t(5;17)(q35;q21)

Clinics and Pathology

Disease	acute non lymphocytic leukemia (ANLL)
Phenotype / cell stem origin	acute promyelocytic leukemia (ANLL-M3 according to the FAB classification)
Etiology	exceptional; only 2 well documented cases
Clinics	both patients were pediatric cases: F/2.5yrs, M/12yrs; disseminated intravascular coagulation at diagnosis in one case; remission obtained with chemotherapy and/or ATRA; first relapse at 7 and 5 months respectively
Cytology	hypergranular and hypogranular bilobed promyelocytes; absence of Auer rods; typical microspeckeled pattern with anti-RARa antibodies; terminal differentiation of blasts and promyelocytes in vitro with ATRA
Prognosis	probably unfavorable (both patients had a short term first relapse)

Cytogenetics

Probes	RARa probe commercially available coupled with PML probe in dual color kits; non commercialized probes for NPM, previously used for t(2;5)(p23;q35) of anaplastic large cell lymphoma (same breakpoint into NPM) = cosmid clones 13, 15-2 and 47C12 retained by der(5)
Additional anomalies	one of the two cases had complex additional abnormalities
Variants	t(15;17)(q22;q21) t(11;17)(q23;q21) t(11;17)(q13;q21)

Genes involved and Proteins

Gene Name	NPM1
Location	5q35
Protein	gene for the nucleolar phosphoprotein nucleophosmin; would participate in ribosome assembly

Gene Name	RARa
Location	17 q21
Protein	gene for the retinoic acid receptor alpha; the breakpoint lies within the second intron of the gene, as in t(15;17) and t(11;17) translocations

Result of the chromosomal anomaly

Hybrid gene

Description	two reciprocal fusion genes are generated: 5'-NPM + 3'- RARa on der(5) and 5'-RARa + 3'-NPM on der(17); both fusion genes are transcribed, the crucial one is NPM-RARa; two NPM-RARa chimeric cDNAs are generated, one short and one long differing from 129 bp, with corresponding transcripts of 2.3 and 2.4 kb (alternatively spliced transcripts); in one case, only the short NPM-RARa isoform could be detected; the 5' end of NPM-RARa cDNAs contains the first 442 bp of the NPM cDNA; the 3' end contains RARa sequences of exon 3 through the 3' end of RARa; a reciprocal RARa-NPM transcript is detected: RARa exons 1 and 2 are fused to 3' NPM downstream bp 443
Detection	nested RT-PCR

Fusion Protein

Description	two NPM-RARa proteins, of 563 and 520 amino acids, are encoded (MW 62 and 57 kDa); NPM-RARa fusion protein acts as a retinoic acid-responsive transcriptional activator: increase of activity in a concentration dependant manner

External links

Other database	t(5;17)(q35;q21)	Mitelman database (CGAP - NCBI)
Other database	t(5;17)(q35;q21)	CancerChromosomes (NCBI)

To be noted

Additional cases are needed to delineate the epidemiology of this rare entity: you are welcome to submit a paper to our new Case Report section.

Bibliography

A non-classical translocation involving 17q12 (retinoic acid receptor alpha) in acute promyelocytic leukemia (APML) with atypical features.

Corey SJ, Locker J, Oliveri DR, Shekhter-Levin S, Redner RL, Penchansky L, Gollin SM

Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1994 ; 8 (8) : 1350-1353.

PMID 8057672

Variant and masked translocations in acute promyelocytic leukemia.

Brunel V, Lafage-Pochitaloff M, Alcalay M, Pelicci PG, Birg F

Leukemia & lymphoma. 1996 ; 22 (3-4) : 221-228.

PMID 8819070

PML, PLZF and NPM genes in the molecular pathogenesis of acute promyelocytic leukemia.

Pandolfi PP

Haematologica. 1996 ; 81 (5) : 472-482.

PMID 8952164

The t(5;17) variant of acute promyelocytic leukemia expresses a nucleophosmin-retinoic acid receptor fusion.

Redner RL, Rush EA, Faas S, Rudert WA, Corey SJ

Blood. 1996 ; 87 (3) : 882-886.

PMID 8562957

Differentiation of t(5;17) variant acute promyelocytic leukemic blasts by all-trans retinoic acid.

Redner RL, Corey SJ, Rush EA

Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1997 ; 11 (7) : 1014-1016.

PMID 9204984

Distinct leukemia phenotypes in transgenic mice and different corepressor interactions generated by promyelocytic leukemia variant fusion genes PLZF-RARalpha and NPM-RARalpha.

Cheng GX, Zhu XH, Men XQ, Wang L, Huang QH, Jin XL, Xiong SM, Zhu J, Guo WM, Chen JQ, Xu SF, So E, Chan LC, Waxman S, Zelent A, Chen GQ, Dong S, Liu JX, Chen SJ

Proceedings of the National Academy of Sciences of the United States of America. 1999 ; 96 (11) : 6318-6323.

PMID 10339585

The pathogenesis of acute promyelocytic leukaemia: evaluation of the role of molecular diagnosis and monitoring in the management of the disease.

Grimwade D

British journal of haematology. 1999 ; 106 (3) : 591-613.

PMID 10468848

Deregulation of NPM and PLZF in a variant t(5;17) case of acute promyelocytic leukemia.

Hummel JL, Wells RA, Dubˆ© ID, Licht JD, Kamel-Reid S

Oncogene. 1999 ; 18 (3) : 633-641.

PMID 9989813

Contributor(s)

Written	03-2000	Franck Vigué

Citation

This paper should be referenced as such :

Viguié F . t(5;17)(q35;q21). Atlas Genet Cytogenet Oncol Haematol. March 2000 . URL : http://AtlasGeneticsOncology.org/Genes/t517ID1081.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology

indexed on : Mon Jul 14 16:33:57 2008

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