t(1;17)(q42;q21) IRF2BP2/RARA

2017-03-01   Adriana Zamecnikova 

1.Kuwait Cancer control Center, Department of Hematology, Kuwait; annadria@yahoo.com


Acute promyelocytic leukemia (APL) is characterized by the clonal expansion of myeloid precursors blocked at promyelocytic stage and the presence of t(15;17)(q24;q21) resulting in the fusion of retinoic acid receptor alpha (RARA) gene on 17q21.1 with promyelocytic leukemia (PML) gene at 15q24.1, and less frequently with other gene partners. Fusion between RARA and the interferon regulatory factor 2 binding protein 2 (IRF2BP2) genes is a rare variant translocation in APL.

Clinics and Pathology


Acute promyelocytic leukemia (APL; FAB type M3)


Only 3 cases to date, 2 females aged 19 and 68 years (Yin et al., 2015; Shimomura et al., 2016) and a 37-years old male patient (Jovanovic et al., 2017).


The 68?year?old female presented with no disseminated intravascular coagulation (DIC) Bone marrow showed marked hypercellularity with 36.8% promyelocytes with azurophilic granules and Auer rods. Immunophenotyping was positive for CD33, CD34, CD64, CD117 and HLA?DR (Shimomura et al., 2016).


The 19-year-old woman received all-trans retinoic acid (ATRA), arsenic trioxide and gemtuzumab ozogamicin and achieved complete remission but relapsed 10 months later (Yin et al., 2015). The other female patient received induction therapy with ATRA in comination with chemotherapy. After initial resistance she achieved hematological remission after re?induction therapy and remained in hematological remission for more than a year when she developed relapse and died 1 years later (Shimomura et al., 2016). The male patient was commenced on ATRA as a single agent and showed response to therapy revealing maturation of the leukemic blasts in bone marrows taken at day 7 and day 16 that was associated with normalization of the platelet count. Because real-time quantitative PCR showed persistent high level IRF2BP2/RARA fusion transcripts with ATRA as a single agent, chemotherapy was added that resulted in ongoing remission 32 months from diagnosis (Jovanovic et al., 2017).

Genes Involved and Proteins

Gene name
IRF2BP2 (interferon regulatory factor 2 binding protein 2)
Protein description
Belongs to a family of proteins that play a major role in the transcriptional regulation; acts as a transcriptional corepressor binding to the C-terminal repression domain of IRF2, a negative regulator of many interferon-responsive genes; its C-terminal RING-type zinc finger domain is sufficient for interaction with IRF2; this repression is not mediated by histone deacetylase activities.
Gene name
RARA (Retinoic acid receptor, alpha)
Protein description
Nuclear retinoic acid receptor; belongs to the large family of ligand responsive gene regulatory proteins, function as heterodimers with retinoid X receptors.

Result of the Chromosomal Anomaly


5 IRF2BP2 - 3 RARA.
In the case reported by Yin et al., 2015, breakpoints within IRF2BP2 exon 2 and RARA intron 2 were detected with breakpoints at positions 1687 bp in IRF2BP2 and 41620 bp in RARA. Through alternative splicing, 2 types of fusion transcripts between exon 1B of IRF2BP2 and exon 3 of RARA that resulted in an mRNA transcript 48 bp longer than variant 2 were found in a patient described by Shimomura et al., 2016. In the recently described case, fusion of exon 1 of IRF2BP2 to exon 3 of RARA was found (Jovanovic et al., 2017).


The N terminal part of the fusion protein originates from IRF2BP2 harbouring a zinc finger motif which may bind DNA and the C terminal part contains regions mediating DNA binding, ligand binding and RXR heterodimerization (Shimomura et al., 2015; Jovanovic et al., 2017).


The cryptic IRF2BP2/RARA fusion shows a similar breakpoint within the RARA gene as in PML-RARA and variant RARA fusions, thus retaining DNA binding, RXR heterodimerization, ligand binding, and co-repressor and co-activator interaction functions of RARA. The IRF2BP2/RARA fusion protein is likely the central leukemia-initiating event in APL patients by transforming hematopoietic stem/progenitor cells. In co-immunoprecipitation assays, IRF2BP2/RARA had the capacity to self-associate and behaved similarly to PML/RARA, inducing repression at retinoid response elements (Jovanovic et al., 2017).

Highly cited references

Pubmed IDYearTitleCitations
255837662015Identification of a novel fusion gene, IRF2BP2-RARA, in acute promyelocytic leukemia.22
271936002016New variant of acute promyelocytic leukemia with IRF2BP2-RARA fusion.13
278724982017The cryptic IRF2BP2-RARA fusion transforms hematopoietic stem/progenitor cells and induces retinoid-sensitive acute promyelocytic leukemia.12
293500802018IRF2BP2-RARA t(1;17)(q42.3;q21.2) APL blasts differentiate in response to all-trans retinoic acid.11
314475642019A rare case of acute promyelocytic leukemia with IRF2BP2-RARA fusion; and literature review.8
339579992021Current views on the genetic landscape and management of variant acute promyelocytic leukemia.5
326571802020Acute promyelocytic leukemia (APL) with an IRF2BP2-RARA fusion transcript: an aggressive APL variant.2
357040832022The rare IRF2BP2-RARA fusion in acute promyelocytic leukemia.0


Pubmed IDLast YearTitleAuthors
278724982017The cryptic IRF2BP2-RARA fusion transforms hematopoietic stem/progenitor cells and induces retinoid-sensitive acute promyelocytic leukemia.Jovanovic JV et al
271936002016New variant of acute promyelocytic leukemia with IRF2BP2-RARA fusion.Shimomura Y et al
255837662015Identification of a novel fusion gene, IRF2BP2-RARA, in acute promyelocytic leukemia.Yin CC et al


Fusion gene



Adriana Zamecnikova

t(1;17)(q42;q21) IRF2BP2/RARA

Atlas Genet Cytogenet Oncol Haematol. 2017-03-01

Online version: http://atlasgeneticsoncology.org/haematological/1603/t(1;17)(q42;q21)