Early BCR-ABL1 Transcript Decline after 1 Month of Tyrosine Kinase Inhibitor Therapy as an Indicator for Treatment Response in Chronic Myeloid Leukemia

• Published in: PloS one 2017, Vol.12 (1), p.e0171041-e0171041
• Main Authors: El Missiry, Mohamed, Hjorth-Hansen, Henrik, Richter, Johan, Olson-Strömberg, Ulla, Stenke, Leif, Porkka, Kimmo, Kreutzman, Anna, Mustjoki, Satu
• Format: Article
• Language: English
• Subjects: Antigens, CD - metabolism; Biology and Life Sciences; Blood; Bone marrow; Cancer; Care and treatment; CD34 antigen; CD38 antigen; Chi-square test; Chronic myeloid leukemia; Enzyme inhibitors; Feasibility studies; Fusion Proteins, bcr-abl - genetics; Fusion Proteins, bcr-abl - metabolism; Gene Expression Regulation, Leukemic - drug effects; Genetic aspects; Health aspects; Hematology; Hemoglobins - metabolism; Humans; Imatinib; Inhibitors; Kinases; Leukemia; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - diagnosis; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - immunology; Medical diagnosis; Medical prognosis; Medical research; Medicin och hälsovetenskap; Medicine and Health Sciences; Myeloid leukemia; Patients; Physical Sciences; Protein Kinase Inhibitors - pharmacology; Protein Kinase Inhibitors - therapeutic use; Protein-tyrosine kinase; Research and Analysis Methods; RNA, Messenger - genetics; RNA, Messenger - metabolism; Spleen; Spleen - drug effects; Spleen - pathology; Stem cells; Therapy; Time Factors; Transcription; Transcription factors; Treatment Outcome; Tyrosine; Tyrosine kinase inhibitors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0171041

In chronic myeloid leukemia (CML), early treatment prediction is important to identify patients with inferior overall outcomes. We examined the feasibility of using reductions in BCR-ABL1 transcript levels after 1 month of tyrosine kinase inhibitor (TKI) treatment to predict therapy response. Fifty-two first-line TKI-treated CML patients were included (imatinib n = 26, dasatinib n = 21, nilotinib n = 5), and BCR-ABL1 transcript levels were measured at diagnosis (dg) and 1, 3, 6, 12, 18, 24, and 36 months. The fold change of the BCR-ABL1 transcripts at 1 month compared to initial BCR-ABL1 transcript levels was used to indicate early therapy response. In our cohort, 21% of patients had no decrease in BCR-ABL1 transcript levels after 1 month and were classified as poor responders. Surprisingly, these patients had lower BCR-ABL1 transcript levels at dg compared to responders (31% vs. 48%, p = 0.0083). Poor responders also significantly more often had enlarged spleen (55% vs. 15%; p