Atlas of Genetics and Cytogenetics in Oncology and Haematology

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t(15;17)(q24;q21) PML/RARA


ICD-Morpho "9866/3 Acute promyelocytic leuk.,t(15;17)(q22;q11-12)"
Atlas_Id 1035
Note The translocation, known as t(15;17)(q22;q21) or t(15;17)(q22;q12), has be renamed t(15;17)(q24;q21), since PML sits in 15q24, and RARA in 17q21
  t(15;17)(q24;q21) G- banding (left) - 2 top left: Courtesy Jean-Luc Lai and Alain Vanderhaegen, 2 bottom left: Courtesy Roland Berger ; R-banding (right) - top: Editor, middle: Courtesy Christiane Charrin, bottom: Courtesy Roland Berger .

Clinics and Pathology

Disease M3 AML (de novo); a very few cases of t(15;17) in therapy-related leukaemia (t-AML) have been reported.
Phenotype / cell stem origin t(15;17) is quasi pathognomonic of M3 AML (acute promyelocytic leukemia, or APL).
Epidemiology found in 10% of adult AML; annual incidence: 1/106, similar to the incidence of the t(8;21) ; any age, but frequent in the young adult; sex ratio 1M/1F.
Clinics WBC and platelets may be lower than in other AML; coagulopathy
Cytology large cells with myeloperoxidase positive cytoplasmic granulations (microgranular forms are called variant M3 AML, and are often hyperleucocytic); bundles of Auer rods.
t(15;17)(q24;21) is associated conbsistently with AML M3. This chromosomal abnormality first appeared to be confined to the characteristic or morphologically typical M3 AML or "hypergranular promyelocytic leukemia", defined by bone marrow replacement with highly granulated blast cells. The nuclear size and shape is irregular and highly variable; they are often kidney-shaped or bilobed. The cytoplasm is completely occupied by densely packed or even coalescent large granules, staining bright pink, red or purple by MGG. In some cells the cytoplasm is filled with fine dust-like granules. Characteristic cells containing bundles of Auer rods ("faggot cells") randomly distributed in the cytoplasm, although frequent, are not present in all cases. Auer rods in M3 are usually larger than in other AML and they may have a characteristic morphology at the ultrastructural level. In some cases, the cytoplasmic granules are so large and/or numerous that they totally obscure the cell, rendering the nuclear cytoplasmic limit indistinct. In M3 AML, MPO is always strongly positive in all blast cells, with the reaction product covering the whole cytoplasm and often the nucleus too - Text and iconography Courtesy Georges Flandrin 2001.
Treatment one of the rare leukaemia where treatment is an emergency, as intra vascular coagulation is prominent, causing a high rate (10 to 40%) of early mortality, mainly due to cerebral haemorrhage; with the recent differentiation therapy using all trans-retinoic acid (with combined chemotherapy), CR is obtained in 80-90% of cases; this is the only cancer which, to date, can be treated by differentiation therapy.
Prognosis early death rate still at 15-20%; combination of retinoic acid and chemotherapy prolonged survival significantly: survival at 1 yr and at 3 yrs are stable at 70%, instead of a 30 to 40 % 3 yr survival previously.


  PMLRARA in t(15;17)(q24;q21) - Courtesy Maria no Rocchi, Resources for Molecular Cytogenetics.
Cytogenetics Morphological although primary anomaly in most cases, t(15;17) can also occur in rare occurrences at acutisation (of promyelocytic type, of course) of a CML with the usual t(9;22).
Additional anomalies +8 in 1/3 of cases; del (7q); del(9q) rare.
Variants 1- true variants, i.e. three way complex t(15;Var;17) exist; they demonstrated that the crucial event lies on der(15), which receives the end part of chromosome 17. 2- related translocations, rarely observed, involve a commun breakpoint in 17q21, within RARa, fused with different partners, in: t(11;17)(q23;q21), fusion with PLZF, t(5;17)(q32;q12), fusion with NPM1, and t(11;17)(q13;q21), fusion with NUMA.

Genes involved and Proteins

Gene Name PML
Location 15q24
Dna / Rna numerous splices in 3'
Protein nuclear protein; contains zinc fingers and a leucine zipper; transcription factor
Gene Name RARA
Location 17q12-21
Protein wide expression; nuclear receptor; binds specific DNA sequences: HRE (hormone response elements); ligand and dimerization domain; role in growth and differentiation.

