1. PTCH1 is a reliable marker for predicting imatinib response in chronic myeloid leukemia patients in chronic phase
- Author
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Eduardo Anguita, Pilar Llamas, Valentín García-Gutiérrez, Santiago Osorio, Ignacio Mahillo-Fernández, Luis Felipe Casado, Carmen Burgaleta, Juan M. Alonso-Domínguez, Ismael Buño, Pedro Sánchez-Godoy, Juan Luis Steegmann, Alicia Arenas, Joaquin Martinez-Lopez, Rafael Del Orbe, María Teresa Gómez-Casares, Rocio N. Salgado, Francisca Ferrer-Marín, and Rosa Ayala
- Subjects
0301 basic medicine ,Oncology ,Male ,Myeloid ,Cancer Treatment ,Gene Expression ,lcsh:Medicine ,Biomarkers, Pharmacological ,0302 clinical medicine ,Cell Signaling ,hemic and lymphatic diseases ,Medicine and Health Sciences ,Medicine ,lcsh:Science ,Regulation of gene expression ,Aged, 80 and over ,Multidisciplinary ,Gene Expression Regulation, Leukemic ,Myeloid leukemia ,Middle Aged ,Prognosis ,Patched-1 Receptor ,Leukemia ,medicine.anatomical_structure ,Treatment Outcome ,030220 oncology & carcinogenesis ,Leukemia, Myeloid, Chronic-Phase ,Imatinib Mesylate ,Female ,medicine.drug ,Research Article ,Signal Transduction ,Adult ,medicine.medical_specialty ,endocrine system ,Death Rates ,Antineoplastic Agents ,03 medical and health sciences ,Cytogenetics ,Young Adult ,Extraction techniques ,Internal medicine ,Genetics ,Biomarkers, Tumor ,Humans ,Demography ,Aged ,Retrospective Studies ,Treatment Guidelines ,Health Care Policy ,Receiver operating characteristic ,business.industry ,lcsh:R ,Biology and Life Sciences ,Imatinib ,Retrospective cohort study ,Cell Biology ,Reverse Transcription ,medicine.disease ,RNA extraction ,Research and analysis methods ,Health Care ,030104 developmental biology ,PTCH1 ,People and Places ,Hedgehog Signaling ,lcsh:Q ,business - Abstract
Patched homolog 1 gene (PTCH1) expression and the ratio of PTCH1 to Smoothened (SMO) expression have been proposed as prognostic markers of the response of chronic myeloid leukemia (CML) patients to imatinib. We compared these measurements in a realistic cohort of 101 patients with CML in chronic phase (CP) using a simplified qPCR method, and confirmed the prognostic power of each in a competing risk analysis. Gene expression levels were measured in peripheral blood samples at diagnosis. The PTCH1/SMO ratio did not improve PTCH1 prognostic power (area under the receiver operating characteristic curve 0.71 vs. 0.72). In order to reduce the number of genes to be analyzed, PTCH1 was the selected measurement. High and low PTCH1 expression groups had significantly different cumulative incidences of imatinib failure (IF), which was defined as discontinuation of imatinib due to lack of efficacy (5% vs. 25% at 4 years, P = 0.013), probabilities of achieving a major molecular response (81% vs. 53% at first year, P = 0.02), and proportions of early molecular failure (14% vs. 43%, P = 0.015). Every progression to an advanced phase (n = 3) and CML-related death (n = 2) occurred in the low PTCH1 group (P
- Published
- 2017