Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

The Antineoplastic Role of STAT5 Inhibition in BCRABL1-Positive Cells Exposed to Pimozide Alone and in Combination with Dasatinib and Ponatinib

Version 1 : Received: 8 October 2021 / Approved: 11 October 2021 / Online: 11 October 2021 (16:17:32 CEST)

How to cite: Santoro, M.; Mancuso, S.; Tolomeo, M.; Pipitone, R.M.; Grimaudo, S.; Siragusa, S. The Antineoplastic Role of STAT5 Inhibition in BCRABL1-Positive Cells Exposed to Pimozide Alone and in Combination with Dasatinib and Ponatinib. Preprints 2021, 2021100171 (doi: 10.20944/preprints202110.0171.v1). Santoro, M.; Mancuso, S.; Tolomeo, M.; Pipitone, R.M.; Grimaudo, S.; Siragusa, S. The Antineoplastic Role of STAT5 Inhibition in BCRABL1-Positive Cells Exposed to Pimozide Alone and in Combination with Dasatinib and Ponatinib. Preprints 2021, 2021100171 (doi: 10.20944/preprints202110.0171.v1).

Abstract

Background: Though tyrosine kinase inhibitors managed to reach outstanding responses in the treatment of Chronic Myeloid Leukemia, resistance is still a challenging point, occurring in approximately 10–20% of the cases, due to several mechanisms. STAT5 expression has been strictly linked to resistance and disease progression and may thus represent a significant target to overcome resistance to TKI in CML. The aim of the study is to explore the in vitro antineoplastic role of the STAT5 inhibitor Pimozide in association with 2nd and 3rd generation inhibitors on chronic myeloid leukemia cells. Methods: The cytotoxic effect was evaluated by the Trypan blue dye exclusion test. K562 cell lines were exposed to pimozide alone and in association with ponatinib and dasatinib at different concentrations to explore the drugs association effect and the in vitro cytotoxic concentrations. Conclusions: Pimozide showed a synergic effect when associated with ponatinib and dasatinib in survival inhibition of K562 cell lines. This results are of note and pave the way for a possible in vivo associations.

Keywords

chronic myeloid leukemia; dasatinib; ponatinib; pimozide; STAT inhibitors; K562

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