The backbone of therapy for chronic lymphocytic leukemia (CLL) is the combination of fludarabine and cyclophosphamide (FC). In order to exert its cytotoxic effect, cyclophosphamide must first be converted to its active form by CYP2B6, an isoform of cytochrome P450.
In this week's issue of Blood, Johnson and colleagues present a study discussing the impact of genetic variation in CYP2B6 on CLL response to FC regimens by screening for the most common variant of CYP2B6 that defines the *6 allele. The results demonstrate important implications for pharmacogenetic analysis influencing individualized dosing and/or choice of therapeutic agents in the future.
CYP2B6*6 is an independent determinant of inferior response to fludarabine plus cyclophosphamide in chronic lymphocytic leukemia, Gillian G. Johnson, Ke Lin, Trevor F. Cox, Melanie Oates, David R. Sibson, Richard Eccles, Bryony Lloyd, Laura-Jayne Gardiner, Daniel F. Carr, Munir Pirmohamed, Jonathan C. Strefford, David G. Oscier, David Gonzalez de Castro, Monica Else, Daniel Catovsky, and Andrew R. Pettitt, Blood - doi: 10.1182/blood-2013-07-516666