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PURPOSE: STAT3 is a key transcription factor that mediates cancer progression through phosphorylation or gain-of-function mutations. STAT3 activation in myeloid neoplasms (MNs) is primarily mediated through phosphorylation. STAT3 mutation has only rarely been reported in MNs. EXPERIMENTAL DESIGN: We assessed the clinicopathologic and molecular genetic features of 32 STAT3-mutated MNs. RESULTS: The frequency of STAT3 mutation in MNs was <0.5%. Twenty (62.5%) cases were classified as acute myeloid leukemia (AML), 7 (21.9%) as myelodysplastic syndrome (MDS), 5 (15.6%) as chronic myelomonocytic leukemia (CMML), but none as myeloproliferative neoplasms (MPN). STAT3 mutations occurred at initial diagnosis in 22 (88%) cases, or at relapse or upon leukemic transformation. Clonal hierarchy analysis revealed that STAT3 mutations represented the dominant clone in 30% of AML cases, but were subclonal in MDS and CMML. Most were missense mutations located at the SH2 domain, Y640F being the most common. STAT3 mutation was accompanied by co-existing mutations in all cases, most frequently SRSF2, TET2, ASXL1, and SETBP1. STAT3 mutations were usually associated with morphologic dysplasia, increased blasts, and monosomy 7/del7q. With a median follow-up of 24.5 months, 21 patients died, 6 had persistent disease, and 5 achieved complete remission after stem cell transplantation. CONCLUSIONS: STAT3 mutation is present in various MNs, but not in MPN. It is often an early event or occurs upon leukemic transformation, suggesting an important role in the pathogenesis and progression of MNs by activating JAK-STAT pathway. It may help identify a subset of patients with MNs who may benefit from targeted therapy.
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The simultaneous detection of BCR::ABL1 and JAK2 V617F was rarely reported and their clonal relationship and dynamic clonal shift were not characterized. Here, we described a unique case with the initial presentation as JAK2 V617F+ primary myelofibrosis, followed by the emergence of BCR::ABL1+ chronic myeloid leukemia. The patient then developed BCR::ABL1+ B-lymphoblastic leukemia. Treatment for B-lymphoblastic leukemia prompted a regression to the state of primary myelofibrosis. In light of these observations, we proposed a clonal evolution model for this case.
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Circular RNAs (circRNAs) are a class of single-stranded RNAs with covalently closed structures. Owing to their not having 3' or 5' ends, circRNAs are highly durable and insusceptible to exonuclease-mediated degradation. Moreover, some circRNAs with certain structures are translatable, making them novel vaccines. Vaccines are efficient tools for immunotherapy, such as for the prevention of infectious diseases and cancer treatment. The immune system is activated during immunotherapy to fight against abnormal allies or invaders. CircRNA vaccines represent a potential new avenue in the vaccine era. Recently, several circRNA vaccines have been synthesized and tested in vitro and in vivo. Our review briefly introduces the current understanding of the biology and function of translatable circRNAs, molecular biology, synthetic methods, delivery of circRNA, and current circRNA vaccines. We also discussed the challenges and future directions in the field by summarizing the developments in circRNA vaccines in the past few years.
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Background: Prostate cancer (PCa) ranks as the second most prevalent malignancy among males on a global scale. Accumulating evidence suggests that inflammation has an intricate relationship with tumorigenesis, tumor progression and tumor immune microenvironment. However, the overall impact of inflammation-related genes on the clinical prognosis and tumor immunity in PCa remains unclear. Methods: Machine learning methods were utilized to construct and validate a signature using The Cancer Genome Atlas (TCGA) for training, while the Memorial Sloan Kettering Cancer Center (MSKCC) and GSE70769 cohorts for independent validation. The efficacy of the signature in predicting outcomes and its clinical utility were assessed through a series of investigations encompassing in vitro experiments, survival analysis, and nomogram development. The association between the signature and precision medicine was explored via tumor immunity, genomic heterogeneity, therapeutic response, and molecular docking analyses, using bulk and single-cell RNA-sequencing data. Results: We identified 7 inflammation-related genes with prognostic significance and developed an inflammation-related prognostic signature (IRPS) with 6 genes. Furthermore, we demonstrated that both the IRPS and a nomogram integrating risk score and pathologic T stage exhibited excellent predictive ability for the survival outcomes in PCa patients. Moreover, the IRPS was found to be significantly associated with the tumor immune, genomic heterogeneity, therapeutic response, and drug selection. Conclusion: IRPS can serve as a reliable predictor for PCa patients. The signature may provide clinicians with valuable information on the efficacy of therapy and help personalize treatment for PCa patients.
