Spliceosome mutations are associated with clinical response in a phase 1b/2 study of the PLK1 inhibitor onvansertib in combination with decitabine in relapsed or refractory acute myeloid leukemia.

"rnaseq data is available under the following geo accession number: gse239678.; data availability the data generated during the current study were deposited into the gene expression omnibus (geo) database under accession number gse239678 and are available at the following url: https://www ncbi nlm nih gov/geo/query/acc cgi? data availability the data generated during the current study were deposited into the gene expression omnibus (geo) database under accession number gse239678"

"Declarations Ethics approvalThe patient protocol was approved by the institutional review board or independent ethics committees at each participating center and was in accordance with the 1964 Declaration of Helsinki and its later amendments, and with Good Clinical Practice Guidelines. Consent to participateWritten prior informed consent was provided by all patients. Conflict of interestAMZ is a Leukemia and Lymphoma Society Scholar in Clinical Research. AMZ received research funding (institutional) from Celgene/BMS, Abbvie, Astex, Pfizer, Kura, Medimmune/AstraZeneca, Boehringer-Ingelheim, Incyte, Takeda, Novartis, Shattuck Labs, Geron, Foran, and Aprea. AMZ participated in advisory boards, and/or had a consultancy with and received honoraria from AbbVie, Pfizer, Celgene/BMS, Jazz, Incyte, Agios, Servier, Boehringer-Ingelheim, Novartis, Astellas, Daiichi Sankyo, Geron, Taiho, Seattle Genetics, Otsuka, BeyondSpring, Takeda, Ionis, Amgen, Janssen, Genentech, Epizyme, Syndax, Gilead, Kura, Chiesi, ALX Oncology, BioCryst, Notable, Orum, Mendus, Zentalis, Schrodinger, Regeneron, Syros, and Tyme. AMZ served on clinical trial committees for Novartis, Abbvie, Gilead, Syros, BioCryst, Abbvie, ALX Oncology, Kura, Geron, and Celgene/BMS. PJPC and MR report personal fees from Cardiff Oncology (employment) during the conduct of the study and outside the submitted work, as well as a pending patent for US 2023/0183814. SLS reports personal fees from Cardiff Oncology (consultancy). TLL reports support from Bio-path Holdings, Astella Pharma, Celyad, Aptevo Therapeutics, Cleave Biosciences, and Ciclomed. PSB reports support from Accordant Health Services/CVS Caremark (Medical Advisory Board), Glycomimetics, Notable Labs, and GPCR. ESW participated in advisory boards, and/or had a consultancy with and received honoraria from Abbvie, Astellas Pharma, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Jazz Pharmaceuticals, Kite/Gilead, Novartis, Pfizer, Pharmaessentia, and Takeda. ESW has participated in a Speaker’s Bureau with Astellas Pharma, Dava Oncology, Pfizer, and Kura Oncology. Conflict of interest AMZ is a Leukemia and Lymphoma Society Scholar in Clinical Research. AMZ received research funding (institutional) from Celgene/BMS, Abbvie, Astex, Pfizer, Kura, Medimmune/AstraZeneca, Boehringer-Ingelheim, Incyte, Takeda, Novartis, Shattuck Labs, Geron, Foran, and Aprea. AMZ participated in advisory boards, and/or had a consultancy with and received honoraria from AbbVie, Pfizer, Celgene/BMS, Jazz, Incyte, Agios, Servier, Boehringer-Ingelheim, Novartis, Astellas, Daiichi Sankyo, Geron, Taiho, Seattle Genetics, Otsuka, BeyondSpring, Takeda, Ionis, Amgen, Janssen, Genentech, Epizyme, Syndax, Gilead, Kura, Chiesi, ALX Oncology, BioCryst, Notable, Orum, Mendus, Zentalis, Schrodinger, Regeneron, Syros, and Tyme. AMZ served on clinical trial committees for Novartis, Abbvie, Gilead, Syros, BioCryst, Abbvie, ALX Oncology, Kura, Geron, and Celgene/BMS. PJPC and MR report personal fees from Cardiff Oncology (employment) during the conduct of the study and outside the submitted work, as well as a pending patent for US 2023/0183814. SLS reports personal fees from Cardiff Oncology (consultancy). TLL reports support from Bio-path Holdings, Astella Pharma, Celyad, Aptevo Therapeutics, Cleave Biosciences, and Ciclomed. PSB reports support from Accordant Health Services/CVS Caremark (Medical Advisory Board), Glycomimetics, Notable Labs, and GPCR. ESW participated in advisory boards, and/or had a consultancy with and received honoraria from Abbvie, Astellas Pharma, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Jazz Pharmaceuticals, Kite/Gilead, Novartis, Pfizer, Pharmaessentia, and Takeda. ESW has participated in a Speaker’s Bureau with Astellas Pharma, Dava Oncology, Pfizer, and Kura Oncology."

"Funding This work was sponsored and funded entirely by Cardiff Oncology Inc."