Disruption of Marrow Microenvironments in Chronic Lymphocytic Leukemia by High-Resolution Synchrotron Micro-Computed...

Area of Science:

• Biomedical Engineering
• Hematology
• Skeletal Biology

Background:

• Chronic lymphocytic leukemia (CLL) is linked to increased fracture risk.
• Standard bone density scans do not fully explain this heightened skeletal fragility.
• Underlying microstructural bone alterations are suspected in CLL patients.

Purpose of the Study:

• To investigate the microstructural bone marrow changes associated with chronic lymphocytic leukemia.
• To quantify the impact of CLL infiltration on bone marrow microstructure.
• To identify potential microstructural biomarkers for skeletal health in CLL.

Main Methods:

• High-resolution synchrotron micro-computed tomography (SRμCT) was used on bone marrow biopsies from 17 CLL patients.
• Patients were stratified into low and high CLL infiltration groups.
• Lacuna density, adipose surface area-to-volume ratio, and osteocyte morphology were quantified.

Main Results:

• High CLL marrow infiltration correlated with a 40.3% reduction in lacuna density.
• A 101% increase in normalized adipose surface area-to-volume ratio indicated greater structural fragmentation.
• Significant alterations in osteocyte morphology were observed in high infiltration groups (p < 0.001).

Conclusions:

• A novel marrow remodeling phenotype in CLL is characterized by osteocyte depletion and adipose disruption.
• These microstructural changes likely contribute to skeletal fragility in CLL patients.
• The identified changes may serve as potential microstructural biomarkers for assessing marrow health.