Aging and comprehensive molecular profiling in acute myeloid leukemia

Area of Science:

• Hematology
• Oncology
• Genomics

Background:

• Acute myeloid leukemia (AML) is a heterogeneous cancer linked to aging.
• Understanding molecular drivers in AML is crucial for prognosis.

Purpose of the Study:

• To analyze the correlation between aging-related factors (age, clonal hematopoiesis), gender, and molecular profiles in AML.
• To identify distinct molecular subgroups within AML based on genetic mutations.

Main Methods:

• Systematic analysis of RNA sequencing and targeted/whole exome sequencing data from 1,474 newly diagnosed AML patients.
• Correlation analysis of aging factors, gender, gene fusions, mutations, and gene expression networks.
• Identification of AML subgroups based on clonal hematopoiesis (CH) and myelodysplastic syndromes (MDS) related mutations.

Main Results:

• AML patients aged 60+ exhibited a significantly worse prognosis.
• Older age correlated with decreased gene fusions and increased CH-related mutations.
• Three distinct subgroups were identified in gene fusion-negative AML: CH-AML, CH-MDS-AML, and other GF- AML.
• CH-MDS-AML subgroup showed a prevalence of elderly males, cytopenia, and adverse outcomes.
• Gene expression networks involving HOXA/B, platelet factors, and inflammatory responses were associated with aging and poor prognosis.

Conclusions:

• Aging, gender, and molecular characteristics significantly influence AML heterogeneity and prognosis.
• Identification of novel AML subgroups (CH-AML, CH-MDS-AML) provides insights into disease mechanisms.
• Gene expression patterns offer potential therapeutic targets for aging-related AML.