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Biochem Biophys Res Commun. 2018 Apr 15;498(4):715-722. doi: 10.1016/j.bbrc.2018.03.023. Epub 2018 Mar 17.

Superoxide dismutase 2 (SOD2) contributes to genetic stability of native and T315I-mutated BCR-ABL expressing leukemic cells.

Author information

1
CHU de Poitiers, Service d'Oncologie Hématologique et Thérapie Cellulaire, Poitiers, France; INSERM U935, Poitiers, Université de Poitiers, France.
2
INSERM U935, Poitiers, Université de Poitiers, France; Hôpitaux Universitaires Paris Sud, Service de Cytogénétique Hôpital Antoine Beclere, France.
3
CHRU de Tours, Département d'Hématologie Biologique, Tours, France; CNRS UMR 7292 CICC, Equipe LNOx, Université de Tours, Tours, France.
4
INSERM U935, Human Embryonic Stem Cell Core Facility, Université Paris Sud 11, Villejuif, France; CEA, DSV-iMETI-SEPIA, BP6, 92265, Fontenay-aux-Roses Cedex, France.
5
INSERM U935, Poitiers, Université de Poitiers, France.
6
INSERM U935, Poitiers, Université de Poitiers, France; CHU de Poitiers, Service de Cancérologie Biologique, Poitiers, France.
7
INSERM U935, Human Embryonic Stem Cell Core Facility, Université Paris Sud 11, Villejuif, France; Hôpitaux Universitaires Paris Sud, Service de Cytogénétique Hôpital Antoine Beclere, France.
8
CHU de Poitiers, Service d'Oncologie Hématologique et Thérapie Cellulaire, Poitiers, France; INSERM CIC 1402, Université de Poitiers, Poitiers, France.
9
INSERM CIC 1402, Université de Poitiers, Poitiers, France.
10
INSERM U935, Poitiers, Université de Poitiers, France; INSERM U935 Université Paris Sud & Service d'Hématologie, Institur Federatif d'Hématologie IFHIPS, France. Electronic address: turviv33@gmail.com.

Abstract

Manganese Superoxide dismutase 2 (SOD2) plays a crucial role in antioxidant defense but there are no data suggesting its role in genetic instability in CML. We evaluated the effects of SOD2 silencing in human UT7 cell line expressing either non-mutated or T315I-mutated BCR-ABL. Array-CGH experiments detected in BCR-ABL-expressing cells silenced for SOD2 a major genetic instability within several chromosomal loci, especially in regions carrying the glypican family (duplicated) and β-defensin genes (deleted). In a large cohort of patients with chronic myeloid leukemia (CML), a significant decrease of SOD2 mRNA was observed. This reduction appeared inversely correlated with leukocytosis and Sokal score, high-risk patients showing lower SOD2 levels. The analysis of anti-oxidant gene expression analysis revealed a specific down-regulation of the expression of PRDX2 in UT7-BCR-ABL and UT7-T315I cells silenced for SOD2 expression. Gene set enrichment analysis performed between the two SOD2-dependent classes of CML patients revealed a significant enrichment of Reactive Oxygen Species (ROS) Pathway. Our data provide the first evidence for a link between SOD2 expression and genetic instability in CML. Consequently, SOD2 mRNA levels should be analyzed in prospective studies as patients with low SOD2 expression could be more prone to develop a mutator phenotype under TKI therapies.

KEYWORDS:

CML; Genetic instability; SOD2; Silencing

PMID:
29550484
DOI:
10.1016/j.bbrc.2018.03.023
[Indexed for MEDLINE]

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