STAT3 mutations indicate the presence of subclinical T-cell clones in a subset of aplastic anemia and myelodysplastic syndrome patients
| Autor: | Austin G. Kulasekararaj, Satu Mustjoki, Bartlomiej P Przychodzen, Hanna Rajala, Catherine Nissen, Sonja Lagström, Inés Gómez-Seguí, Dan Zhang, Thomas P. Loughran, Holleh D Husseinzadeh, Andres Jerez, Thomas L. Olson, Aleksandra Wodnar-Filipowicz, Manuel G. Afable, Alan F. List, Michael J. Clemente, Pekka Ellonen, Ghulam J. Mufti, Naoko Hosono, Francis R LeBlanc, Alan E. Lichtin, Hideki Makishima, Kathy L. McGraw, Jaroslaw P. Maciejewski, André Tichelli |
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| Rok vydání: | 2013 |
| Předmět: |
Adult
Male STAT3 Transcription Factor medicine.medical_treatment Immunology Chronic myelomonocytic leukemia Context (language use) Cell Separation Kaplan-Meier Estimate Biology Biochemistry 03 medical and health sciences 0302 clinical medicine hemic and lymphatic diseases medicine Humans Aplastic anemia Proportional Hazards Models 030304 developmental biology Chromosome 7 (human) 0303 health sciences Reverse Transcriptase Polymerase Chain Reaction Myelodysplastic syndromes Bone marrow failure Anemia Aplastic Myeloid leukemia Immunosuppression Cell Biology Hematology Middle Aged Flow Cytometry medicine.disease 3. Good health Leukemia Large Granular Lymphocytic Myelodysplastic Syndromes 030220 oncology & carcinogenesis Mutation Cancer research Female |
| Zdroj: | Blood. 122:2453-2459 |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | Large 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. |
| Databáze: | OpenAIRE |
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