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Peer-reviewedCC BY 4.0Communications Medicine

Disruption of marrow microenvironments in chronic lymphocytic leukemia by high-resolution synchrotron micro-computed tomography

Abstract

Background: Chronic lymphocytic leukemia (CLL) is associated with increased fracture risk unexplained by standard bone density scans, suggesting underlying microstructural alterations. Whether leukemic infiltration disrupts the bone marrow microenvironment at the structural level remains poorly understood.

Methods: We used high-resolution synchrotron micro-computed tomography (SR μ CT) on bone marrow biopsies from 17 CLL patients, stratified into low and high infiltration groups using objective, data-driven k-means clustering. Osteocyte lacunar density and intertrabecular marrow surface area-to-volume ratio (SA:V) were quantified using image processing and deep learning segmentation. Sensitivity analyses adjusting for prior therapy were performed using linear regression.

Results: Here we show that high CLL marrow infiltration is associated with a 40.3% reduction in lacunar density and a 101% increase in normalized intertrabecular marrow SA:V, a metric reflecting greater structural fragmentation of the marrow compartment. Both changes correlate with leukemic infiltration percentage and show partial reversal after therapy in a longitudinal case.

Conclusions: We identify a marrow remodeling phenotype in CLL characterized by osteocyte depletion and intertrabecular marrow disruption. These changes likely contribute to skeletal fragility and represent potential microstructural biomarkers for assessing marrow health more accurately than conventional imaging.

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BibTeX
@article{lee2026disruption,
  title = {{Disruption of marrow microenvironments in chronic lymphocytic leukemia by high-resolution synchrotron micro-computed tomography}},
  author = {In Kyu Lee and Yoshihiro Obata and Anthony D. Pomicter and Justin A. Williams and Bejal Kikani and Christopher E. Jensen and Douglas W. Sborov and Deborah M. Stephens and Claire Acevedo},
  journal = {Communications Medicine},
  year = {2026},
  month = oct,
  doi = {10.1038/s43856-026-01945-4},
  url = {https://www.nature.com/articles/s43856-026-01945-4},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Disruption of marrow microenvironments in chronic lymphocytic leukemia by high-resolution synchrotron micro-computed tomography
AU  - In Kyu Lee
AU  - Yoshihiro Obata
AU  - Anthony D. Pomicter
AU  - Justin A. Williams
AU  - Bejal Kikani
AU  - Christopher E. Jensen
AU  - Douglas W. Sborov
AU  - Deborah M. Stephens
AU  - Claire Acevedo
PY  - 2026
DA  - 2026/10/21
JO  - Communications Medicine
DO  - 10.1038/s43856-026-01945-4
UR  - https://www.nature.com/articles/s43856-026-01945-4
AB  - Background: Chronic lymphocytic leukemia (CLL) is associated with increased fracture risk unexplained by standard bone density scans, suggesting underlying microstructural alterations. Whether leukemic infiltration disrupts the bone marrow microenvironment at the structural level remains poorly understood.  Methods: We used high-resolution synchrotron micro-computed tomography (SR μ CT) on bone marrow biopsies from 17 CLL patients, stratified into low and high infiltration groups using objective, data-driven k-means clustering. Osteocyte lacunar density and intertrabecular marrow surface area-to-volume ratio (SA:V) were quantified using image processing and deep learning segmentation. Sensitivity analyses adjusting for prior therapy were performed using linear regression.  Results: Here we show that high CLL marrow infiltration is associated with a 40.3% reduction in lacunar density and a 101% increase in normalized intertrabecular marrow SA:V, a metric reflecting greater structural fragmentation of the marrow compartment. Both changes correlate with leukemic infiltration percentage and show partial reversal after therapy in a longitudinal case.  Conclusions: We identify a marrow remodeling phenotype in CLL characterized by osteocyte depletion and intertrabecular marrow disruption. These changes likely contribute to skeletal fragility and represent potential microstructural biomarkers for assessing marrow health more accurately than conventional imaging.
SN  - 2730-664X
ER  -