| Written | 2018-11 | Tatiana Gindina |
| 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 |
| Keywords | Chromosome 2; Chromosome 9; |
| Identity |
| ICD-Topo | C420,C421,C424 |
| ICD-Morpho | 9811/3 B lymphoblastic leukaemia/lymphoma, NOS |
| Atlas_Id | 1805 |
| Clinics and Pathology |
| Disease | B acute lymphoblastic leukemia |
| Phenotype / cell stem 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). |
| Cytogenetics |
| Cytogenetics Morphological | G-banding analysis showed a normal karyotype. It is a cryptic translocation, not visible with conventional cytogenetics. |
| Genes involved and Proteins |
| Gene Name | KIDINS220 |
| Location | 2p24 |
| Note | Kinase D-interacting substrate of 220 kDa. |
| Protein | 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 | PAX5 |
| Location | 9p13 |
| Protein | 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. |
 | |
| 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). |
| To be noted |
| Additional cases are needed to delineate the epidemiology of this rare entity: you are welcome to submit a paper to our new Case Report section. |
| Bibliography |
| Ph-like acute lymphoblastic leukemia with a novel PAX5-KIDINS220 fusion transcript. |
| Sakamoto K, Imamura T, Kanayama T, Yano M, Asai D, Deguchi T, Hashii Y, Tanizawa A, Ohshima Y, Kiyokawa N, Horibe K, Sato A. |
| Genes, Chromosome Cancer. 2017; 56(4):278-284. |
| PMID 27870151 |
| Citation |
| This paper should be referenced as such : |
| Gindina T |
| t(2;9)(p24;p13) PAX5/KIDINS220; |
| Atlas Genet Cytogenet Oncol Haematol. in press |
| On line version : http://AtlasGeneticsOncology.org/Anomalies/t0209p24p13PAX5_KIDINS220ID1805.html |
| Translocations implicated (Data extracted from papers in the Atlas) |
| t(2;9)(p24;p13) PAX5/KIDINS220 | |
| External links |
| REVIEW articles | automatic search in PubMed |
| Last year articles | automatic search in PubMed |
| All articles | automatic search in PubMed |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Mon Mar 25 16:48:45 CET 2019 |
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