High-density cultures (3D-cultures) associated therapy resistance in AML THP-1 cells

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. Overall design: 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)