Patients with chronic myeloid leukemia (CML) who show a sharp increase in ABCB1 mRNA expression within 3 weeks of starting imatinib treatment had poorer early molecular response, major molecular response, and event-free survival, according to a study published in Leukemia.1
Laura Eadie, PhD, a postdoctoral researcher in the Cancer Theme at the South Australian Health and Medical Research Institute (SAHMRI) in Adelaide, as well as the study’s lead researcher, said these results are the first evidence that monitoring ABCB1 mRNA expression within the first month of imatinib treatment could identify patients most likely to develop imatinib resistance.
“Some patients were found to have higher levels of P-glycoprotein in their leukemic cells after just a few weeks of starting therapy. These patients were much more likely to develop resistance to Glivec later on,” she said. “We’ve found that increase in P-glycoprotein in patients is correlated with risk of becoming resistant and not responding to the drug, or even of succumbing to disease.
“It didn’t matter if the patient had high levels at diagnosis. It was more the change in levels of ABCB1.
Tyrosine kinase inhibitors (TKIs) effectively target the fusion protein Bcr-Abl in patients with CML, but up to 35% of patients treated with imatinib will exhibit primary or secondary resistance.
The most common mechanism of secondary resistance is mutation in the Bcr-Abl kinase domain, but Dr Eadie and colleagues suspected that increased ABCB1 mRNA levels could identify patients likely to develop resistance to imatinib.