P710: CLINICAL STUDY ON THE RELATIONSHIP BETWEEN NON-ABL1 KINASE REGION MUTATION AND TKI DRUG RESISTANCE AND DISEASE PROGRESSION IN CHRONIC MYELOID LEUKEMIA

Abstract

Background: The emergence of small molecule tyrosine kinase inhibitors (The Tyrosine Kinase Inhibitors, TKI) has gradually transformed chronic myelocytic leukemia (CML) from a fatal malignant disease into a chronic disease, while ABL1 kinase Kinase Domain (KD) mutation is the main reason for poor efficacy or resistance to TKIs. In recent years, with the clinical application of Next Generation Sequencing (NGS) technology, it has been found that CML patients are often accompanied by non-ABL1 kinase region gene mutations, but whether these accompanying mutations are related to the efficacy of TKIs and disease progression in CML? still uncertain. This study retrospectively analyzed the correlation between CML with non-ABL1 KD mutation and TKI efficacy and disease progression, in order to provide basis and scientific guidance for further accurate diagnosis and treatment of CML patients. Aims: To investigate the relationship between CML associated with non ABL1 Kinase Domain (KD) mutation and TKI efficacy and disease progression. Methods: 108 blood tumor related genes in 120 patients with CML were detected by Next-generation sequencing (NGS). The non ABL1 KD mutations and their relationship with relevant clinical information and ABL1 KD mutation were analyzed. Results: Non ABL1KD mutations were detected in 58 patients (48%), and the mutation proportion of patients with additional chromosome abnormalities (63%) was significantly higher than that of patients without additional chromosome abnormalities (34%) (P=0.003). In the analysis of mutation proportion in patients with different stages of CML, the mutation proportion in blastic phase(73%), accelerated phase (67%) and chronic phase (42%) decreased gradually (P=0.031). The proportion of WT1 mutation and transcriptional regulation related mutations in patients with AP CML (WT1+: 17%, P=0.027; Transcriptional regulatory mutations 42%, P=0.001) were higher than those in CP. In the analysis of TKI treatment response, the proportion of mutations detected in the best response group (30%), warning group (52%) and drug resistance group (61%) increased gradually (P=0.018). The proportion of RUNX1 mutation in TKI treatment failure group (17%) was higher than that in warning group (2%) (P=0.029). The proportion of ABL1 KD mutation in CML patients with non ABL1 KD mutation (60%) was significantly higher than that in patients without non ABL1 KD mutation (36%) (P=0.022). Summary/Conclusion: Non ABL1 KD mutations are closely related to TKI efficacy and disease progression, while WT1 and RUNX1 mutations may be new molecular targets for accurate diagnosis of CML.