Acute myeloid leukemia

KIT pathway upregulation predicts dasatinib efficacy in acute myeloid leukemia

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Fig. 1: Dasatinib has high sensitivity in AML patient samples compared to AML cell lines.
Fig. 2: KIT pathway enrichment is associated with dasatinib efficacy.

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Acknowledgements

We are grateful to the patients who donated samples to the study and thank the FIMM High Throughput Biomedicine Unit and Breeze DSRT data analysis pipeline teams for their support. The research was funded by the Finnish Cultural Foundation (DM), the Blood Disease Foundation Finland (DM), Finnish Hematology Association SHY (DM and AK), Ida Montinin Foundation (DM), EMBO short-term fellowship (AK), the Academy of Finland (Center of Excellence for Translational Cancer Biology; Grants 310507, 313267, 326238 to TA; 277293 to KW; iCAN Digital Precision Cancer Medicine Flagship Grant 1320185 to TA and CAH), Cancer Society of Finland (DM, AK, OK, TA, KW, and CAH), Sigrid Jusélius Foundation (to OK, KP, TA, and KW), EU Systems Microscopy (FP7), TEKES/Business Finland (to OK and KP), and Novo Nordisk Foundation (to KW; NNF17CC0027852). OK supported by the Knut and Alice Wallenberg Foundation, Swedish Foundation for Strategic Research, VR environment grant. MK supported by the University of Helsinki and Finnish Medical Foundation.

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Contributions

DM, AM, and OK designed the study. DM and AM performed drug testing experiments. DM, BY, and AK analyzed and visualized the data. DM generated hypotheses and interpreted results. DM and KKJ designed and performed flow cytometry experiments. MK performed cell line variant calling, and SP performed drug response data quality analysis. DM wrote the manuscript. MKo and KP obtained ethical permits, collected clinical samples and administered therapies. KP, MKo, TA, MW, KW, CAH, AM, and OK provided critical review. All authors contributed to and approved the final version of the manuscript.

Corresponding author

Correspondence to Disha Malani.

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Conflict of interest

The senior authors have received collaborative research grants for other projects as listed: OK received research funding from Vinnova for collaboration between Astra-Zeneca, Takeda, Pelago, and Labcyte. OK is also a board member and a co-founder of Medisapiens and Sartar Therapeutics, and has received a royalty on patents licensed by Vysis-Abbot. KP received honoraria and research funding from Bristol-Myers Squibb, Celgene, Novartis, and Pfizer. CH received honoraria from Celgene, Novartis, and Roche, and research funding from Celgene, Novartis, Oncopeptides, Pfizer, and the IMI2 project HARMONY. KW received research funding from Novartis and Pfizer. MKo: research funding from AbbVie. The remaining authors declare that they have no conflict of interest.

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Malani, D., Yadav, B., Kumar, A. et al. KIT pathway upregulation predicts dasatinib efficacy in acute myeloid leukemia. Leukemia (2020). https://doi.org/10.1038/s41375-020-0978-7

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