AML is the most common type of acute leukemia in adults, and its prevalence and mortality are increasing worldwide due to its unclear pathogenesis and complex genetic mutations that affect clinical prognosis and provide potential targets for drug development [20]. Early detection and risk stratification are essential to improve AML outcome[21]. In this study, we first constructed a risk model based on seven IRLs, and preliminarily investigated the possible mechanisms involved in this process. We also sought to explore the relationship between prognostic models that predict prognosis in AML and the immune landscape. Based on the different expressions of immune checkpoint markers and antineoplastic drugs sensitivities, we provide a new insight into AML individualizing therapy.
LncRNA plays an important role in occurrence, development, and prognosis of AML [22]. Among seven lncRNAs in the prognostic risk model, the lncRNA LINC00987 and MIR133A1HG deregulation were demonstrated significantly correlated with prognosis and tumor progression in AML [23, 24], indicated that LINC00987 and MIR133A1HG may serve as new promising individualized therapeutic targets for the treatment of AML [25]. Our data reaffirmed its potential value as therapeutic targets in AML. NORAD is a newly characterized lncRNA activated by DNA damage and implicated in maintaining genomic stability and regular mitosis [26]. In non-M3 AML patients, upregulation of NORAD was illustrated significantly associated with poor overall survival and unfavorable cytogenetic risk[27]. However, the underlying mechanism of NORAD has not been fully clarified, and more studies are urgently needed to comprehensive explore precise molecular mechanisms. The expression pattern, clinical relevance and underlying mechanisms of AC244502.1, AFF2 − IT1, AL5924292 and AC022182.2 in AML patients is still poorly understood which need further validation in the future.
Immune regulation is markedly involved in progression and clinical outcomes of AML. Therefore, the use of immunotherapy to produce an effective immune response to the tumor to delay the development of cancer is considered to be effective in AML [28]. The number and proportion of infiltrating immune cells are regarded as important factors affecting cancer development and immunotherapy response and closely related to patient outcomes [29]. In our results, immunosuppressive cell types such as Treg and MDSCs were significantly increased in high-risk AML group, which could generate the
immunosuppressive tumor microenvironment[30, 31]. Treg-mediated immune-suppression plays critical part in tumor immune evasion, may be responsible for the incidence and development of AML [32, 33]. MDSCs, as a significant role in tumor progression, is corelated with poor outcome and decreased efficiency of immunotherapy [34]. MDSCs mediated immunosuppression can contribute to immune evasion by depleting necessary nutrients for lymphocytes to function, inhibiting T cell proliferation and survival via generation of oxidative stress[35]. The above results suggested that the higher immunosuppression in the tumor microenvironment of high-risk patients contribute to tumor progression and poorer prognosis and response of immunotherapy. In addition, TIDE analysis between different groups was utilized to evaluate the response of immunotherapy [36]. The higher the TIDE score is more frequently associated with immune escape, which may suggest a limited response and shorter survival time for patients treated with immune checkpoint inhibitors [37]. The low-risk group show a better potential immunotherapy response, which is in line with previous report. The influence of ICD classification on prognosis was explained by combining with the significance of immunotherapy in clinical application.
In conclusion, we successfully constructed a predictive signature in AML based on seven IRLs, which may offer novel perspectives in seeking immunotherapy for AML patients. Meanwhile, we believe that these findings will increase the understanding about ICD and have the potential to promote more individual and precise therapeutic treatment in AML.