Activin A contributes to the definition of a pro-oncogenic bone marrow microenvironment in t(12;21) preleukemia.
Activins
/ genetics
Bone Marrow
/ metabolism
Cell Line
Chemokine CXCL12
/ genetics
Chromosomes, Human, Pair 12
/ genetics
Chromosomes, Human, Pair 21
/ genetics
Core Binding Factor Alpha 2 Subunit
/ genetics
Humans
Leukemia
/ genetics
Mesenchymal Stem Cells
/ metabolism
Oncogene Proteins, Fusion
/ genetics
Precancerous Conditions
/ genetics
Stem Cell Niche
Translocation, Genetic
Journal
Experimental hematology
ISSN: 1873-2399
Titre abrégé: Exp Hematol
Pays: Netherlands
ID NLM: 0402313
Informations de publication
Date de publication:
05 2019
05 2019
Historique:
received:
20
12
2018
revised:
11
02
2019
accepted:
24
02
2019
pubmed:
3
3
2019
medline:
19
2
2020
entrez:
3
3
2019
Statut:
ppublish
Résumé
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 β (TGF-β), can further accelerate this process by creating a protumoral bone marrow (BM) microenvironment. Here, we show that activin A, a member of the TGF-β 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-β, could play an important role in the creation of a pro-oncogenic BM microenvironment and provide novel mechanistic insights into TEL-AML1-associated leukemogenesis.
Identifiants
pubmed: 30825516
pii: S0301-472X(19)30079-7
doi: 10.1016/j.exphem.2019.02.006
pii:
doi:
Substances chimiques
CXCL12 protein, human
0
Chemokine CXCL12
0
Core Binding Factor Alpha 2 Subunit
0
Oncogene Proteins, Fusion
0
TEL-AML1 fusion protein
0
activin A
0
Activins
104625-48-1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
7-12.e4Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL103726
Pays : United States
Informations de copyright
Copyright © 2019. Published by Elsevier Inc.