Early dynamics of chronic myeloid leukemia on nilotinib predicts deep molecular response

Author:

Okamoto Yuji,Hirano Mitsuhito,Morino Kai,Kajita Masashi K.ORCID,Nakaoka ShinjiORCID,Tsuda Mayuko,Sugimoto Kei-ji,Tamaki Shigehisa,Hisatake Junichi,Yokoyama HisayukiORCID,Igarashi Tadahiko,Shinagawa Atsushi,Sugawara Takeaki,Hara Satoru,Fujikawa Kazuhisa,Shimizu Seiichi,Yujiri ToshiakiORCID,Wakita Hisashi,Nishiwaki Kaichi,Tojo Arinobu,Aihara Kazuyuki

Abstract

AbstractChronic myeloid leukemia (CML) is a myeloproliferative disorder caused by the BCR-ABL1 tyrosine kinase. Although ABL1-specific tyrosine kinase inhibitors (TKIs) including nilotinib have dramatically improved the prognosis of patients with CML, the TKI efficacy depends on the individual patient. In this work, we found that the patients with different nilotinib responses can be classified by using the estimated parameters of our simple dynamical model with two common laboratory findings. Furthermore, our proposed method identified patients who failed to achieve a treatment goal with high fidelity according to the data collected only at three initial time points during nilotinib therapy. Since our model relies on the general properties of TKI response, our framework would be applicable to CML patients who receive frontline nilotinib or other TKIs.

Funder

MEXT | Japan Society for the Promotion of Science

MEXT | JST | Precursory Research for Embryonic Science and Technology

MEXT | Japan Science and Technology Agency

Japan Agency for Medical Research and Development

Institute of AI and Beyond of The University of Tokyo

Publisher

Springer Science and Business Media LLC

Subject

Applied Mathematics,Computer Science Applications,Drug Discovery,General Biochemistry, Genetics and Molecular Biology,Modeling and Simulation

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