t(7;17)(q11;q21) GTF2I/RARA in APL

2014-11-01   Guang-Sen Zhang 

1.Department of Hematology/Institute of Molecular Hematology, The Second Xiang-Ya Hospital, Central South University, Changsha, Hunan, 410011, P.R of China; E-mail: zgsllzy@163.com


Review on t(7;17)(q11;q21) GTF2I/RARA in acute promyelocytic leukaemia, with data on clinics, and the genes involved.

Clinics and Pathology


Phenotype stem cell origin

HLA-DR-, CD34-, CD13+, CD33+, CD64+.


One case reported so far. A 35-year old male.


The patient exhibited leukocytosis and coagulopathy.
Atlas Image
Mophorlogy of GTF2I-RARA variant APL. Wright Giemsa staining. Image acquired at x1000 magnification.


The cytoplasm was occupied by densely packed coarse granules. The nuclei were relatively regular. Auer rods and fagot cells were absent. MPO staining is strongly positive.


ATRA in combination with anthracycline-based chemotherapy did not induce remission. Neither are conventional chemotherapy and ATRA in combination with arsenics. No morphology differentiation of blast cells was seen after ATRA treatment.


No remission was obtained after ATRA and conventional chemotherapy. The patient died of intracranial hemorrhage on day 143 without remission.





Cryptic translocation. FISH studies are needed to uncover the rearrangment.
Atlas Image
Metaphase fluorescence in situ hybridization (FISH). On the left, PML-RARA dual colour, dual-fusion translocation probes found RARA rearrangement. The RARA signals are shown in red, while PML signals are shown in green. Intact RARA and PML are shown as (r) and (p), while the split RARA signals are indicated as (s).In the middle, probes specific for the chromosome 7 centromere (GLP D7S486 probes, green) and 7q31 (CSP7 probes, red) confirmed the deletion of the long arm of one chromosome 7. On the right, the combined application of chromosome 7 probes and PML-RARA probes found that one split RARA was translocated to the truncated long arm of chromosome 7. Signal detection was carried out on metaphases according to the manufacturers protocols (Jinpujia, Beijing, China).

Genes Involved and Proteins

Gene name
GTF2I (general transcription factor IIi)
General transcription factor IIi
Protein description
GTF2I is a ubiquitously expressed phosphoprotein with broad roles in transcription and signal transduction involving growth factor signalling, cell cycle regulation, and transforming growth factor, beta 1(TGFB1) signalling, ER stress response pathway, calcium signalling, and immune signalling (Roy, 2012).
Gene name
RARA (Retinoic acid receptor, alpha)
Retinoic acid receptor alpha
Protein description
RARA is a nuclear retinoic acid receptor that regulates transcription in a ligand-dependent manner. This gene has been implicated in regulation of hemopoietic cells differentiation.

Result of the Chromosomal Anomaly


In-frame fusion of exon 6 of GTF2I to exon 3 of RARA


5GTF2I-3RARA. No reciprocal 5RARA-3GTF2I.

Detection protocole

Reverse transcript polymerase chain reaction.
Atlas Image
Schematic diagram of RARA, GTF2I and GTF2I-RARA fusion protein. A black line indicates the break point. DBD, DNA-binding domain; LBD +DD, ligand-binding domain and dimerization domain; LZ, leucine zipper; NLS, nuclear localization signal; BR, basic region; R1-R6, I-repeat domains.


The fusion transcript encodes a 598 amino acids chimera containing the 195 amino-terminal amino acids of GTF2I, including the N-terminal leucine zipper and the first I-repeat domain, and 403 carboxyl-terminal amino acids of RARA, including the DNA and ligand binding domains.

Expression localisation

Two patterns of GTF2I-RARA localization were observed: diffuse nuclear distribution with a micropunctate pattern, and aggregation in the cytoplasm as macrogranules.


GTF2I-RARA chimera possesses common features of APL related fusion proteins: the same RARA portion, the ability to self-associate, dominant-negative regulation of the retinoic acid response element, and aberrant subcellular localization.

Highly cited references

Pubmed IDYearTitleCitations
252847162015GTF2I-RARA is a novel fusion transcript in a t(7;17) variant of acute promyelocytic leukaemia with clinical resistance to retinoic acid.21
329079142021Gene of the month: GTF2I.4
309926912019RNF8 is responsible for ATRA resistance in variant acute promyelocytic leukemia with GTF2I/RARA fusion, and inhibition of the ubiquitin-proteasome pathway contributes to the reversion of ATRA resistance.4


Pubmed IDLast YearTitleAuthors
252847162015GTF2I-RARA is a novel fusion transcript in a t(7;17) variant of acute promyelocytic leukaemia with clinical resistance to retinoic acid.Li J et al
220376102012Biochemistry and biology of the inducible multifunctional transcription factor TFII-I: 10 years later.Roy AL et al


Atlas Image
G-banding karyotype of del(7q). No distinct chromosome tranlocation.


Guang-Sen Zhang

t(7;17)(q11;q21) GTF2I/RARA in APL

Atlas Genet Cytogenet Oncol Haematol. 2014-11-01

Online version: http://atlasgeneticsoncology.org/haematological/1711/t(7;17)(q11;q21)-gtf2i-rara-in-apl