The TT Genotype of the <i>KIAA1524 rs2278911</i> Polymorphism Is Associated with Poor Prognosis in Multiple Myeloma

Background: The <i>KIAA1524</i> gene encodes an oncoprotein, CIP2A, which inhibits the phosphorylation of the Akt kinase B, stabilizes the c-Myc protein, and, through that, promotes cancerogenesis. An increase in CIP2A expression has been observed in numerous solid tumors and hematologic...

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Main Authors: Aneta Szudy-Szczyrek, Radosław Mlak, Marcin Mazurek, Tomasz Krajka, Sylwia Chocholska, Paulina Bitkowska, Marta Jutrzenka, Michał Szczyrek, Iwona Homa-Mlak, Andrzej Krajka, Teresa Małecka-Massalska, Marek Hus
Format: Article
Language:English
Published: MDPI AG 2023-03-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/12/7/1029
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Summary:Background: The <i>KIAA1524</i> gene encodes an oncoprotein, CIP2A, which inhibits the phosphorylation of the Akt kinase B, stabilizes the c-Myc protein, and, through that, promotes cancerogenesis. An increase in CIP2A expression has been observed in numerous solid tumors and hematologic malignancies, including multiple myeloma (MM). The aim of our study was to evaluate the clinical impact of the functional single nucleotide polymorphisms (SNP) of the <i>KIAA1524</i> gene (rs2278911, 686C > T) in MM patients. Methods: The study group consisted of 128 patients with de novo MM. EDTA venous blood samples were collected prior to the treatment. The SNPs were analyzed by Real-Time PCR with the use of specific Taqman probes. Results: Multivariable analysis revealed that variables independently associated with shorter progression-free survival (PFS) included thrombocytopenia, <i>delTP53</i> and <i>IGH/CCND1</i> translocation and the TT genotype of the <i>KIAA1524</i> gene (686C > T) (median PFS: 6 vs. 25 months; HR = 7.18). On the other hand, autologous haematopoietic stem cell transplantation (AHSCT) was related to a lower risk of early disease progression. Moreover, light chain disease, International Staging System (ISS) 3, poor performance status, hypoalbuminemia, <i>IGH/FGFR3</i> translocation and the TT genotype of the <i>KIAA1524</i> gene (686C > T) were independent prognostic factors associated with shorter overall survival (OS) (median OS: 8 vs. 45 months; HR = 7.08). Conclusion: The evaluation of the SNP 686C > T of the <i>KIAA1524</i> gene could be used as a diagnostic tool in MM patients at risk of early disease progression and death.
ISSN:2073-4409