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

Clinics and Pathology

Disease acute lymphoblastic leukemia (ALL)
Phenotype / cell stem 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 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 E2A
Location 19p13
 
Protein E2A encodes the basic helix loop helix (bHLH) transcription factors E12 and E47; expressed in most cell types

Result of the chromosomal anomaly

Hybrid gene
 
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 RT-PCR
  
Fusion Protein
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?)
  

Other genes implicated (Data extracted from papers in the Atlas)

Genes TCF3 HLF

Translocations implicated (Data extracted from papers in the Atlas)

 t(17;19)(q22;p13) TCF3/HLF

External links

Mitelman database
t(17;19)(q22;p13) - Mitelman database (CGAP - NCBI)

Bibliography

Chromosomal translocations involving the E2A gene in acute lymphoblastic leukemia: clinical features and molecular pathogenesis.
Hunger SP
Blood. 1996 ; 87 (4) : 1211-1224.
PMID 8608207
 
New recurring chromosomal translocations in childhood acute lymphoblastic leukemia.
Raimondi SC, Privitera E, Williams DL, Look AT, Behm F, Rivera GK, Crist WM, Pui CH
Blood. 1991 ; 77 (9) : 2016-2022.
PMID 2018838
 
Fusion of the leucine zipper gene HLF to the E2A gene in human acute B-lineage leukemia.
Inaba T, Roberts WM, Shapiro LH, Jolly KW, Raimondi SC, Smith SD, Look AT
Science (New York, N.Y.). 1992 ; 257 (5069) : 531-534.
PMID 1386162
 
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, Foroni L, Sekhar M, Butler T, Wright F, Mehta A, Samson D, Prentice HG, Hoffbrand AV, Secker-Walker LM
Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1994 ; 8 (7) : 1131-1138.
PMID 7518549
 
Reversal of apoptosis by the leukaemia-associated E2A-HLF chimaeric transcription factor.
Inaba T, Inukai T, Yoshihara T, Seyschab H, Ashmun RA, Canman CE, Laken SJ, Kastan MB, Look AT
Nature. 1996 ; 382 (6591) : 541-544.
PMID 8700228
 
Cell transformation mediated by homodimeric E2A-HLF transcription factors.
Inukai T, Inaba T, Yoshihara T, Look AT
Molecular and cellular biology. 1997 ; 17 (3) : 1417-1424.
PMID 9032268
 
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed

Contributor(s)

Written05-1999Franck Viguié

Citation

This paper should be referenced as such :
Viguié, F
t(17;19)(q22;p13)
Atlas Genet Cytogenet Oncol Haematol. 1999;3(2):93-94.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Anomalies/t1719ID1078.html

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indexed on : Thu Sep 25 15:37:04 CEST 2014


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