Diagnosing and managing advanced chronic myeloid leukemia

Area of Science:

• Hematology
• Oncology
• Molecular Biology

Background:

• Clinical staging of chronic myeloid leukemia (CML) includes chronic phase (CP-CML), accelerated phase (AP-CML), and blastic phase (BP-CML).
• Transformation from CP-CML to AP/BP-CML involves loss of differentiation and is associated with various somatic mutations.
• Tyrosine kinase inhibitor (TKI)-resistant CP-CML shares molecular similarities with AP/BP-CML.

Purpose of the Study:

• To analyze the clinical and molecular characteristics of CML progression.
• To evaluate the predictive value of morphology versus molecular markers in CML.
• To highlight the importance of molecular monitoring in TKI therapy for CML.

Main Methods:

• Analysis of clinical staging, morphological changes, and somatic mutations in CML.
• Gene expression profiling of different CML phases and TKI resistance.
• Review of clinical outcomes and treatment strategies for advanced CML.

Main Results:

• Morphology is an unreliable predictor of CML biologic behavior; gene expression profiles of TKI-resistant CP-CML resemble AP/BP-CML.
• Progression to AP/BP-CML or TKI resistance significantly impacts survival.
• BCR-ABL1 mutations are frequent causes of TKI resistance, but alternative pathways also contribute.

Conclusions:

• Identifying patients failing TKI milestones or progressing requires molecular monitoring.
• Salvage TKI selection depends on prior treatment, comorbidities, and mutation status.
• Therapy for AP/BP-CML remains challenging, often necessitating toxic treatments like HSCT.