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It remains challenging in chronic lymphocytic leukemia (CLL) to distinguish between patients with favorable and unfavorable time to first treatment (TTFT). Additionally, the downstream protein correlates of well-known molecular features of CLL are not always clear. To address this, we selected 40 CLL patients with TTFT ≤ 24 months and compared their B cell intracellular protein expression with 40 age- and sex-matched CLL patients with TTFT > 24 months using mass spectrometry. In total, 3268 proteins were quantified in the cohort. IGHV mutational status and trisomy 12 were most impactful on the CLL proteome. Comparing cases to controls, five proteins were significantly upregulated, whereas three proteins where significantly downregulated. Of these, only THEMIS2, a signaling protein acting downstream of the B cell receptor, was significantly associated with TTFT, independently of IGHV and TP53 mutational status (HR 2.49, [95%CI 1.62–3.84], P |
