Acute Myeloid Leukemia (AML) is a hematological malignancy of well-recognized clinical and epidemiological relevance, due to its high incidence and mortality rates worldwide. Its pathogenesis involves the uncontrolled proliferation of immature myeloid precursors in the bone marrow, impairing normal hematopoiesis. Recent bioinformatics studies supported by artificial intelligence tools have identified the MICALL2 protein as a promising prognostic marker, given its involvement in cytoskeletal regulation and in cellular processes such as adhesion, migration, metabolism, and intracellular signaling. Although MICALL2 has already been implicated in solid tumor development, its role remains unexplored in hematological malignancies.

In this context, the present study aimed to investigate the functional and prognostic role of the MICALL2 protein in Acute Myeloid Leukemia through bioinformatic analyses applied to transcriptomic data from public databases.

Data from AML patients in the TCGA cohort were analyzed. Samples were dichotomized based on MICALL2 expression levels, with the cut-off defined by ROC curve analysis. Overall survival and disease-free survival were assessed using Kaplan–Meier analysis, and the same stratification was used for gene ontology and enrichment analyses. MICALL2 expression in normal hematopoiesis was investigated using NCBI data and visualized through hierarchical plots generated via the BloodSpot platform.

A correlation was identified between high MICALL2 gene expression and improved overall survival (p = 0.005; HR = 1.90), as well as a higher prevalence of patients classified in the intermediate molecular risk group (p = 0.005; HR = 0.277). Functional analyses revealed that elevated MICALL2 expression is associated with increased activation of pathways related to cell proliferation, energy metabolism, and DNA repair, while repressing signaling and differentiation processes. Significant positive correlations were observed between MICALL2 and genes involved in metabolism and inflammatory response, along with negative correlations with genes related to cellular differentiation, apoptosis, and stress response. Regarding its expression during hematopoiesis, MICALL2 levels were higher in erythroid cells compared to hematopoietic stem cells, while other lineages displayed homogeneous expression profiles.

The association between high MICALL2 expression and favorable prognostic variables in AML suggests a relevant regulatory role within the biological heterogeneity of the disease. Although functionally linked to proliferation, metabolism, and repair pathways, its expression pattern correlates with less aggressive clinical profiles, possibly reflecting cellular states with higher degrees of differentiation or reduced functional plasticity. The increased expression in the erythroid lineage during physiological hematopoiesis reinforces its involvement in specific transcriptional programs, potentially influencing the behavior of distinct leukemic subgroups. These findings support the hypothesis that MICALL2 may serve as a potential prognostic biomarker and underscore the importance of its functional investigation in experimental models to validate its clinical and therapeutic applicability.