Psoriasis (Auckland, N.Z.) · 2025
Psoriasis: Prevalence, Clinical Variants and Quality of Life, Among Patients Attending the Skin Clinic at Mbarara Regional Referral Hospital, Uganda.
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Russler-Germain David A, Krysiak Kilannin, Ramirez Cody, Mosior Matthew, Watkins Marcus P, Gomez Felicia, Skidmore Zachary L, Trani Lee, Gao Feng, Geyer Susan, Cashen Amanda F, Mehta-Shah Neha, Kahl Brad S, Bartlett Nancy L, Alderuccio Juan P, Lossos Izidore S, Ondrejka Sarah L, Hsi Eric D, Martin Peter, Leonard John P, Griffith Malachi, Griffith Obi L, Fehniger Todd A
Аннотация
Follicular lymphoma (FL) is clinically heterogeneous, with select patients tolerating extended watch-and-wait, whereas others require prompt treatment, suffer progression of disease within 24 months of treatment (POD24), and/or experience aggressive histologic transformation (t-FL). Because our understanding of the relationship between genetic alterations in FL and patient outcomes remains limited, we conducted a clinicogenomic analysis of 370 patients with FL or t-FL (from Cancer and Leukemia Group B/Alliance trials 50402/50701/50803, or real-world cohorts from Washington University School of Medicine, Cleveland Clinic, or University of Miami). FL subsets by grade, stage, watch-and-wait, or POD24 status did not differ by mutation burden, whereas mutation burden was significantly higher in relapsed/refractory (rel/ref) FL and t-FL than in newly diagnosed (dx) FL. Nonetheless, mutation burden in dx FL was not associated with frontline progression-free survival (PFS). CREBBP was the only gene more commonly mutated in FL than in t-FL yet mutated CREBBP was associated with shorter frontline PFS in FL. Mutations in 20 genes were more common in rel/ref FL or t-FL than in dx FL, including 6 significantly mutated genes (SMGs): STAT6, TP53, IGLL5, B2M, SOCS1, and MYD88. We defined a mutations associated with progression (MAP) signature as ≥2 mutations in these 7 genes (6 rel/ref FL or t-FL SMGs plus CREBBP). Patients with dx FL possessing a MAP signature had shorter frontline PFS, revealing a 7-gene set offering insight into FL progression risk potentially more generalizable than the m7-Follicular Lymphoma International Prognostic Index (m7-FLIPI), which had modest prognostic value in our cohort. Future studies are warranted to validate the poor prognosis associated with a MAP signature in dx FL, potentially facilitating novel trials specifically in this high-risk subset of patients.