Klin Padiatr 2022; 234(03): 176
DOI: 10.1055/s-0042-1748686
Abstracts

A meningeal preleukemic niche promotes the homing of B-cell Precursor Acute Lymphoblastic Leukaemia cells to the CNS

A Mayar
1   Department of Pediatrics, ALL-BFM Study Group, University Medical Center Schleswig-Holstein, Kiel, Germany
,
O Ibuli
2   Center for Molecular Medicine Cologne, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany
,
M Bultmann
3   Medical Department II, Hematology and Oncology, University Medical Center Schleswig-Holstein, Kiel, Germany
,
D Winterberg
1   Department of Pediatrics, ALL-BFM Study Group, University Medical Center Schleswig-Holstein, Kiel, Germany
,
I Jeremias
4   Research Unit Apoptosis in Hematopoietic Stem Cells, Helmholtz Zentrum München, German Center or Environmental Health (HMGU), Munich, Germany
,
A Dietterle
1   Department of Pediatrics, ALL-BFM Study Group, University Medical Center Schleswig-Holstein, Kiel, Germany
,
G Münch
1   Department of Pediatrics, ALL-BFM Study Group, University Medical Center Schleswig-Holstein, Kiel, Germany
,
L Bastian
3   Medical Department II, Hematology and Oncology, University Medical Center Schleswig-Holstein, Kiel, Germany
,
D M Schewe
5   Department of Pediatrics, Otto-von-Guericke-University, Magdeburg, Germany
,
L Lenk
1   Department of Pediatrics, ALL-BFM Study Group, University Medical Center Schleswig-Holstein, Kiel, Germany
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Correction: A meningeal preleukemic niche promotes the homing of B-cell Precursor Acute Lymphoblastic Leukaemia cells to the CNSKlin Padiatr 2022; 234(03): e1-e1
DOI: 10.1055/a-1871-5731

Aim To understand early events promoting the engraftment and homing of BCP-ALL cells to the CNS in order to identify potential therapeutic interventions.

Methods We determined in vivo engraftment kinetics of luciferase+ BCP-ALL patient derived xenograft (PDX) cells in NSG-mice and subjected healthy vs pre-leukemic meninges to RNA-sequencing. Potential preleukemic niche (PLN) associated factors were validated in vitro using CRISPR-CAS9 editing of CNS “stroma” cell lines in CNS/ALL-cocultures.

Results Comparative RNA-sequencing showed an upregulation of inflammation and adhesion pathways and molecules previously shown to be associated with CNS-leukemia (e.g. IL7, CXCL12) in preleukemic meninges. In vitro coculture of the CNS-tropic cell lines REH and NALM6 with BEND3, BMEC cells and primary murine meningeal fibroblasts resulted in a significant upregulation of VCAM1 in the CNS stroma. Knockdown of VCAM1 in CNS cells resulted in a reduced release of proinflammatory chemokines in cocultures.

Conclusion BCP-ALL cells may induce alterations in murine meninges promoting a PLN in the CNS. This may open the window for novel targeted interventions and early diagnosis in CNS-leukemia.



Publication History

Article published online:
17 May 2022

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