Key molecular pathways associated with therapy resistance in AML

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy characterized by the rapid proliferation of immature myeloid cells in the bone marrow, leading to impaired hematopoiesis and life-threatening complications. Despite advances in chemotherapy, targeted therapy, and stem cell transplantation, treatment resistance remains a major clinical challenge, contributing to high relapse rates and poor survival outcomes. Understanding the mechanisms of resistance — including genetic mutations, epigenetic alterations, and microenvironmental interactions — is crucial for developing more effective therapies. Investigating how AML cells develop treatment resistance, particularly under pro-inflammatory conditions, may reveal novel therapeutic targets and improve patient prognosis. Our study focuses on resistance mechanisms in AML cells under density-induced sterile pro-inflammatory conditions (modelled via high-density culture, HDC). This approach aims to identify key molecular pathways associated with therapy resistance in AML. Comparison of RNA-seq profiles between: (1) AML THP-1 cells under high-density culture (HDC; reversible therapy resistance via sterile pro-inflammatory signaling), (2) AML THP-1 cells under low-density culture (LDC; non-inflammatory condition), and (3) mutant macrophage-like AML THP-1 (THP-1ad) cells derived from HDC (exhibiting fully resistant, differentiated phenotype)