STAT3 mutations ID'd in rare lymphoproliferative disorder

Share this content:
<i>STAT3</i> Mutations ID'd in Rare Lymphoproliferative Disorder
STAT3 Mutations ID'd in Rare Lymphoproliferative Disorder

THURSDAY, May 17 (HealthDay News) -- Approximately 40 percent of patients with T-cell large granular lymphocytic leukemia have mutations in the Src homology 2 (SH2) dimerization and activation domain of the signal transducer and activator of the transcription 3 (STAT3) gene, according to a study published in the May 17 issue of the New England Journal of Medicine.

Hanna L.M. Koskela, M.D., of the University of Helsinki and Helsinki University Central Hospital, and colleagues used exome sequencing techniques to sequence somatic mutations in cytotoxic T lymphocytes obtained from 76 patients with T-cell large granular lymphocytic leukemia.

The researchers found that 40 percent of patients with T-cell large granular lymphocytic leukemia exhibited mutations in the STAT3 gene. Four recurrent mutational hot spots were identified, all of which were located in exon 21, encoding the SH2 domain. The resulting amino acid alterations led to a more hydrophobic protein surface and correlated with STAT3 phosphorylation and localization in the nucleus. In affected patients, there was an upregulation of downstream targets of the STAT3 pathway. Neutropenia and rheumatoid arthritis were more commonly found in patients with STAT3 mutations.

"In conclusion, STAT3 is frequently mutated in large granular lymphocytic leukemia, highlighting key steps in the molecular pathogenesis of this rare disease," the authors write. "Structural and functional data suggest that the observed mutations result in STAT3 hyperactivation and may confer ligand-independent signaling."

Several authors disclosed financial relationships with pharmaceutical and diagnostic technology companies.

Full Text (subscription or payment may be required)

You must be a registered member of ONA to post a comment.

Sign Up for Free e-newsletters

Regimen and Drug Listings


Bone Cancer Regimens Drugs
Brain Cancer Regimens Drugs
Breast Cancer Regimens Drugs
Endocrine Cancer Regimens Drugs
Gastrointestinal Cancer Regimens Drugs
Genitourinary Cancer Regimens Drugs
Gynecologic Cancer Regimens Drugs
Head and Neck Cancer Regimens Drugs
Hematologic Cancer Regimens Drugs
Lung Cancer Regimens Drugs
Other Cancers Regimens
Rare Cancers Regimens
Skin Cancer Regimens Drugs