Klin Padiatr 2020; 232(03): e2
DOI: 10.1055/s-0040-1709765
Abstracts

CD79a/CD79b Promote CNS-Involvement and Leukemic Engraftment in Pediatric B-cell Precursor Acute Lymphoblastic Leukemia

L Lenk
1   Department of Pediatrics, ALL-BFM Study Group, University Medical Center Schleswig-Holstein, Kiel
,
M Carlet
2   Helmholtz Zentrum München, Department of Gene Vectors, Research Center for Environmental Health, Munich, Germany
,
A Cousins
3   Institute of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK
,
G Cario
1   Department of Pediatrics, ALL-BFM Study Group, University Medical Center Schleswig-Holstein, Kiel
,
C Halsey
3   Institute of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK
,
I Jeremias
2   Helmholtz Zentrum München, Department of Gene Vectors, Research Center for Environmental Health, Munich, Germany
,
E Hobeika
4   Institute of Immunology, Ulm University Medical Center, Ulm, Germany
,
H Jumaa
4   Institute of Immunology, Ulm University Medical Center, Ulm, Germany
,
A Alsadeq
4   Institute of Immunology, Ulm University Medical Center, Ulm, Germany
,
DM Schewe
1   Department of Pediatrics, ALL-BFM Study Group, University Medical Center Schleswig-Holstein, Kiel
› Author Affiliations
› Further Information
Also available at
 
 

    Aim To detect novel markers for specific detection and eradication of B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cells in the CNS. Methods: RNA-sequencing with patient derived xenograft (PDX) BCP-ALL cells recovered from CNS versus bone marrow (BM) of NSG-mice was conducted. In vivo engraftment of BCP-ALL cells after knockdown (KD) and antibody (AB)-targeting of candidate molecules CD79a/b was investigated. CD79a/b levels were measured in patient samples and associated with clinical parameters. Results: CD79a/b were significantly upregulated in PDX cells recovered from the CNS versus BM. KD of CD79a in PDX cells resulted in diminished in vivo engraftment in spleen and BM and most markedly in the CNS. Furthermore, absence of CD79a and CD79b in BCR-ABL transformed murine B cells hampered leukemic engraftment. CD79b-AB-therapy significantly reduced CNS-infiltration in xenograft mice. High CD79a/b expression was associated with CNS-infiltration and high CD79a was linked to CNS-relapse in BCP-ALL patients. Conclusion: We suggest CD79a and CD79b as novel markers and potential therapeutic targets for the identification and treatment of CNS-involvement in BCP-ALL.


    #

    Publication History

    Article published online:
    13 May 2020

    © Georg Thieme Verlag KG
    Stuttgart · New York