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?)

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

External Links