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| Status |
Public on Apr 03, 2023 |
| Title |
Long-term proliferation of immature hypoxia-dependent JMML cells supported by a 3D in vitro system |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Juvenile myelomonocytic leukemia (JMML) is a rare stem cell disorder occurring in early childhood and characterized by RAS pathway hyperactivation in 95% of patients. JMML is identified by a hyperproliferation of granulocyte and monocyte, and little is known about the heterogeneous nature of leukemia initiating cells as well as the cellular hierarchy of the JMML bone marrow (BM). In this study, we reported the generation and characterization of a novel patient-derived 3D in vitro JMML model (pd-JAO) sustaining long-term proliferation of JMML cells with stem cell features and patient specific hallmarks. JMML cells brewed in the 3D model under different microenvironmental conditions acquired a proliferative and survival advantage when placed at low oxygen tensions. Transcriptomic and microscopic analysis revealed the activation of specific metabolic energy pathways and the inactivation of processes leading to cell death. Furthermore, we demonstrated pd-JAO derived cells’ migratory, propagation and self-renewal capacities both in in vitro and in vivo mouse model. Our study contributed to the development of a robust JMML 3D in vitro model to study and comprehend the impact of microenvironment stimuli on JMML disease and the molecular mechanisms regulating JMML initiating and propagating cells. Pd-JAO may become a promising model for compound tests focusing on new therapeutic intervention aiming to eradicate JMML progenitors and control JMML disease.
We defined a 3D in vitro model that under hypoxic conditions is able to sustain long-term propagation of JMML-patients cells with specific hallmarks. Different oxygen level enviroment drive specific metabolic switch that prompts JMML cells to self-renewal.
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| Overall design |
Gene expression was measured using Affymetrix platform in pairs of primary JMML pd-JAO derived cells maintained both in hypoxia and normoxia conditions
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| Contributor(s) |
Bresolin S |
| Citation(s) |
36053787 |
| |
| Submission date |
Nov 11, 2021 |
| Last update date |
May 12, 2023 |
| Contact name |
silvia bresolin |
| E-mail(s) |
silvia.bresolin@unipd.it
|
| Phone |
+390498215487
|
| Organization name |
università di padova
|
| Department |
department of women's and children's health
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| Lab |
SSD ematologia-clinica sperimentale
|
| Street address |
via giustiniani 3
|
| City |
padova |
| State/province |
padova |
| ZIP/Postal code |
35128 |
| Country |
Italy |
| |
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| Platforms (1) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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| Samples (10)
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| Relations |
| BioProject |
PRJNA779629 |
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