Emergence of a STAT3 mutated NK clone in LGL leukemia

Publication date: Available online 16 December 2014 Source:Leukemia Research Reports Author(s): Yiyi Yan , Thomas L. Olson , Susan B. Nyland , David J. Feith , Thomas P. Loughran Jr. Large granular lymphocyte (LGL) leukemia is a chronic clonal lymphoproliferative disorder. A patient with T-LGL leukemia was followed for 12 years; later, he developed NK-LGL leukemia with residual leukemic T-LGL. Dynamic TCRVβ usage and CDR3 sequence drifts correlating with disease progression were observed. A STAT3 S614R mutation was identified in NK cells in the NK/T-LGL mixed leukemic stage but not at earlier points. STAT3 activation in mutant samples was observed. Multiple, non-dominant T-cell clones with distinct STAT3 mutations were present throughout. Our results suggest that T and NK-LGL leukemia may share common pathogenesis mechanisms and that STAT3 mutation alone is insufficient to bring about large clonal expansions. Long-term mutational and immunological monitoring may provide diagnostic and therapeutic significance in LGL leukemia.
Source: Leukemia Research Reports - Category: Hematology Source Type: research