Natural Products Targeting BCR-ABL: A Plant-Based Approach to Chronic Myeloid Leukemia Treatment

The BCR-ABL fusion oncoprotein, a constitutively active tyrosine kinase, plays a central role in the pathogenesis of chronic myeloid leukemia (CML). While tyrosine kinase inhibitors (TKIs) have transformed CML treatment, issues such as drug resistance, particularly involving mutations like T315I, and adverse effects underscore the need for alternative or complementary therapeutic strategies. Natural products derived from plants have long served as a reservoir for anticancer agents, offering structural diversity and multi-targeted bioactivity. Notably, many plant-based compounds exhibit anticancer effects with comparatively lower toxicity and fewer side effects than synthetic TKIs, making them attractive candidates for safer long-term use. This review explores the recent advances in plant-based natural compounds that directly or indirectly inhibit BCR-ABL kinase activity and its downstream signaling pathways. Key compounds are discussed with respect to their mechanisms of action, structure-activity relationships, and potential to overcome TKI resistance. Several of these compounds directly target BCR-ABL or promote its degradation, while others inhibit downstream effectors such as STAT5 and PI3K/Akt, leading to apoptosis and growth inhibition of leukemic cells. The synergistic potential of these natural products with existing TKIs and their promise to target drug-resistant CML cells further highlight their translational value. By integrating insights from molecular pharmacology, medicinal chemistry, and leukemia biology, this review supports the continued investigation of plant-derived agents as novel or adjunctive therapies against BCR-ABL-driven leukemias.