Genomic CCR4 mutations and schema of mechanistic explanations of mogamulizumab resistance. Shown are the CCR4 gene and its domains that include mutations (pink circles) identified in 3 patients treated with mogamulizumab in relation to (A) the mogamulizumab binding epitope, (B-C) transmembrane domains, and (D) 1 patient as well as previously described patients with gain-of-function mutations (gray circles) in CTCL and adult T cell leukemia/lymphoma (ATLL). Beygi et al consider 3 mechanistic aspects of mogamulizumab resistance: (1) detectable genomic events, (2) no detectable genomic events that lead to low or loss of CCR4 protein expression, and (3) an undetermined mechanism with preserved CCR4 expression. delins, deletion-insertion; fs, frameshift. Professional illustration by Somersault 18:24.