Cytokine studies in thrombocytosis. (A) Cytokines (n = 15) were quantified from ET (n = 20), RT (n = 18), or healthy controls (n = 14), and the normalized data (centered and scaled) were used for unsupervised hierarchical clustering using aggregated data; P values corresponding to group differences were determined by using Kruskal-Wallis tests); scale bar is shown. (B) PC analysis was applied to cytokine levels for data reduction, and iteratively applied to ET, RT, or healthy cohorts; note the general segregation of ET from RT and healthy controls. (C) Box plots show normalized cytokine levels by cohort; group-wise (upper panels) and statistically different pairwise P values are shown. (D-E) PC analysis applied to cytokine levels was iteratively applied to ET cohorts delineated by JAK2^V617F (D) or IFNA16 rs28368163 genotype (E). In both panels D and E, mutant alleles are in red. (F-H) IFN-α16 was quantified by enzyme-linked immunosorbent assay from ET (n = 19 [1 of 20 samples was censored for a technical limitation]) and healthy controls (n = 20), substratified according to IFNA16 or JAK2^V617F genotype. Mutant alleles in panels G and H are in red. P values using the t test are shown. *P < .05, **P < .01, ***P < .001, ****P < .0001. CD258, tumor necrosis factor superfamily member 14; CD30, TNF receptor superfamily member 8; IFN, IFNs α, β, γ; IL, interleukins 6, 8, 10, or 1β; IL1RA, IL-1 receptor antagonist; N.S., not significant; TNFα, tumor necrosis factor α; TNFRI, TNF receptor type 1 cytokine; TNFRII, TNF receptor 2 cytokine; TSLP, thymic stromal lymphopoietin; Tweak, TNF-like weak inducer of apoptosis.