Activin A contributes to the definition of a pro-oncogenic bone marrow microenvironment in t(12;21) preleukemia.
Exp Hematol
; 73: 7-12.e4, 2019 05.
Article
in En
| MEDLINE
| ID: mdl-30825516
ABSTRACT
The TEL-AML1 fusion gene, generated by the t(12;21) chromosome translocation, arises in a progenitor/stem cell and could induce clonal expansion of a persistent preleukemic B-cell clone which, on acquisition of secondary alterations, may turn into full-blown leukemia. During infections, deregulated cytokine signaling, including transforming growth factor ß (TGF-ß), can further accelerate this process by creating a protumoral bone marrow (BM) microenvironment. Here, we show that activin A, a member of the TGF-ß family induced under inflammatory conditions, inhibits the proliferation of normal progenitor B cells but not that of preleukemic TEL-AML1-positive clones, thereby providing a selective advantage to the latter. Finally, we find that activin A inhibits BM-derived mesenchymal stromal cell-mediated secretion of CXCL12, a major chemoattractant in the BM compartment, thereby contributing to shape a leukemia-promoting environment. Overall, our findings indicate that activin A, in concert with TGF-ß, could play an important role in the creation of a pro-oncogenic BM microenvironment and provide novel mechanistic insights into TEL-AML1-associated leukemogenesis.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Precancerous Conditions
/
Translocation, Genetic
/
Bone Marrow
/
Chromosomes, Human, Pair 12
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Chromosomes, Human, Pair 21
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Leukemia
/
Activins
/
Stem Cell Niche
/
Mesenchymal Stem Cells
Limits:
Humans
Language:
En
Journal:
Exp Hematol
Year:
2019
Type:
Article
Affiliation country:
Italy