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CASC5 Gene Expression Changes Correlate with Targeted Mutations in Leukemia

  • MOLECULAR CELL BIOLOGY
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Abstract

Dysfunction of genes that control mitosis and are responsible for the correct segregation of sister chromatids in anaphase is often accompanied by aneuploidy, which is frequently detected in leukemia. One of the components of the kinetochore complex, namely, the AF15q14/KNL1/CASC5 protein, is an important factor ensuring the correct binding of the pericentromeric region of chromosomes with the spindle microtubules. As shown recently, in some leukemias, the gene of this protein can be involved in the generation of the chromosomal translocation t(11;15)(q23;q14) or a variant of the chimeric MLL-AF15Q14 oncogene, which serves as a biomarker of poor prognosis. Despite the implication of mRNA of the CASC5 gene in oncogenesis of solid tumors, expression of this gene in hematopoietic neoplasms has not been studied. We analyzed expression levels of the CASC5 gene and the nearest regulatory genes, including WT1, APOBEC3A (A3A), and N-MYC. A pronounced decrease in CASC5 expression in bone marrow cells of primary leukemia patients compared with healthy donors was found. It was also shown that reduced expression of the CASC5 gene correlates with the detection of targeted mutations in patients composed two prognostic subgroups (favorable, unfavorable) with a significance level (p <0.05). It was noted that the change in the expression level of the CASC5 gene in acute myeloid leukemia is associated with overexpression of the genes WT1, A3A, and in some cases N-MYC and SPT16, which is consistent with the resistance to chemotherapy and leukemia progression. However, the question of which regulatory gene initiates leukemogenesis remains open.

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  1. Research Institute of Oncology and Hematology, Almazov National Medical Research Center, 197341, St. Petersburg, Russia

    K. V. Bogdanov, O. V. Merzlikina, Y. V. Mirolyubova, L. L. Girshova, E. G. Lomaia & A. Y. Zaritskey

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  1. K. V. Bogdanov
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  2. O. V. Merzlikina
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  3. Y. V. Mirolyubova
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  4. L. L. Girshova
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Statement of compliance with standards of research involving humans as subjects. All procedures performed in the present study were in accordance with the ethical standards of the institutional research ethics committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all patients and healthy donors involved in the study.

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Translated by D. Novikova, K. Bogdanov

Abbreviations: B-ALL, B-cell acute lymphoblastic leukemia; T‑ALL, T-cell acute lymphoblastic leukemia; MDS, myelodysplastic syndrome; AML, acute myeloid leukemia; CML, chronic myeloid leukemia.

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Bogdanov, K.V., Merzlikina, O.V., Mirolyubova, Y.V. et al. CASC5 Gene Expression Changes Correlate with Targeted Mutations in Leukemia. Mol Biol 55, 121–132 (2021). https://doi.org/10.1134/S0026893321010027

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