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Nilotinib is a tyrosine kinase inhibitor approved by the Ministry of Food and Drug Safety for frontline and 2nd line treatment of Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML). This study aimed to confirm the safety and efficacy of nilotinib in routine clinical practice within South Korea.An open-label, multicenter, single-arm, 12-week observational post-marketing surveillance (PMS) study was conducted on 669 Korean adult patients with Ph+ CML from December 24, 2010, to December 23, 2016. The patients received nilotinib treatment in routine clinical practice settings. Safety was evaluated by all types of adverse events (AEs) during the study period, and efficacy was evaluated by the complete hematological response (CHR) and cytogenetic response.During the study period, AEs occurred in 61.3% (410 patients, 973 events), adverse drug reactions (ADRs) in 40.5% (271/669 patients, 559 events), serious AEs in 4.5% (30 patients, 37 events), and serious ADRs in 0.7% (5 patients, 8 events). Furthermore, unexpected AEs occurred at a rate of 6.9% (46 patients, 55 events) and unexpected ADRs at 1.2% (8 patients, 8 events). As for the efficacy results, CHR was achieved in 89.5% (442/494 patients), and minor cytogenetic response or major cytogenetic response was achieved in 85.8% (139/162 patients).This PMS study shows consistent results in terms of safety and efficacy compared with previous studies. Nilotinib was well tolerated and efficacious in adult Korean patients with Ph+ CML in routine clinical practice settings.

Background JAK2 mutation status is a well-known risk factor for thrombosis in patients with myeloproliferative neoplasms. However, the clinical usefulness of JAK2 allele burden is under investigation. Methods We retrospectively evaluated the impact of the JAK2 V617F allele burden on clinical characteristics and outcomes of JAK2 V617F-positive polycythemia vera (PV) and essential thrombocythemia (ET). The JAK2 V617F allele burden was measured using sequencing. Results Altogether, 127 patients with JAK2 V617F mutation (PV, N=61; ET, N=66) were included in this study. JAK2 V617F allele burdens were positively correlated with white blood cell counts, hemoglobin values, lactate dehydrogenase levels, and platelet counts. The median values of JAK2 V617F allele burden in patients with PV and ET were 58% and 30%, respectively. A JAK2 V617F allele burden of ≥30%, older age, and a higher hemoglobin level were risk factors for thrombotic events in ET. In patients with PV, older age was the only thrombotic risk factor. The 8-year probabilities of overall survival (OS) were 82.9% in all patients. A high JAK2 V617F allele burden (≥58%) was associated with poor OS in patients with PV. For the patients with ET, the difference in 8- year OS based on the JAK2 V617F allele burden was not significant. Conclusion The JAK2 V617F allele burden was correlated with hematologic parameters and clinical outcomes. Assessing the JAK2 V617F allele burden can be helpful in predicting the thrombotic risk and disease course in patients with JAK2 V617F-positive PV and ET.

Background: In 2020, colorectal cancer (CRC) had the second highest mortality rate worldwide and was the third most common cancer type among various carcinomas, accounting for 10.0% and 9.4% of all carcinomas, respectively. Although the expression of ribosomal protein L27 (RPL27) is upregulated during CRC development, oncogenic roles of RPL27 have not yet been elucidated. We aimed in this study to investigate the effect of RPL27 targeting on CRC growth and whether RPL27 gained an extra-ribosomal function during CRC development. Methods: Human CRC cell lines, HCT116 and HT29, were transfected with RPL27-specific siRNA and tested for growth inhibition and apoptotic induction using MTS, FACS and Western blotting. To obtain insights into the molecular changes in response to RPL27 knockdown, global changes in gene expression were examined using RNA sequencing. Results: We observed that inhibition of RPL27 expression suppresses CRC cell growth and long-term colony formation through an induction of apoptotic cell death. Targeting RPL27 also significantly inhibited the growth of human CRC xenografts in nude mice. Noticeably, polo-like kinase 1 (PLK1), which is known to play an important role in mitotic cell cycle progression and stemness, was commonly down-regulated in both HCT116 and HT29 cells with RPL27 depletion. Western blot analysis confirmed that RPL27 silencing reduces the levels of PLK1 protein and G2/M-associated regulators, such as p-CDC25C, CDK1, and cyclin B1. Reflecting these molecular responses, knockdown of RPL27 reduced the migration and invasion abilities of CRC cells. In terms of CSC phenotypic changes, RPL27 knockdown suppressed sphere forming capacity of isolated CD133+ CSC population accompanying with the reduction in CD133 and PLK1 levels. Conclusion: Taken together, these findings indicate that RPL27 contributes to promotion of CRC growth and stemness through PLK1 signaling and that targeting RPL27 could be a next-line therapeutic strategy for both primary CRC treatment and prevention of metastasis and/or recurrence. Citation Format: Keon Uk Park, Ilseon Hwang, Hun Mo Ryoo, Yun-Han Lee, So-Young Park. RPL27 augments growth and stemness properties in colorectal cancer through PLK1 signaling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2439.