B- and T-cell acute lymphoblastic leukemias evade chemotherapy at distinct sites in the bone marrow
OPEN ACCESS
Loading...
Author / Producer
Date
2023-05
Publication Type
Journal Article
ETH Bibliography
yes
Citations
Altmetric
OPEN ACCESS
Data
Abstract
Persistence of residual disease after induction chemotherapy is a strong predictor of relapse in acute lymphoblastic leukemia (ALL). The bone marrow microenvironment may support escape from treatment. Using three-dimensional fluorescence imaging of ten primary ALL xenografts we identified sites of predilection in the bone marrow for resistance to induction with dexamethasone, vincristine and doxorubicin. We detected B-cell precursor ALL cells predominantly in the perisinusoidal space at early engraftment and after chemotherapy. The spatial distribution of T-ALL cells was more widespread with contacts to endosteum, nestin+ pericytes and sinusoids. Dispersion of T-ALL cells in the bone marrow increased under chemotherapeutic pressure. A subset of slowly dividing ALL cells was transiently detected upon short-term chemotherapy, but not at residual disease after chemotherapy, challenging the notion that ALL cells escape treatment by direct induction of a dormant state in the niche. These lineage-dependent differences point to niche interactions that may be more specifically exploitable to improve treatment.
Permanent link
Publication status
published
External links
Editor
Book title
Journal / series
Volume
108 (5)
Pages / Article No.
1244 - 1258
Publisher
Fondazione Ferrata Storti
Event
Edition / version
Methods
Software
Geographic location
Date collected
Date created
Subject
Organisational unit
03992 - Schroeder, Timm / Schroeder, Timm
Notes
Funding
186271 - Elucidating the human mesenchymal bone marrow stromal hierarchy in health and disease (SNF)