EHA Library - The official digital education library of European Hematology Association (EHA)

ALTERED SETMAR EXPRESSION ASSOCIATES WITH CLINICAL CHARACTERISTICSIN CHRONIC LYMPHOCYTIC LEUKEMIA.
Author(s): ,
Flavia Piazera
Affiliations:
Laboratory of Molecular Patology of Cancer,University of Brasilia,Brasilia,Brazil
,
Roberto Lucena-Araujo
Affiliations:
Department of Internal Medicine,University of São Paulo,Ribeirão Preto,Brazil
,
Fabio Morato de Oliveira
Affiliations:
Department of Internal Medicine,University of São Paulo,Ribeirão Preto,Brazil
,
Eduardo Magalhaes Rego
Affiliations:
Department of Internal Medicine,University of São Paulo,Ribeirão Preto,Brazil
,
Felipe Saldanha-Araujo
Affiliations:
Department of Internal Medicine,University of São Paulo,Ribeirão Preto,Brazil
Fabio Pittela Silva
Affiliations:
Laboratory of Molecular Patology of Cancer,University of Brasilia,Brasilia,Brazil
(Abstract release date: 05/19/16) EHA Library. Piazera F. 06/09/16; 134681; PB1781
Prof. Flavia Piazera
Prof. Flavia Piazera
Contributions
Abstract
Abstract: PB1781

Type: Publication Only

Background
The Chronic lymphocytic leukemia (CLL) is the most common chronic lymphoid malignancy in the western population. To date, several studies have been developed to elucidate the genetic factors involved in the biology and progression of CLL. Epigenetic changes have been shown to be increasingly important in the genesis of various tumors and especially in chronic lymphoid neoplasms.Histone methylation is one of the leading and most studied epigenetic events. The gene SETMAR(or METNASE) was associated with carcinogenesis of acute myeloid leukemia by losing disjuntion checkpoint in cells treated with inhibitors of protein topo II alpha such as etoposide, doxorubicin and mitoxantrone. However, the role of SETMAR in CLL leukemogenesis remains unknown.

Aims
Determine relative expression of the gene in SETMAR CLL samples.

Methods
In this study, we evaluated the relative expression of SETMAR[FP1]  between a group of 59 CLL patients and 10 samples from peripheral blood of healthy blood donors by real-time qPCR.Quantification of SETMAR was performed by Real Time PCR (qPCR) and normalized to endogenous ACTIN expression. Results were analyzed by the comparative 2 -ΔΔCt method. The amount of target gene, normalized to the endogenous control gene and relative to a reference sample, was converted into relative quantification. Based on the distribution of SETMAR expression in CLL samples, we adopted the median value as the cutoff to dichotomize CLL patients in “low expression group (LEG)” and “high expression group (HEG)”. The expression of SETMAR was thencorrelated with clinical relevant prognostic factors such ascytogenetic, immunophenotypic and hematologic features in this disease.

Results
We found that SETMAR was significantly overexpressed in patients with CLL compared to controls (p <0.0014). After the dichotomy, the LEG showed high leukocyte count (p <0.0050), low platelet count (p <0.0489) and predominance of cytogenetic abnormalities (p <0.030). The clinical staging of BINET and expression of ZAP-70 did not show statistical significance between the LEG and the HEG. Our results shows that SETMAR expression is altered in CLL patients when compared to healthy controls, and revealed that a lower expression of SETMAR in patients is clinically associated with chromosomal instability and progression of the tumor mass though increased leukocytosis.

Conclusion
These findings are immediate in CLL samples, and further studies are necessary for evaluation as a prognostic factor in this disease.

Session topic: E-poster

Keyword(s): Chronic lymphocytic leukemia, Epigenetic
Abstract: PB1781

Type: Publication Only

Background
The Chronic lymphocytic leukemia (CLL) is the most common chronic lymphoid malignancy in the western population. To date, several studies have been developed to elucidate the genetic factors involved in the biology and progression of CLL. Epigenetic changes have been shown to be increasingly important in the genesis of various tumors and especially in chronic lymphoid neoplasms.Histone methylation is one of the leading and most studied epigenetic events. The gene SETMAR(or METNASE) was associated with carcinogenesis of acute myeloid leukemia by losing disjuntion checkpoint in cells treated with inhibitors of protein topo II alpha such as etoposide, doxorubicin and mitoxantrone. However, the role of SETMAR in CLL leukemogenesis remains unknown.

Aims
Determine relative expression of the gene in SETMAR CLL samples.

Methods
In this study, we evaluated the relative expression of SETMAR[FP1]  between a group of 59 CLL patients and 10 samples from peripheral blood of healthy blood donors by real-time qPCR.Quantification of SETMAR was performed by Real Time PCR (qPCR) and normalized to endogenous ACTIN expression. Results were analyzed by the comparative 2 -ΔΔCt method. The amount of target gene, normalized to the endogenous control gene and relative to a reference sample, was converted into relative quantification. Based on the distribution of SETMAR expression in CLL samples, we adopted the median value as the cutoff to dichotomize CLL patients in “low expression group (LEG)” and “high expression group (HEG)”. The expression of SETMAR was thencorrelated with clinical relevant prognostic factors such ascytogenetic, immunophenotypic and hematologic features in this disease.

Results
We found that SETMAR was significantly overexpressed in patients with CLL compared to controls (p <0.0014). After the dichotomy, the LEG showed high leukocyte count (p <0.0050), low platelet count (p <0.0489) and predominance of cytogenetic abnormalities (p <0.030). The clinical staging of BINET and expression of ZAP-70 did not show statistical significance between the LEG and the HEG. Our results shows that SETMAR expression is altered in CLL patients when compared to healthy controls, and revealed that a lower expression of SETMAR in patients is clinically associated with chromosomal instability and progression of the tumor mass though increased leukocytosis.

Conclusion
These findings are immediate in CLL samples, and further studies are necessary for evaluation as a prognostic factor in this disease.

Session topic: E-poster

Keyword(s): Chronic lymphocytic leukemia, Epigenetic

By clicking “Accept Terms & all Cookies” or by continuing to browse, you agree to the storing of third-party cookies on your device to enhance your user experience and agree to the user terms and conditions of this learning management system (LMS).

Cookie Settings
Accept Terms & all Cookies