t(2;9)(q12;q34) RANBP2/ABL1

2015-12-01   Marc De Braekeleer , Nadia Guéganic , Alexandra Schifferli , Joëlle Tchinda. 

1.Cytogenetics Laboratory, Faculty of Medicine, University of Brest, France marc.debraekeleer@univ-brest.fr (MdeB, NG)) Department of Hematology/Oncology, University Childrens Hospital Basel, Switzerland (AS) University Childrens Hospital Zurich, Switzerland (JT).
2.Cytogenetics Laboratory, Faculty of Medicine, University of Brest, France marc.debraekeleer@univ-brest.fr (MdeB, NG)) Department of Hematology/Oncology, University Children s Hospital Basel, Switzerland (AS) University Children s Hospital Zurich, Switzerland (JT).


Review on t(2;9)(q12;q34), with data on clinics, and the genes involved.

Clinics and Pathology


Pre-B acute lymphoblastic leukemia


Two cases reported: a 15year-old male (Roberts et al., 2012; Roberts et al., 2014) and a 21-month girl (Braekeleer et al., 2015).


Alive 23 months after diagnosis in complete remission for one case, unknown for the other.



The t(2;9)(q12;q34)involves the RANBP2 and ABL1 genes. This fusion was first identified by RNA-sequencing in a boy with B-cell ALL (Roberts et al., 2012).

Cytogenetics morphological

t(2;9)(q12;q34) is identified by banding cytogenetics.

Cytogenetics molecular

FISH with a BCR-ABL probe showed 3 ABL signals. To determine the position of the breakpoints on chromosome 2, BACs located in bands 2q12.1 to 2q14.2 were used as probes in FISH experiments. A split signal on der(2) and der(9) was found with RP11-622D1, RP11-347H10, RP11-259O12, RP11-348G16 and RP11-953L12. These BAC clones overlap the RANBP2 gene and allow refinement of the breakpoint to a 25kb region covering the 5 end and the first three exons of RANBP2 (figure BAC).
Atlas Image
FISH with BACs RP11-953L12 (spectrum green, located in 2q12 and containing RANBP2) and RP11-83J21 (spectrum orange, located in 9q34 and containing the 3 part of ABL1) and CEP9 (in aqua) showing one fusion signal on der(2). No fusion is detected on der(9) because RP11-83J21 does not cover the 5 part of ABL1.

Genes Involved and Proteins

Gene name
RANBP2 (RAN binding protein 2)
Dna rna description
The RANBP2 (alias NUP358) gene contains 31 exons, spanning 66 kb. One major transcript with several alternative splicing variants is known.
Protein description
The protein has 3324 amino acids and is the largest component of nuclear pore complexes. It contains an N-terminal leucine-rich region, four RAN binding domains, eight zinc-finger motifs, a SUMO E3 ligase region and a C-terminal cyclophilin A-like domain. A detailed assessment of its functions is available elsewhere in the Atlas (Di Cesare E, Lavia P. RANBP2 (RAN binding protein 2. http://AtlasGeneticsOncology.org/Genes/RANBP2ID483.html).
Gene name
ABL1 (v-abl Abelson murine leukemia viral oncogene homolog 1)
Dna rna description
The ABL1 gene, spanning a 230kb region at band 9q34, includes the 5 alternative first exons 1b and 1a and ten common exons numbered from 2 to 11. Alternative splicing using exons 1b and 1a gives rise to mRNA of 7 and 6 kb, respectively.
Protein description
The ABL1 protein has three SRC homology (SH) domains called SH1, SH2 and SH3, of which SH1 that has tyrosine kinase function. The SH2 and SH3 domains are involved in protein-protein interactions, which regulate the tyrosine kinase activity; they are necessary for signal transduction function. The ABL1 protein has also three nuclear localization signal domains and three DNA binding regions and an F-actin binding domain.

Result of the Chromosomal Anomaly


The 3 region of ABL1 is translocated on the 5 region of RANBP2 on the der(2) and the 3 region of RANBP2 is translocated on the 5 region of ABL1 on der(9).

Detection protocole

FISH detection.


The fusion protein retains the leucine-rich domain, including a leucine zipper, located at the N-terminal of RANBP2 and the tyrosine kinase domain of the ABL1 protein.


The leucine-rich region of RANBP2 is predicted to mediate homo-oligomerization of the fusion protein, leading to the activation of the tyrosine kinase of ABL1.

Highly cited references

Pubmed IDYearTitleCitations
333900672021In-vitro modeling of TKI resistance in the high-risk B-cell acute lymphoblastic leukemia fusion gene RANBP2-ABL1 - implications for targeted therapy.0


Pubmed IDLast YearTitleAuthors
230417762013A translocation t(2;8)(q12;p11) fuses FGFR1 to a novel partner gene, RANBP2/NUP358, in a myeloproliferative/myelodysplastic neoplasm.Gervais C et al
244703792014Identification of RANBP2-ALK fusion in ALK positive diffuse large B-cell lymphoma.Lee SE et al
240348962013Inflammatory myofibroblastic tumor with RANBP2 and ALK gene rearrangement: a report of two cases and literature review.Li J et al
246132772014RANBP2-ALK fusion combined with monosomy 7 in acute myelomonocytic leukemia.Lim JH et al
126610112003Fusion of ALK to the Ran-binding protein 2 (RANBP2) gene in inflammatory myofibroblastic tumor.Ma Z et al
243075152014inv(2)(p23q13)/RAN-binding protein 2 (RANBP2)-ALK fusion gene in myeloid leukemia that developed in an elderly woman.Maesako Y et al
204281972010ALK fusion genes in children with atypical myeloproliferative leukemia.Röttgers S et al
252077662014Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia.Roberts KG et al


Fusion gene

RANBP2/ABL1 RANBP2 (2q12.3) ABL1 (9q34.12) M|RANBP2/ABL1 RANBP2 (2q12.3) ABL1 (9q34.12) M t(2;9)(q13;q34)
Atlas Image
GTG banding showing chromosomes 2 and 9 and the derivatives der(2) and der(9).


Marc De Braekeleer ; Nadia Guéganic ; Alexandra Schifferli ; Joëlle Tchinda.

t(2;9)(q12;q34) RANBP2/ABL1

Atlas Genet Cytogenet Oncol Haematol. 2015-12-01

Online version: http://atlasgeneticsoncology.org/haematological/1305/t(2;9)(q12;q34)