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Updated: Feb 4, 2026
06:48
In Ovo Xenografting of Patient-Derived Acute Lymphoblastic Leukemia (ALL) Cells (PDX-ALL)
Published on: August 1, 2025
533
ActivinA: a new leukemia-promoting factor conferring migratory advantage to B-cell precursor-acute lymphoblastic
Federica Portale1, Giulia Cricrì1, Silvia Bresolin2
1Centro Ricerca Tettamanti, Department of Pediatrics, University of Milano-Bicocca, Fondazione MBBM, Monza.
Haematologica
|September 29, 2018
Summary
ActivinA is over-expressed in leukemia and promotes cancer cell migration and bone marrow engraftment. This protein enhances leukemia progression by reprogramming the bone marrow microenvironment, offering a potential therapeutic target.
Area of Science:
- Hematology
- Oncology
- Cell Biology
Background:
- B-cell precursor-acute lymphoblastic leukemia (B-ALL) alters the bone marrow (BM) niche, creating a leukemia-supportive and chemo-protective microenvironment.
- Targeting the leukemia-stroma interplay is crucial for improving B-ALL treatment outcomes.
Purpose of the Study:
- To identify novel factors involved in leukemia-stroma interactions within the BM niche.
- To investigate the role of ActivinA, a TGF-β family member, in B-ALL pathogenesis and its potential as a therapeutic target.
Main Methods:
- Quantification of ActivinA expression in leukemic and normal BM samples.
- In vitro culture of leukemic cells with mesenchymal stromal cells (MSCs).
- Analysis of leukemic cell motility and migration pathways.
- Assessment of intracellular calcium levels and actin polymerization.
- In vivo validation using a xenograft mouse model.
Main Results:
- ActivinA is over-expressed in leukemic BM and its production is induced in MSCs cultured with leukemic cells.
- Leukemic MSCs intrinsically secrete higher levels of ActivinA compared to normal MSCs.
- ActivinA enhances leukemic cell motility, CXCL12-driven migration, and invasiveness.
- ActivinA selectively increases intracellular calcium and actin polymerization in leukemic cells, impairing healthy cell migration.
- ActivinA promotes BM engraftment and metastatic potential in a mouse model.
Conclusions:
- ActivinA is a key leukemia-promoting factor that confers a migratory advantage to leukemic cells within the BM niche.
- The pro-inflammatory leukemic BM microenvironment synergizes with leukemic cells to induce stromal ActivinA production.
- ActivinA represents a promising therapeutic target for B-ALL by disrupting leukemia-stroma interactions and enhancing disease progression.
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