t(17;19)(q22;p13)

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t(17;19)(q22;p13)

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?)

External links

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

Other database t(17;19)(q22;p13) CancerChromosomes (NCBI)

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

Contributor(s)

Written 05-1999 Franck Viguié

Citation

This paper should be referenced as such :
Viguié F . t(17;19)(q22;p13). Atlas Genet Cytogenet Oncol Haematol. May 1999 .
URL : http://AtlasGeneticsOncology.org/Genes/t1719ID1078.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Wed Sep 24 21:07:38 2008

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For comments and suggestions or contributions, please contact us

j.l.huret@chu-poitiers.fr.

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 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

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



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

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?)