Andersson Emma I, Brück Oscar, Braun Till, Mannisto Susanna, Saikko Leena, Lagström Sonja, Ellonen Pekka, Leppä Sirpa, Herling Marco, Kovanen Panu E, Mustjoki Satu
Hematology Research Unit Helsinki, Department of Hematology, University of Helsinki and Helsinki University Hospital Comprehensive Cancer Center, 00290 Helsinki, Finland.
Translational Immunology Research program and Department of Clinical Chemistry and Hematology, University of Helsinki, 00014 Helsinki, Finland.
Cancers (Basel). 2020 Mar 16;12(3):702. doi: 10.3390/cancers12030702.
Peripheral T-cell lymphomas (PTCL) are a heterogeneous, and often aggressive group of non-Hodgkin lymphomas. Recent advances in the molecular and genetic characterization of PTCLs have helped to delineate differences and similarities between the various subtypes, and the JAK/STAT pathway has been found to play an important oncogenic role. Here, we aimed to characterize the JAK/STAT pathway in PTCL subtypes and investigate whether the activation of the pathway correlates with the frequency of gene mutations. Patient samples from AITL ( = 30), ALCL ( = 21) and PTCL-NOS ( = 12) cases were sequenced for , and mutations using amplicon sequencing and stained immunohistochemically for pSTAT3, pMAPK, and pAKT. We discovered mutations in 13% of AITL, 13% of ALK ALCL, 38% of ALK ALCL and 17% of PTCL-NOS cases. However, no mutations were found and mutations were only present in ALK ALCL (15%). Concurrent mutations were found in all subgroups except ALK ALCL where mutations were always seen alone. High pY-STAT3 expression was observed especially in AITL and ALCL samples. When studying JAK-STAT pathway mutations, pY-STAT3 expression was highest in PTCLs harboring either or mutations and CD30 phenotype representing primarily ALK ALCLs. Further investigation is needed to elucidate the molecular mechanisms of JAK-STAT pathway activation in PTCL.
外周T细胞淋巴瘤（PTCL）是一组异质性且通常具有侵袭性的非霍奇金淋巴瘤。PTCL分子和基因特征的最新进展有助于明确不同亚型之间的差异和相似之处，并且发现JAK/STAT通路发挥重要的致癌作用。在此，我们旨在描述PTCL各亚型中的JAK/STAT通路，并研究该通路的激活是否与基因突变频率相关。对30例血管免疫母细胞性T细胞淋巴瘤（AITL）、21例间变性大细胞淋巴瘤（ALCL）和12例非特指外周T细胞淋巴瘤（PTCL-NOS）患者的样本进行扩增子测序，检测JAK1、JAK2和STAT3基因突变情况，并进行pSTAT3、pMAPK和pAKT免疫组织化学染色。我们在13%的AITL、13%的ALK阳性ALCL、38%的ALK阴性ALCL和17%的PTCL-NOS病例中发现了JAK1基因突变。然而，未发现JAK2基因突变，STAT3基因突变仅存在于ALK阳性ALCL中（15%）。除ALK阳性ALCL中STAT3基因突变总是单独出现外，在所有亚组中均发现了并发突变。尤其在AITL和ALCL样本中观察到高磷酸化Y-STAT3表达。在研究JAK-STAT通路突变时，pY-STAT3表达在携带JAK1或STAT3基因突变且具有CD30表型（主要代表ALK阴性ALCL）的PTCL中最高。需要进一步研究以阐明PTCL中JAK-STAT通路激活的分子机制。
