 33640284 | 2021 | Successful Treatment of TCF3-HLF-positive Childhood B-ALL with Chimeric Antigen Receptor T-Cell Therapy. | 0 |
| 39145779 | 2024 | CD19 CAR T-cell therapy in relapsed TCF3-HLF-positive B-cell acute lymphoblastic leukemia. | 0 |
| 37058324 | 2023 | TCF3 gene rearrangements in pediatric B-cell acute lymphoblastic leukemia-A single center experience. | 0 |
| 34460133 | 2022 | Cryptic TCF3 fusions in childhood leukemia: Detection by RNA sequencing. | 0 |
| 27894958 | 2017 | Poly (ADP-ribose) polymerase inhibitors selectively induce cytotoxicity in TCF3-HLF-positive leukemic cells. | 0 |
| 23181981 | 2012 | A novel TCF3-HLF fusion transcript in acute lymphoblastic leukemia with a t(17;19)(q22;p13). | 0 |
| 31028744 | 2019 | Targeting ADP-ribosylation by PARP inhibitors in acute myeloid leukaemia and related disorders. | 0 |
| 31058556 | 2019 | The first case of elderly TCF3-HLF-positive B-cell acute lymphoblastic leukemia. | 0 |
| 36162014 | 2023 | T-Cell-Replete Haploidentical Hematopoietic Stem Cell Transplantation for a Patient With Tcf3-Hlf-Positive Acute Lymphoblastic Leukemia Extramedullary Relapse After Unrelated Bone Marrow Transplantation. | 0 |
| 39911115 | 2025 | Update on long-term outcomes of a cohort of patients with TCF3::HLF positive acute lymphoblastic leukemia treated with blinatumomab and stem cell transplantation. | 0 |
| 27183380 | 2016 | A 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 |
| 40020210 | 2025 | Challenging Conventional Diagnostic Methods by Comprehensive Molecular Diagnostics: A Nationwide Prospective Comparison in Children With ALL. | 0 |
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 7518549 | 1994 | E2A/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 |
| 8608207 | 1996 | Chromosomal translocations involving the E2A gene in acute lymphoblastic leukemia: clinical features and molecular pathogenesis. | Hunger SP et al |
| 8700228 | 1996 | Reversal of apoptosis by the leukaemia-associated E2A-HLF chimaeric transcription factor. | Inaba T et al |
| 1386162 | 1992 | Fusion of the leucine zipper gene HLF to the E2A gene in human acute B-lineage leukemia. | Inaba T et al |
| 9032268 | 1997 | Cell transformation mediated by homodimeric E2A-HLF transcription factors. | Inukai T et al |
| 2018838 | 1991 | New 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/t(17
