A Focus on Intermediate-Risk Acute Myeloid Leukemia: Sub-Classification Updates and Therapeutic Challenges

Abstract

Acute myeloid leukemia (AML) represents a heterogeneous group of hematopoietic neoplasms deriving from the abnormal proliferation of myeloid progenitors in the bone marrow. Patients with AML may have highly variable outcomes, which are generally dictated by individual clinical and genomic characteristics. As such, the European LeukemiaNet 2017 and 2022 guidelines categorize newly diagnosed AML into favorable-, intermediate-, and adverse-risk groups, based on their molecular and cytogenetic profiles. Nevertheless, the intermediate-risk category remains poorly defined, as many patients fall into this group as a result of their exclusion from the other two. Moreover, further genomic data with potential prognostic and therapeutic influences continue to emerge, though they are yet to be integrated into the diagnostic and prognostic models of AML. This review highlights the latest therapeutic advances and challenges that warrant refining the prognostic classification of intermediate-risk AML.

Keywords: acute myeloid leukemia; intermediate-risk category; rational therapeutic strategies and challenges.

Figure 1

The clinical problem of intermediate-risk AML. The upper panel summarizes features responsible for molecular heterogeneity, and host-related outcome modifiers are summarized. In the lower panel, current research approaches to ameliorating the outcomes of such patients are illustrated. Specifically, the application of genome scanning techniques and machine learning methods may help better characterize AML populations to assess geno-phenotypic associations and identify therapeutic vulnerabilities.