The discovery of tyrosine kinase inhibitors (TKIs) brought a major breakthrough in the treatment of patients with chronic myeloid leukemia (CML). But the emerging resistance to TKI therapy is a major challenge in CML treatment. Malignant cells exhibit metabolic changes when compared to their normal counterparts, owing to both genetic and epigenetic alterations. Whether the altered levels of metabolic enzymes result in alteration in total enzyme activity in TKI resistant CML clones which can be assessed from the number of their metabolites produced.

Despite the availability of imatinib mesylate, a targeted therapy for treatment of Chronic myeloid leukemia, primary and secondary resistance to therapy remains a challenge. Also, patients progressing to blast crisis phase show little response to imatinib. Previous studies in the lab on generation of proteomic and genomic profile of imatinib sensitive and resistant CML cells have generated data which is being explored to understand disease progression and concommittent resistance to TKIs.

Chronic myeloid leukemia (CML) epitomises successful targeted therapy with 90% patients in chronic phase treated with tyrosine kinase inhibitors (TKIs) attaining remission. This success eludes 80% patients in advanced phase of blast crisis (BC) who are resistant to TKIs and have poor survival. Since continued administration of TKIs is necessary to sustain remission, patients are on TKIs for a longer period with higher probability of resistance, relapse and progression to BC.

Chronic myeloid leukemia (CML) epitomises successful targeted therapy with 90% patients in chronic phase treated with tyrosine kinase inhibitor (TKI) attaining remission. This success eludes 80% patients in advanced blast crisis (BC) resistant to TKIs due to either kinase domain mutations in the transforming protein Bcr/Abl preventing TKI binding or progression of leukemic cells to Bcr/Abl independent phenotype wherein alternate signalling pathways drive the disease. This brings in a need to identify alternate therapeutic targets for TKI resistant CML-BC.

The molecular mechanism mediating expression of senescent cell antigen-aggregated or cleaved band 3 and externalized phosphatidylserine (PS) on the surface of aged erythrocytes and their premature expression in certain anemias is not completely elucidated. The erythrocytes with these surface modifications undergo macrophage-mediated phagocytosis. In this study, the role of protein kinase C (PKC) isoforms in the expression of these surface modifications was investigated.