Major PTCL subtypes and association with T_H cell states/cell-of-origin and genetic alteration. Although there is evidence from molecular or GEP studies indicating the association of transcriptional programs of major T_H subset with PTCL subtypes, the genetic data suggest that specific driver genetic lesions may skew a naïve CD4⁺ T cell toward a T_H differentiation to maintain that cell state and may take part with other genetic aberrations crucial for lymphomagenesis. It is also plausible that the genetic defects acquired along with transformation can modulate differentiation profiles and forced plasticity. Each colored box depicts mutation landscape and copy number data summarized from several recent genomic studies. The frequency of recurrent mutations/CN is arranged from left to right based on the frequency reported in the literature. Currently in-use and potential therapeutic targets are listed per cell state (Mereu et al,¹⁸³ Feldman et al,¹⁸⁴ Iqbal et al,³⁸ Iqbal et al,¹⁰ Herek et al,¹⁵⁸ Yu and Zhang,¹⁸⁵ Sun et al,¹⁸⁶ Liu et al,¹⁸⁷ Bongiovanni et al,¹⁸⁸ and Thakral et al¹⁸⁹). ALKi, ALK inhibitor; BV, brentuximab vedotin; CN, copy number.