AML patient blasts exhibit polarization defects upon interaction with bone marrow stromal cells

Area of Science:

• Hematology
• Cancer Biology
• Cell Biology

Background:

• Hematopoietic stem and progenitor cells (HSPCs) normally polarize within their bone marrow niche.
• Cell polarity is crucial for preventing cancer development.
• The bone marrow niche plays a significant role in acute myeloid leukemia (AML) progression.

Purpose of the Study:

• To investigate the cell polarization capacity of leukemic blasts in AML.
• To determine the influence of the bone marrow niche on leukemic cell polarization.

Main Methods:

• Utilized engineered micro-niches to model the bone marrow microenvironment.
• Assessed cell polarization by measuring centrosome position relative to stromal cell contact sites.
• Co-cultured AML cell lines and primary AML patient cells with healthy and patient-derived stromal cells.

Main Results:

• AML cell lines and primary AML blasts failed to polarize when interacting with healthy stromal cells.
• Exposure to stromal cells derived from AML patients impaired the polarization of both healthy HSPCs and AML blasts.
• Stromal cells from a leukemic niche promoted the migration of healthy HSPCs and AML blasts in a "bone-marrow-on-a-chip" model.

Conclusions:

• Leukemic blasts exhibit intrinsic defects in cell polarization.
• The bone marrow microenvironment in AML can be transformed, further compromising leukemic cell polarization.
• Both intrinsic transformation and extrinsic niche interactions negatively impact AML blast polarization, highlighting the complex interplay in leukemia progression.