The long non-coding RNA CDK6-AS1 overexpression impacts on acute myeloid leukemia differentiation and mitochondrial dynamics
Summary: Patients with acute myeloid leukemia (AML) carrying high-risk genetic lesions or high residual disease levels after therapy are particularly exposed to the risk of relapse. Here, we identified the long non-coding RNA CDK6-AS1 able to cluster an AML subgroup with peculiar gene signatures lin...
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2021
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oai:doaj.org-article:093e61aac7c94d7394d6ef693c36724a2021-11-20T05:10:22ZThe long non-coding RNA CDK6-AS1 overexpression impacts on acute myeloid leukemia differentiation and mitochondrial dynamics2589-004210.1016/j.isci.2021.103350https://doaj.org/article/093e61aac7c94d7394d6ef693c36724a2021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2589004221013195https://doaj.org/toc/2589-0042Summary: Patients with acute myeloid leukemia (AML) carrying high-risk genetic lesions or high residual disease levels after therapy are particularly exposed to the risk of relapse. Here, we identified the long non-coding RNA CDK6-AS1 able to cluster an AML subgroup with peculiar gene signatures linked to hematopoietic cell differentiation and mitochondrial dynamics. CDK6-AS1 silencing triggered hematopoietic commitment in healthy CD34+ cells, whereas in AML cells the pathological undifferentiated state was rescued. This latter phenomenon derived from RUNX1 transcriptional control, responsible for the stemness of hematopoietic precursors and for the block of differentiation in AML. By CDK6-AS1 silencing in vitro, AML mitochondrial mass decreased with augmented pharmacological sensitivity to mitochondria-targeting drugs. In vivo, the combination of tigecycline and cytarabine reduced leukemia progression in the AML-PDX model with high CDK6-AS1 levels, supporting the concept of a mitochondrial vulnerability. Together, these findings uncover CDK6-AS1 as crucial in myeloid differentiation and mitochondrial mass regulation.Elena PorcùMaddalena BenettonValeria BisioAmbra Da RosClaudia TregnagoGiulia BorellaCarlo ZanonMatteo BordiGiuseppe GermanoSabrina ManniSilvia CampelloDinesh S. RaoFranco LocatelliMartina PigazziElsevierarticleMolecular biologyCell biologyCancerScienceQENiScience, Vol 24, Iss 11, Pp 103350- (2021) |
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Molecular biology Cell biology Cancer Science Q Elena Porcù Maddalena Benetton Valeria Bisio Ambra Da Ros Claudia Tregnago Giulia Borella Carlo Zanon Matteo Bordi Giuseppe Germano Sabrina Manni Silvia Campello Dinesh S. Rao Franco Locatelli Martina Pigazzi The long non-coding RNA CDK6-AS1 overexpression impacts on acute myeloid leukemia differentiation and mitochondrial dynamics |
| description |
Summary: Patients with acute myeloid leukemia (AML) carrying high-risk genetic lesions or high residual disease levels after therapy are particularly exposed to the risk of relapse. Here, we identified the long non-coding RNA CDK6-AS1 able to cluster an AML subgroup with peculiar gene signatures linked to hematopoietic cell differentiation and mitochondrial dynamics. CDK6-AS1 silencing triggered hematopoietic commitment in healthy CD34+ cells, whereas in AML cells the pathological undifferentiated state was rescued. This latter phenomenon derived from RUNX1 transcriptional control, responsible for the stemness of hematopoietic precursors and for the block of differentiation in AML. By CDK6-AS1 silencing in vitro, AML mitochondrial mass decreased with augmented pharmacological sensitivity to mitochondria-targeting drugs. In vivo, the combination of tigecycline and cytarabine reduced leukemia progression in the AML-PDX model with high CDK6-AS1 levels, supporting the concept of a mitochondrial vulnerability. Together, these findings uncover CDK6-AS1 as crucial in myeloid differentiation and mitochondrial mass regulation. |
| format |
article |
| author |
Elena Porcù Maddalena Benetton Valeria Bisio Ambra Da Ros Claudia Tregnago Giulia Borella Carlo Zanon Matteo Bordi Giuseppe Germano Sabrina Manni Silvia Campello Dinesh S. Rao Franco Locatelli Martina Pigazzi |
| author_facet |
Elena Porcù Maddalena Benetton Valeria Bisio Ambra Da Ros Claudia Tregnago Giulia Borella Carlo Zanon Matteo Bordi Giuseppe Germano Sabrina Manni Silvia Campello Dinesh S. Rao Franco Locatelli Martina Pigazzi |
| author_sort |
Elena Porcù |
| title |
The long non-coding RNA CDK6-AS1 overexpression impacts on acute myeloid leukemia differentiation and mitochondrial dynamics |
| title_short |
The long non-coding RNA CDK6-AS1 overexpression impacts on acute myeloid leukemia differentiation and mitochondrial dynamics |
| title_full |
The long non-coding RNA CDK6-AS1 overexpression impacts on acute myeloid leukemia differentiation and mitochondrial dynamics |
| title_fullStr |
The long non-coding RNA CDK6-AS1 overexpression impacts on acute myeloid leukemia differentiation and mitochondrial dynamics |
| title_full_unstemmed |
The long non-coding RNA CDK6-AS1 overexpression impacts on acute myeloid leukemia differentiation and mitochondrial dynamics |
| title_sort |
long non-coding rna cdk6-as1 overexpression impacts on acute myeloid leukemia differentiation and mitochondrial dynamics |
| publisher |
Elsevier |
| publishDate |
2021 |
| url |
https://doaj.org/article/093e61aac7c94d7394d6ef693c36724a |
| work_keys_str_mv |
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