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| Status |
Public on Feb 29, 2020 |
| Title |
Inflammation favors the emergence of ETV6-RUNX1-positive pre-leukemic cells in a model of mesenchymal niche |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
ETV6-RUNX1 (E/R) fusion gene, arising in utero from t(12;21), is the most frequent alteration in childhood acute lymphoblastic leukemia (ALL). Despite this, E/R is insufficient to overt disease since it generates a clinically silent pre-leukemic clone which contributes to hematopoiesis but fail to out-compete normal hematopoietic progenitors. Conversely, pre-leukemic cells show increased susceptibility to malignant transformation following additional genetic insults. Infections/inflammation are the most accredited triggers for mutations accumulation and progression in E/R+ pre-leukemic cells. However, how E/R and inflammation interact in promoting leukemia, both directly or through other cellular components in the bone marrow (BM) niche, is still poorly understood. Here, we demonstrate that IL6/TNFα/ILβ pro-inflammatory cytokines cooperate with BM-MSC in promoting the emergence of E/R+ murine pro-B cells over their normal counterparts by differentially affecting their proliferation, survival and migration. Very interesting, E/R-expressing human CD34+IL7R+ progenitors, a candidate population for pre-leukemic initiation during development, were preserved within the inflamed niche compared to their normal counterparts. Finally, the extent of DNA damage and activation-induced cytidine deaminase (AID) expression increase within the inflamed niche in both cell type, potentially leading to transformation in the apoptosis-resistant pre-leukemic clone. Overall, our data provide new mechanistic insights in childhood ALL pathogenesis.
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| Overall design |
Gene expression was measured on GeneChip Mouse 2.0 platform of cells derived from BaF3 cells with TEL_AML1 fusion trascript and from wild type BaF3 cells.
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| Contributor(s) |
Bresolin S, Palmi C |
| Citation missing |
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| |
| Submission date |
Jul 17, 2019 |
| Last update date |
Mar 02, 2020 |
| Contact name |
silvia bresolin |
| E-mail(s) |
silvia.bresolin@unipd.it
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| Phone |
+390498215487
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| Organization name |
università di padova
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| Department |
department of women's and children's health
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| Lab |
SSD ematologia-clinica sperimentale
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| Street address |
via giustiniani 3
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| City |
padova |
| State/province |
padova |
| ZIP/Postal code |
35128 |
| Country |
Italy |
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| Platforms (1) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA558759 |
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