• Andres Jerez, Michael J Clemente, Hideki Makishima, Hanna Rajala, Ines Gómez-Seguí, Thomas Olson, Kathy McGraw, Bartlomiej Przychodzen, Austin Kulasekararaj, Manuel Afable, Holleh D Husseinzadeh, Naoko Hosono, Francis LeBlanc, Sonja Lagström, Dan Zhang, Pekka Ellonen, André Tichelli, Catherine Nissen, Alan E Lichtin, Aleksandra Wodnar-Filipowicz, Ghulam J Mufti, Alan F List, Satu Mustjoki, Thomas P Loughran, and Jaroslaw P Maciejewski.
• Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH;
• Blood. 2013 Oct 3; 122 (14): 2453-9.

AbstractLarge granular lymphocyte leukemia (LGL) is often associated with immune cytopenias and can cooccur in the context of aplastic anemia (AA) and myelodysplastic syndromes (MDS). We took advantage of the recent description of signal transducer and activator of transcription 3 (STAT3) mutations in LGL clonal expansions to test, using sensitive methods, for the presence of these mutations in a large cohort of 367 MDS and 140 AA cases. STAT3 clones can be found not only in known LGL concomitant cases, but in a small proportion of unsuspected ones (7% AA and 2.5% MDS). In STAT3-mutated AA patients, an interesting trend toward better responses of immunosuppressive therapy and an association with the presence of human leukocyte antigen-DR15 were found. MDSs harboring a STAT3 mutant clone showed a lower degree of bone marrow cellularity and a higher frequency of developing chromosome 7 abnormalities. STAT3-mutant LGL clones may facilitate a persistently dysregulated autoimmune activation, responsible for the primary induction of bone marrow failure in a subset of AA and MDS patients.

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