ITGAL infers adverse prognosis and correlates with immunity in acute myeloid leukemia

Abstract

AbstractIntegrin subunit alpha L (ITGAL) was found aberrantly expressed in multiple cancer types, suggesting its essential role in tumorigenesis. Hence, we aimed to explore its definite role in acute myeloid leukemia and emphasize its associations with immunity. Here, we found ITGAL was highly expressed in AML patients and elevated expression was associated with poor prognosis. ITGAL was associated with age and cytogenetic risk classifications, but not relevant to AML driver gene mutations. Univariate and multivariate Cox regression analyses determined ITGAL as an independent prognostic factor. The nomogram integrating ITGAL and clinicopathologic variables was constructed to predict 1-, 3- and 5-year overall survival (OS). Functional analyses revealed that ITGAL was mainly responsible for the production and metabolic process of cytokine. As for immunity, ITGAL was positively associated with MDSCs including iDCs, and macrophages in the TCGA-LAML cohort. We also found that ITGAL was positively associated with most immune checkpoint genes and cytokines. In addition, we found that ITGAL knockdown caused substantial inhibition of cell growth and significant induction of early apoptosis in AML cells. The xenograft study indicated that ITGAL knockdown prolonged the survival of recipient mice. Overall, ITGAL is an independent prognostic factor and is closely related to the number of MDSCs and cytokine production.