Result of the chromosomal anomaly

Hybrid gene
  PML and RARA breakpoints in the t(15;17) / 5' PML - 3' RARA fusion gene - Courtesy Hossein Mossafa.
Description variable breakpoint in PML between intron 3 and exon 7a; constant breakpoint in intron 2 of RARa.
Transcript 5' PML -3' RARa transcript is found in all cases, and 5' RARa - 3' PML transcript is detected in 2/3 of cases.
Fusion Protein
Description variable, as breakpoints in PML are variable; e.g.: 932 amino acids; 103 kDa; N-term PML, with the DNA binding and the dimerization domains fused to most of RARa with the DNA and retinoid binding regions.
Oncogenesis abnormal retinoic acid receptor with a dominant effect over RARa, antagonizing differentiation.

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


Translocations implicated (Data extracted from papers in the Atlas)

 t(15;17)(q24;q21) PML/RARA

External links

Mitelman databaset(15;17)(q24;q21) [Case List]    t(15;17)(q24;q21) [Association List] Mitelman database (CGAP - NCBI)
COSMICHisto = - Site = haematopoietic_and_lymphoid_tissue (COSMIC)
arrayMapTopo ( C42) Morph ( 9866/3) - arrayMap (Zurich)


Molecular analysis of acute promyelocytic leukemia breakpoint cluster region on chromosome 17.
Borrow J, Goddard AD, Sheer D, Solomon E
Science (New York, N.Y.). 1990 ; 249 (4976) : 1577-1580.
PMID 2218500
The t(15;17) translocation of acute promyelocytic leukaemia fuses the retinoic acid receptor alpha gene to a novel transcribed locus.
de Thˆ© H, Chomienne C, Lanotte M, Degos L, Dejean A
Nature. 1990 ; 347 (6293) : 558-561.
PMID 2170850
Translocation breakpoint of acute promyelocytic leukemia lies within the retinoic acid receptor alpha locus.
Alcalay M, Zangrilli D, Pandolfi PP, Longo L, Mencarelli A, Giacomucci A, Rocchi M, Biondi A, Rambaldi A, Lo Coco F
Proceedings of the National Academy of Sciences of the United States of America. 1991 ; 88 (5) : 1977-1981.
PMID 1848017
Cytogenetic studies in acute promyelocytic leukemia: a survey of secondary chromosomal abnormalities.
Berger R, Le Coniat M, Derrˆ© J, Vecchione D, Jonveaux P
Genes, chromosomes & cancer. 1991 ; 3 (5) : 332-337.
PMID 1797083
Genomic variability and alternative splicing generate multiple PML/RAR alpha transcripts that encode aberrant PML proteins and PML/RAR alpha isoforms in acute promyelocytic leukaemia.
Pandolfi PP, Alcalay M, Fagioli M, Zangrilli D, Mencarelli A, Diverio D, Biondi A, Lo Coco F, Rambaldi A, Grignani F
The EMBO journal. 1992 ; 11 (4) : 1397-1407.
PMID 1314166
Acute promyelocytic leukemia.
Warrell RP Jr, de Thˆ© H, Wang ZY, Degos L
The New England journal of medicine. 1993 ; 329 (3) : 177-189.
PMID 8515790
Treatment of newly diagnosed acute promyelocytic leukemia (APL) by all transretinoic acid (ATRA) combined with chemotherapy: The European experience. European APL Group.
Fenaux P, Chastang C, Chomienne C, Castaigne S, Sanz M, Link H, Lˆwenberg B, Fey M, Archim-Baud E, Degos L
Leukemia & lymphoma. 1995 ; 16 (5-6) : 431-437.
PMID 7787753
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed


Written04-1998Jean-Loup Huret and Christine Chomienne
Laboratoire de Biologie Cellulaire Hématopoïétique, EP-107 CNRS, Institut d'Hématologie, Hôpital Saint Louis, Centre Hayem, Paris, France


This paper should be referenced as such :
Huret, JL ; Chomienne, C
Atlas Genet Cytogenet Oncol Haematol. 1998;2(3):101-103.
Free journal version : [ pdf ]   [ DOI ]
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