t(2;9)(p24;p13) PAX5/KIDINS220

2018-11-01   Tatiana Gindina 

1.R.M. Gorbacheva Memorial Institute of Children Oncology, Hematology and Transplantation at Pavlov First Saint-Petersburg State Medical University, Saint-Petersburg, Russian Federation / e-mail: tatgindina@gmail.com

Abstract

Review on t(2;9)(p24;p13), with data on the genes involved

Clinics and Pathology

Disease

B acute lymphoblastic leukemia

Phenotype stem cell origin

Immunophenotyping revealed that the leukemic blasts were positive for CD10, CD19, CD34, CD58, CD66c, CD38, CD79a, and HLA-DR.

Epidemiology

Only one case to date: a 7-year-old boy (Sakamoto et al, 2016).

Treatment

The patient achieved first complete remission under the extremely high-risk protocol (JACLS ALL-02), he underwent allogeneic HSCT due to a poor response to initial induction therapy. However, the patient relapsed and died in 5 years after the initial diagnosis (Sakamoto et al. ,2017).

Genes Involved and Proteins

Gene name
Location
2p24
Note
Kinase D-interacting substrate of 220 kDa.
Protein description
KIDINS220 gene encodes a transmembrane protein that is a mediator of multiple receptor signaling pathways, interacts with both T- and B-cell receptors, and is necessary for sustained extracellular signal-regulated kinase (ERK) signaling.
Gene name
Location
9p13
Protein description
PAX5 gene encodes a member of the paired box family of transcription factors. PAX5 is the B-cell lineage specific activator protein that is expressed at early stages of B-cell differentiation. PAX5 rearrangements induce a differentiation block in B lymphocytes.

Result of the Chromosomal Anomaly

Description

PAX5/KIDINS220

Transcript

Nucleotide sequence analyses revealed that PAX5 exon 7 was fused in-frame to KIDINS220 exon 20.
Atlas Image
Structure of the PAX5/KIDNS220 fusion protein. PD, paired domain; OP, octapeptide domain; HD, homeodomain; TAD, transactivation domain; ID- inhibitory domain; Pro, proline-rich domain; SAM, sterile alpha motif domain; KIM, kinesin light chain-interacting motif; PDZ, PDZ-binding motif; Ank, ankyrin repeat; TM, transmembrane region.

Description

The PAX5 protein is fused in-frame to KIDINS220 at amino acids 306 and 871, respectively, resulting in the preservation of the N-terminal region of PAX5, including the DNA-binding domain, and the C-terminal region of KIDINS220, including several protein-protein interaction domains (Sakamoto et al., 2017). The PAX5/KIDINS220 fusion protein preserves the DNA-binding domain of PAX5 and growth promotion activities of KIDINS220.

Oncogenesis

The PAX5/KIDINS220 fusion protein plays a dual role in leukemogenesis: first, the fusion protein likely induces a block in the differentiation of B lymphocytes by inhibition of wild-type PAX5 function; second, it possibly enhances ERK signaling pathway activation through KIDINS220, resulting in increased proliferation and a survival advantage for leukemic cells. Functional studies need to be performed to determine the precise function of PAX5/KIDINS220 fusion (Sakamoto et al., 2017).

Bibliography

Pubmed IDLast YearTitleAuthors
278701512017Ph-like acute lymphoblastic leukemia with a novel PAX5-KIDINS220 fusion transcript.Sakamoto K et al

Summary

Fusion gene

PAX5/KIDINS220

Citation

Tatiana Gindina

t(2;9)(p24;p13) PAX5/KIDINS220

Atlas Genet Cytogenet Oncol Haematol. 2018-11-01

Online version: http://atlasgeneticsoncology.org/haematological/1805/t(2;9)(p24;p13)

External Links