STAT3 mutation analysis is performed by next-generation sequencing of all coding exons of the STAT3 gene.
The STAT3 gene encodes a signaling protein regulating transcription of a wide range of genes, including those signaling the maturation of T cells and B cells. Constitutive STAT3 activation, as a result of upregulation or mutation, is seen in a variety of solid and hematopoietic cancers. STAT3 mutations, most often Y640F, D661V/Y/H/I, and N647I, have been described in 30-40% of T-cell large granular lymphocytic (T-LGL) leukemia, 30% of chronic natural killer lymphoproliferative disorders (CLPD-NK), and more rarely in aplastic anemia, MDS, and DLBCL. Identifying STAT3 mutations can help to differentiate LGL from reactive processes. T-LGL patients with STAT3 mutations tend to present with neutropenia and have a better prognosis than T-LGL patients without this mutation. The JAK3 inhibitor, tofacitinib, has been shown to improve neutropenia in T-LGL patients, while T-LGL patients with a STAT3 Y640F mutation have been shown to be sensitive to methotrexate treatment.
- Peripheral blood: 5 mL in EDTA tube.
- Bone marrow: 2 mL in EDTA tube.
- FFPE tissue: Paraffin block is preferred. Alternatively, send 1 H&E slide plus 5-10 unstained slides cut at 5 or more microns. Please use positively-charged slides and 10% NBF fixative. Do not use zinc fixatives.
Use cold pack for transport, making sure cold pack is not in direct contact with specimen.
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