A novel CIP2A and BCL-XL clinical diagnostic toolkit to predict disease progression and treatment-free remission in chronic myeloid leukaemia.

Biomarkers that predict disease progression and treatment-free remission (TFR) would be of significant clinical value in chronic myeloid leukaemia (CML). We have previously shown that CIP2A levels at diagnosis can identify patients at increased risk of progression. One mechanism by which CIP2A acts is through upregulation of the anti-apoptotic gene BCL-XL. In this study, we evaluated BCL-XL mRNA expression as a diagnostic biomarker using samples from the SPIRIT 2 and DESTINY clinical trials. In SPIRIT 2, which compared imatinib and dasatinib as first-line therapies, high BCL-XL expression was associated with treatment failure, poor early molecular response, and lower rates of MR2 and MR3 achievement in patients treated with imatinib. In the DESTINY trial, which assessed treatment de-escalation and discontinuation, BCL-XL expression was significantly higher in patients who experienced molecular relapse compared to those achieving sustained TFR. Notably, increases in BCL-XL were detectable 6 to 8 months prior to molecular relapse, suggesting it may serve as an early biomarker of unsuccessful TFR. We now propose a clinical diagnostic toolkit combining CIP2A and BCL-XL biomarkers to stratify CML patients by risk of disease progression and likelihood of achieving successful TFR.