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Molecular response in newly diagnosed chronic-phase chronic myeloid leukemia: prediction modeling and pathway analysis

Authors :
Jerald P. Radich
Matthew Wall
Susan Branford
Catarina D. Campbell
Shalini Chaturvedi
Daniel J. DeAngelo
Michael Deininger
Justin Guinney
Andreas Hochhaus
Timothy P Hughes
Hagop M. Kantarjian
Richard A. Larson
Sai Li
Rodrigo Maegawa
Kaushal Mishra
Vanessa Obourn
Javier Pinilla-Ibarz
Das Purkayastha
Islam Sadek
Giuseppe Saglio
Alok Shrestha
Brian S. White
Brian J. Druker
Source :
Haematologica, Vol 108, Iss 6 (2023)
Publication Year :
2023
Publisher :
Ferrata Storti Foundation, 2023.

Abstract

Tyrosine kinase inhibitor therapy revolutionized chronic myeloid leukemia treatment and showed how targeted therapy and molecular monitoring could be used to substantially improve survival outcomes. We used chronic myeloid leukemia as a model to understand a critical question: why do some patients have an excellent response to therapy, while others have a poor response? We studied gene expression in whole blood samples from 112 patients from a large phase III randomized trial (clinicaltrials gov. Identifier: NCT00471497), dichotomizing cases into good responders (BCR::ABL1 ≤10% on the International Scale by 3 and 6 months and ≤0.1% by 12 months) and poor responders (failure to meet these criteria). Predictive models based on gene expression demonstrated the best performance (area under the curve =0.76, standard deviation =0.07). All of the top 20 pathways overexpressed in good responders involved immune regulation, a finding validated in an independent data set. This study emphasizes the importance of pretreatment adaptive immune response in treatment efficacy and suggests biological pathways that can be targeted to improve response.

Details

Language :
English
ISSN :
03906078 and 15928721
Volume :
108
Issue :
6
Database :
Directory of Open Access Journals
Journal :
Haematologica
Publication Type :
Academic Journal
Accession number :
edsdoj.0ea048e8ba4f46a6a15bd5a4b185ec55
Document Type :
article
Full Text :
https://doi.org/10.3324/haematol.2022.281878