Abstract
Recent studies have demonstrated epigenetic regulation of immune responses. Nevertheless, the underlying effect of RNA N6-methyladenosine (m6A) modifications on tumor microenvironment cell infiltration remains elusive. In this study, we thoroughly assessed m6A modification patterns of 255 myeloid leukemia specimens based on 23 m6A regulators. Consensus clustering of the 23 m6A regulators was performed to determine three distinct m6A modification patterns that were remarkably consistent with three immunophenotypes of tumors: immunorejection, immune activation, and immune inertness. Further evaluation and prognostic analysis of the m6A modification patterns of individual tumors revealed that low m6A score was characterized by increased mutational burden, immune activation, and survival rates, whereas high m6A score was characterized by poorer survival rates and the absence of effective immune infiltration. In addition, this study investigated the association between m6A regulators and antitumor immune responses and discovered higher expression of the immune regulators PD-L1, PD-L2, MRP1, and MRP2 in low m6A scores. Generally, the expression pattern of m6A regulators was remarkably associated with prognostic results and antitumor immune responses in acute myeloid leukemia and may be an underlying target and biological marker for immune therapies.
Highlights
Acute myeloid leukemia (AML) is one of the most common and invasive hematological carcinomas in adults, accounting for approximately 1% of all cancers [1, 2]
We revealed three different m6A modification patterns and interestingly discovered that TME features in these three patterns remarkably coincided with immunorejection, immune activation, and immunodeficiency phenotypes, respectively, revealing that m6A modifications have a nonnegligible effect on the formation of different TME features
We first summarized the incidence of copy number variant (CNV) and somatic mutations in 23 m6A regulators in AML, including eight writers, two erasers, and 13 readers (Supplementary Table S2)
Summary
Acute myeloid leukemia (AML) is one of the most common and invasive hematological carcinomas in adults, accounting for approximately 1% of all cancers [1, 2]. AML is characterized by the culmination of immature bone marrow hematopoietic cells, in the bone marrow. The primary treatment strategies for AML, namely, intensive induction chemical therapy and postremission treatment, have remained largely unchanged over the last 30 years, and patient survival has not substantially improved [4, 5]. Despite the fact that substantial studies have assisted in revealing the genomic picture of AML and better comprehending its evolution, converting such knowledge into better therapeutic approaches has just begun. The determination of underlying markers will improve the diagnostic, therapeutic, and prognostic results of patients with acute myeloid leukemia
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