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Role of the desmosomal adhesion molecule desmoglein-2 in acute lymphoblasic leukemia
Third-party funded project
Project title Role of the desmosomal adhesion molecule desmoglein-2 in acute lymphoblasic leukemia
Principal Investigator(s) Schinner, Camilla
Organisation / Research unit Departement Biomedizin / Cell Adhesion (Spindler)
Project start 01.02.2020
Probable end 31.01.2021
Status Completed
Abstract

Acute lymphoblastic leukemia (ALL) is the most frequent malignancy in childhood with exceptionally
high frequency in Mexico City (1, 2). It is characterized by hyper-proliferation and accumulation of
lymphoid progenitor cells in the bone marrow and blood with invasion into other tissues during
progression of disease (3, 4). Even though pediatric ALL has a high survival rate, relapsed disease,
organ infiltration or disease onset during adolescence are challenging to be treated effectively. This
highlights the importance of a better understanding of the disease mechanisms. Our preliminary data
uncovered a hitherto unknown expression of the desmosomal adhesion molecule desmoglein-2
(DSG2) in two ALL cell lines (Jurkat T-ALL and REH B-ALL), while primary human lymphocytes do
not express this protein under baseline condition but during proliferation after PHA stimulation.
Importantly, reduction of DSG2 expression by shRNA significantly impaired Jurkat cell viability,
suggesting a role of DSG2 in leukemia progression. In the proposed project, the malignant potential
of DSG2-deficient ALL cell lines will be clarified by applying these cells in transendothelial migration
assays, 3D bone marrow organoid colonization, and in vivo xenograft mouse model. Furthermore,
samples from ALL patients affected by different subtypes will be screened for DSG2 expression
compared to healthy controls. In these samples, DSG2 protein levels will be reduced by lentivirally
delivered shDSG2. The effect of DSG2 depletion on lymphoblast function will be determined with a
focus on the contribution to cell proliferation, adhesion and infiltration. With this proposal we will
combine the knowledge of a Mexico-based immunobiology laboratory and an associated
oncoimmunology group with access to patient samples and expertise in ALL and leukemia mouse
models with a Swiss cell adhesion research group with focus on function of desmosomal molecules.
This collaboration includes exchange of scientists, samples, material and expertise. We are convinced
that the proposed experiments will clarify a possible contribution of DSG2 during ALL progression.
Our data may provide novel insights into the mechanisms underlying the pathogenesis of ALL and
potentially identify novel treatment approaches.

Financed by Swiss Government (Research Cooperations)
   

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