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Background: CD300s are a group of proteins playing vital roles in immune responses. However, much is yet to be elucidated regarding the expression patterns and clinical significances of CD300s in cancers. Methods: In this study, we comprehensively investigated CD300s in a pan‐cancer manner using multi‐omic data from The Cancer Genome Atlas. We also studied the relationship between CD300s and the immune landscape of AML. Results: We found that CD300A‐CD300LF were generally overexpressed in tumors (especially AML), whereas CD300LG was more often downregulated. In AML, transactivation of CD300A was not mediated by genetic alterations but by histone modification. Survival analyses revealed that high CD300A‐CD300LF expression predicted poor outcome in AML patients; the prognostic value of CD300A was validated in seven independent datasets and a meta dataset including 1115 AML patients. Furthermore, we demonstrated that CD300A expression could add prognostic value in refining existing risk models in AML. Importantly, CD300A‐CD300LF expression was closely associated with T‐cell dysfunction score and could predict response to AML immunotherapy. Also, CD300A was found to be positively associated with HLA genes and critical immune checkpoints in AML, such as VISTA, CD86, CD200R1, Tim‐3, and the LILRB family genes. Conclusions: Our study demonstrated CD300s as potential prognostic biomarker and an ideal immunotherapy target in AML, which warrants future functional and clinical studies. [ABSTRACT FROM AUTHOR]

Epigenetic inactivation of GPX3 has been identified in various cancers including leukemia. Moreover, aberrant DNA methylation was also found as a dominant mechanism of disease progression in myelodysplastic syndrome ( MDS). This study intended to explore GPX3 promoter methylation and its clinical relevance in 110 patients with MDS. GPX3 methylation was examined by real-time quantitative methylation-specific PCR ( RQ- MSP) and bisulfite sequencing PCR ( BSP). GPX3 methylation was identified in 15% (17/110) MDS patients, and significantly higher than controls, and lower than acute myeloid leukemia ( AML) patients ( P = 0.024 and 0.041). GPX3 methylated patients had older age and higher frequency of DNMT3A mutation ( P = 0.015 and 0.066). Cases with GPX3 methylation showed significantly shorter overall survival ( OS) time than those with GPX3 unmethylation analyzed with Kaplan-Meier analysis ( P = 0.012). Moreover, Cox regression analysis revealed that GPX3 methylation might act as an independent prognostic indicator in MDS ( HR = 1.847, P = 0.072). GPX3 methylation density was significantly increased during the progression from MDS to secondary acute myeloid leukemia ( sAML) in three follow-up paired patients. Our study concludes that GPX3 methylation in bone marrow is associated with adverse prognosis and leukemia transformation in MDS. [ABSTRACT FROM AUTHOR]