Computational modeling reveals key factors driving treatment-free remission in chronic myeloid leukemia patients

Abstract

Patients with chronic myeloid leukemia (CML) who receive tyrosine kinase inhibitors (TKIs) have been known to achieve treatment-free remission (TFR) upon discontinuing treatment. However, the underlying mechanisms of this phenomenon remain incompletely understood. This study aims to elucidate the mechanism of TFR in CML patients, focusing on the feedback interaction between leukemia stem cells and the bone marrow microenvironment. We have developed a mathematical model to explore the interplay between leukemia stem cells and the bone marrow microenvironment, allowing for the simulation of CML progression dynamics. Our proposed model reveals a dichotomous response following TKI discontinuation, with two distinct patient groups emerging: one prone to early molecular relapse and the other capable of achieving long-term TFR after treatment cessation. This finding aligns with clinical observations and underscores the essential role of feedback interaction between leukemic cells and the tumor microenvironment in sustaining TFR. Notably, we have shown that the ratio of leukemia cells in peripheral blood (PBLC) and the tumor microenvironment (TME) index can be a valuable predictive tool for identifying patients likely to achieve TFR after discontinuing treatment. This study provides fresh insights into the mechanism of TFR in CML patients and underscores the significance of microenvironmental control in achieving TFR.