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t(5;17)(q35;q21) NPM1/RARA

Written2000-03Franck Vigué
Laboratoire de Cytogenetique - Service d'Hematologie Biologique, Hopital Hotel-Dieu - 75181 Paris Cedex 04, France

(Note : for Links provided by Atlas : click)


ICD-Morpho 9861/3 AML with mutated NPM1; AML with mutated CEBPA; Acute myeloid leukaemia, NOS
Atlas_Id 1081

Clinics and Pathology

Disease acute myeloid leukemia (AML)
Phenotype / cell stem origin acute promyelocytic leukemia (AML-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)


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

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.


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
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
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
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, Dubé ID, Licht JD, Kamel-Reid S
Oncogene. 1999 ; 18 (3) : 633-641.
PMID 9989813
PML, PLZF and NPM genes in the molecular pathogenesis of acute promyelocytic leukemia.
Pandolfi PP
Haematologica. 1996 ; 81 (5) : 472-482.
PMID 8952164
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
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


This paper should be referenced as such :
Viguié, F
Atlas Genet Cytogenet Oncol Haematol. 2000;4(2):72-73.
Free journal version : [ pdf ]   [ DOI ]
On line version :

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


Translocations implicated (Data extracted from papers in the Atlas)

 t(5;17)(q35;q21) NPM1/RARA

External links

NPM1 (5q35.1) RARA (17q21.2)

NPM1 (5q35.1) RARA (17q21.2)

Mitelman databaset(5;17)(q35;q21) [Case List]    t(5;17)(q35;q21) [Association List] Mitelman database (CGAP - NCBI)
arrayMapTopo ( C42) Morph ( 9861/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
Mitelman databaseNPM1/RARA [MCList]  NPM1 (5q35.1) RARA (17q21.2)
TICdbNPM1/RARA  NPM1 (5q35.1) RARA (17q21.2)
Disease databaset(5;17)(q35;q21) NPM1/RARA
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed

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