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

• Published in: Cells (Basel, Switzerland) Switzerland), 2023-03, Vol.12 (7), p.1029
• Main Authors: Szudy-Szczyrek, Aneta, Mlak, Radosław, Mazurek, Marcin, Krajka, Tomasz, Chocholska, Sylwia, Bitkowska, Paulina, Jutrzenka, Marta, Szczyrek, Michał, Homa-Mlak, Iwona, Krajka, Andrzej, Małecka-Massalska, Teresa, Hus, Marek
• Format: Article
• Language: English
• Subjects: AKT protein; Bone marrow; c-Myc protein; Chromosomes; CIP2A; Disease Progression; Disease-Free Survival; Fibroblast growth factor receptors; Gene amplification; Gene expression; Gene polymorphism; Genotype; Growth factors; Heavy chains; Hematopoietic Stem Cell Transplantation; Hematopoietic stem cells; Humans; Immunoglobulins; Kinases; Malignancy; Medical prognosis; molecular biomarkers; Multiple myeloma; Multiple Myeloma - diagnosis; Multiple Myeloma - genetics; Multiple Myeloma - therapy; Mutation; MYC; Myc protein; Patients; Phosphorylation; Plasma; Polymorphism; prognosis; Proteins; Single-nucleotide polymorphism; Solid tumors; Stem cell transplantation; Thermal cycling; Thrombocytopenia
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells12071029

The 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 gene (rs2278911, 686C > T) in MM patients. 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. Multivariable analysis revealed that variables independently associated with shorter progression-free survival (PFS) included thrombocytopenia, and translocation and the TT genotype of the 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, translocation and the TT genotype of the gene (686C > T) were independent prognostic factors associated with shorter overall survival (OS) (median OS: 8 vs. 45 months; HR = 7.08). The evaluation of the SNP 686C > T of the gene could be used as a diagnostic tool in MM patients at risk of early disease progression and death.