Data from Discovery of a Novel CIP2A Variant (NOCIVA) with Clinical Relevance in Predicting TKI Resistance in Myeloid Leukemias

• DOI: 10.1158/1078-0432.c.6530211.v1
• Publication Date: 2023-04-01T06:17:17Z
• Authors: Eleonora Mäkelä; Karolina Pavic; Taru Varila; Urpu Salmenniemi; Eliisa Löyttyniemi; Srikar G. Nagelli; Tea Ammunét; Veli-Matti Kähäri; Richard E. Clark; Laura L. Elo; Venkata Kumari Ba...; Claire M. Lucas; Maija Itälä-Remes; Jukka Westermarck

<div>AbstractPurpose:<p>Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein that inhibits the tumor suppressor PP2A-B56α. However, <i>CIP2A</i> mRNA variants remain uncharacterized. Here, we report discovery a splicing variant, novel CIP2A variant (<i>NOCIVA</i>).</p>Experimental Design:<p>Characterization was performed by both 3′ and 5′ rapid amplification cDNA ends from cancer cells. The function NOCIVA assessed structural molecular biology approaches. Its clinical relevance studied in acute myeloid leukemia (AML) patient cohort two independent chronic (CML) cohorts.</p>Results:<p><i>NOCIVA</i> contains exons 1 to 13 fused 349 nucleotides intron 13. Intriguingly, first 39 <i>NOCIVA</i>-specific sequence are coding frame with exon code for 13-amino acid peptide tail nonhomologous any known human sequence. Therefore, translates unique protein. retains capacity bind B56α, but, whereas predominantly cytoplasmic protein, translocates nucleus. Indicative prevalent alternative <i>NOCIVA</i> malignancies, AML CML samples overexpress <i>NOCIVA</i>, but not mRNA. In AML, high <i>NOCIVA/CIP2A</i> expression ratio marker adverse overall survival. CML, associated inferior event-free survival among imatinib-treated patients, patients treated dasatinib or nilotinib.</p>Conclusions:<p>We discovered its predicting tyrosine kinase therapy resistance leukemias.</p></div>