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Multi-omic profiling of the leukemic microenvironment shows bone marrow interstitial fluid is distinct from peripheral blood plasma Nierves, Lorenz; Guo, Jian; Chen, Siyuan; Tsui, Janice; Uzozie, Anuli C.; Bush, Jonathan W.; Huan, Tao; Lange, Philipp F.

Abstract

Background The bone marrow is the place of hematopoiesis with a microenvironment that supports lifelong maintenance of stem cells and high proliferation. It is not surprising that this environment is also favourable for malignant cells emerging in the bone marrow or metastasizing to it. While the cellular composition of the bone marrow microenvironment has been extensively studied, the extracellular matrix and interstitial fluid components have received little attention. Since the sinusoids connect the bone marrow interstitial fluid to the circulation, it is often considered to have the same composition as peripheral blood plasma. Stark differences in the cellular composition of the bone marrow and peripheral blood with different secretory capacities would however suggest profound differences. Methods In this study we set out to better define if and how the bone marrow interstitial fluid (BMIF) compares to the peripheral blood plasma (PBP) and how both are remodeled during chemotherapy. We applied a multi-omic strategy to quantify the metabolite, lipid and protein components as well as the proteolytic modification of proteins to gain a comprehensive understanding of the two compartments. Results We found that the bone marrow interstitial fluid is clearly distinct from peripheral blood plasma, both during active pediatric acute lymphoblastic leukemia and following induction chemotherapy. Either compartment was shaped differently by active leukemia, with the bone marrow interstitial fluid being rich in extracellular vesicle components and showing protease dysregulation while the peripheral blood plasma showed elevation of immune regulatory proteins. Following chemotherapy, the BMIF showed signs of cellular remodeling and impaired innate immune activation while the peripheral blood plasma was characterized by restored lipid homeostasis. Conclusion This study provides a comprehensive examination of the fluid portion of the acute lymphoblastic leukemia microenvironment and finds the contribution of either microenvironment to tumourigenesis.

Item Metadata

Title
Multi-omic profiling of the leukemic microenvironment shows bone marrow interstitial fluid is distinct from peripheral blood plasma
Creator
Nierves, Lorenz; Guo, Jian; Chen, Siyuan; Tsui, Janice; Uzozie, Anuli C.; Bush, Jonathan W.; Huan, Tao; Lange, Philipp F.
Contributor
Michael Cuccione Childhood Cancer Research Program; Children's Hospital (Vancouver, B.C.). Research Institute.
Publisher
BioMed Central
Date Issued
2022-09-15
Description
Background The bone marrow is the place of hematopoiesis with a microenvironment that supports lifelong maintenance of stem cells and high proliferation. It is not surprising that this environment is also favourable for malignant cells emerging in the bone marrow or metastasizing to it. While the cellular composition of the bone marrow microenvironment has been extensively studied, the extracellular matrix and interstitial fluid components have received little attention. Since the sinusoids connect the bone marrow interstitial fluid to the circulation, it is often considered to have the same composition as peripheral blood plasma. Stark differences in the cellular composition of the bone marrow and peripheral blood with different secretory capacities would however suggest profound differences. Methods In this study we set out to better define if and how the bone marrow interstitial fluid (BMIF) compares to the peripheral blood plasma (PBP) and how both are remodeled during chemotherapy. We applied a multi-omic strategy to quantify the metabolite, lipid and protein components as well as the proteolytic modification of proteins to gain a comprehensive understanding of the two compartments. Results We found that the bone marrow interstitial fluid is clearly distinct from peripheral blood plasma, both during active pediatric acute lymphoblastic leukemia and following induction chemotherapy. Either compartment was shaped differently by active leukemia, with the bone marrow interstitial fluid being rich in extracellular vesicle components and showing protease dysregulation while the peripheral blood plasma showed elevation of immune regulatory proteins. Following chemotherapy, the BMIF showed signs of cellular remodeling and impaired innate immune activation while the peripheral blood plasma was characterized by restored lipid homeostasis. Conclusion This study provides a comprehensive examination of the fluid portion of the acute lymphoblastic leukemia microenvironment and finds the contribution of either microenvironment to tumourigenesis.
Subject
Acute lymphoblastic leukemia; Microenviroment; Bone marrow interstitial fluid; Peripheral blood plasma
Genre
Article
Type
Text
Language
eng
Date Available
2023-05-26
Provider
Vancouver : University of British Columbia Library
Rights
Attribution 4.0 International (CC BY 4.0)
DOI
10.14288/1.0432707
URI
http://hdl.handle.net/2429/84699
Affiliation
Medicine, Faculty of; Science, Faculty of; Non UBC; Chemistry, Department of; Pathology and Laboratory Medicine, Department of
Citation
Experimental Hematology & Oncology. 2022 Sep 15;11(1):56
Publisher DOI
10.1186/s40164-022-00310-0
Peer Review Status
Reviewed
Scholarly Level
Faculty; Researcher
Copyright Holder
The Author(s)
Rights URI
http://creativecommons.org/licenses/by/4.0/
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Attribution 4.0 International (CC BY 4.0)