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

Written1999-05Franck Viguié
Laboratoire de Cytogenetique - Service d'Hematologie Biologique, Hopital Hotel-Dieu - 75181 Paris Cedex 04, France

(Note : for Links provided by Atlas : click)

Identity

ICD-Topo C420,C421,C424 BLOOD, BONE MARROW, & HEMATOPOIETIC SYS
ICD-Morpho 9811/3 B lymphoblastic leukaemia/lymphoma, NOS
Atlas_Id 1078

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 NameHLF (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 NameTCF3 (transcription factor 3 (E2A immunoglobulin enhancer binding factors E12/E47))
Location 19p13.3
 
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?)
  

Bibliography

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
 
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
 
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
 
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
 
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
 
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
 

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 journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Anomalies/t1719ID1078.html


Other genes implicated (Data extracted from papers in the Atlas) [ 2 ]

Genes TCF3 HLF

Translocations implicated (Data extracted from papers in the Atlas)

 t(17;19)(q22;p13) TCF3/HLF

External links

TCF3 (19p13.3) HLF (17q22)

TCF3 (19p13.3) HLF (17q22)

Mitelman databaset(17;19)(q22;p13) [Case List]    t(17;19)(q22;p13) [Association List] Mitelman database (CGAP - NCBI)
arrayMapTopo ( C42) Morph ( 9811/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
 
Mitelman databaseTCF3/HLF [MCList]  TCF3 (19p13.3) HLF (17q22)
TICdbTCF3/HLF  TCF3 (19p13.3) HLF (17q22)
 
Disease databaset(17;19)(q22;p13) TCF3/HLF
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed


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