Mechanism of treatment-free remission in patients with chronic myeloid leukemia revealed by a computational model of CML evolution
Lai, X.; Jiao, X.; Zhang, H.; Lei, J.
Show abstract
In the past few years, international treatment guidelines for chronic myeloid leukemia (CML) have incorporated recommendations for attempting discontinuation of treatment with tyrosine kinase inhibitors (TKIs) outside of the setting of a clinical trial with the aim of treatment-free remission (TFR). Multiple clinical studies have shown consistent results that 40%-50% patients can achieve long-term TFR after TKI discontinuation, and most relapse patients undergo molecular recurrence within 6 months after TKI discontinuation, however the underling mechanisms remain unclear. To understand the mechanism of TFR in patients with CML, we consider the competition between leukemia stem cell and bone marrow microenvironment, and develop a mathematical model to investigate the CML progression dynamics. Model simulations are consistent with clinical observation of CML progression, and reveal a mechanism of dimorphic response after TKI discontinuation. Our model predicts that neoplasitic microenvironment is significant for CML occurrence and progression. We furthermore discuss the prediction of TFR based on the change rates of microenvironment index and leukemia stem cells ratio prior TKI discontinuation.
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- DNFE: Directed-network flow entropy for detecting the tipping points during biological processes 94%
- scPADGRN: A preconditioned ADMM approach for reconstructing dynamic gene regulatory network using single-cell RNA sequencing data 93%
- Neural Network Models for Sequence-Based TCR and HLA Association Prediction 92%
Similar papers in this journal
Similar papers in this journal
- A Logic-incorporated Gene Regulatory Network Deciphers Principles in Cell Fate Decisions 93%
- Wavenumber-dependent transmission of subthreshold waves on electrical synapses network model of Caenorhabditis elegans 92%
- Mapping of single-cell landscape of acral melanoma and analysis of molecular regulatory network of tumor microenvironment 92%
Similar papers in this journal
- Predicting Minimal Residual Disease in Acute Myeloid Leukemia through Stochastic Modeling of Clonality 94%
- A virtual B cell lymphoma model to predict effective combination therapy 91%
- Hematopoietic recovery after transplantation is primarily derived from the stochastic contribution of hematopoietic stem cells 87%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.