In recent years, it has become clear that members of the signal transducer and activator of transcription (STAT) family of genes play an important role in cancer. The STAT family consists of seven genes, STAT1-4, STAT5A, STAT5B and STAT6, that are involved in regulating cellular proliferation, apoptosis, angiogenesis and the immune system response. Constitutive activation of STAT3, via mutational changes, is important in oncogenesis in both solid and hematopoietic cancers. In the case of hematopoietic neoplasms, STAT3 driver mutations have been described in T-cell large granular lymphocytic (T-LGL) leukemia and chronic natural killer lymphoproliferative disorders (CLPD-NK) and are seen in 30%-40% of T-LGL leukemia patients. STAT5B is also mutated in T-LGL leukemia and CLPD-NK, but in a much smaller proportion. Here we review past and current research on STAT genes in hematopoietic and solid cancers with emphasis on STAT3 and STAT5B and their roles in the pathogenesis of hematopoietic malignancies, particularly T-LGL leukemia and CLPD-NK.

Angioimmunoblastic T‑cell lymphoma (AITL) is a uniquely aggressive mature T‑cell neoplasm. In recent years, recurrent genetic mutations in ras homolog family member A (RHOA), tet methylcytosine dioxygenase 2 (TET2), DNA methyltransferase 3 alpha (DNMT3A) and isocitrate dehydrogenase [NADP(+)] 2 (IDH2) have been identified as associated with AITL. However, a deep molecular study assessing both DNA mutations and RNA expression profile combined with digital image analysis is lacking. The present study aimed to evaluate the significance of molecular and morphologic features by high resolution digital image analysis in several cases of AITL. To do so, a total of 18 separate tissues from 10 patients with AITL were collected and analyzed. The results identified recurrent mutations in RHOA, TET2, DNMT3A, and IDH2, and demonstrated increased DNA mutations in coding, promoter and CCCTC binding factor (CTCF) binding sites in RHOA mutated AITLs vs. RHOA non‑mutated cases, as well as increased overall survival in RHOA mutated patients. In addition, single cell computational digital image analysis morphologically characterized RHOA mutated AITL cells as distinct from cells from RHOA mutation negative patients. Computational analysis of single cell morphological parameters revealed that RHOA mutated cells have decreased eccentricity (more circular) compared with RHOA non‑mutated AITL cells. In conclusion, the results from the present study expand our understanding of AITL and demonstrate that there are specific cell biological and morphological manifestations of RHOA mutations in cases of AITL.

Anaplastic lymphoma kinase (ALK) positive large B-cell lymphoma (ALK+ LBCL) is an aggressive and rare subtype of B-cell lymphoma. Patients typically present with advanced clinical stage disease and do not respond to conventional chemotherapy; the median overall survival is 1.8 years. The genetic landscape of this entity remains poorly understood. Here we report a unique case of ALK+ LBCL harbouring a rare TFG::ALK fusion. Targeted next-generation sequencing showed no significant single nucleotide variants, insertions/deletions, or other structural variants beyond the TFG::ALK fusion; deep deletions of FOXO1, PRKCA, and the MYB locus were also detected. Our case report draws attention to this rare disease, highlights a need for larger genetic profiling studies, and focuses on the pathogenesis and potential therapeutic targets of this aggressive disease. To our knowledge, this is the first report of a TFG::ALK fusion in ALK+ LBCL.