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

NPJ Syst Biol Appl. 2022 Oct 13;8(1):39. doi: 10.1038/s41540-022-00248-3.

Abstract

Chronic 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Fusion Proteins, bcr-abl / genetics
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / drug therapy
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / genetics
  • Protein Kinase Inhibitors* / pharmacology
  • Protein Kinase Inhibitors* / therapeutic use
  • Pyrimidines / pharmacology
  • Pyrimidines / therapeutic use

Substances

  • Protein Kinase Inhibitors
  • Pyrimidines
  • Fusion Proteins, bcr-abl
  • nilotinib