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

LONG NON-CODING RNAS IN MULTIPLE MYELOMA
Author(s): ,
Lenka Sedlaříková
Affiliations:
Babak Myeloma Group, Department of Pathological Physiology, Faculty of Medicine,Masaryk University,Brno,Czech Republic
,
Barbora Gromesová
Affiliations:
Babak Myeloma Group, Department of Pathological Physiology, Faculty of Medicine,Masaryk University,Brno,Czech Republic
,
Veronika Kubaczková
Affiliations:
Babak Myeloma Group, Department of Pathological Physiology, Faculty of Medicine,Masaryk University,Brno,Czech Republic
,
Lenka Radová
Affiliations:
Central European Institute of Technology,Masaryk University,Brno,Czech Republic
,
Martina Almáši
Affiliations:
Department of Clinical Hematology,University Hospital Brno,Brno,Czech Republic
,
Miroslav Penka
Affiliations:
Department of Clinical Hematology,University Hospital Brno,Brno,Czech Republic
,
Zdeněk Adam
Affiliations:
Department of Internal Medicine - Hematooncology,University Hospital Brno,Brno,Czech Republic
,
Luděk Pour
Affiliations:
Department of Internal Medicine - Hematooncology,University Hospital Brno,Brno,Czech Republic
,
Marta Krejčí
Affiliations:
Department of Internal Medicine - Hematooncology,University Hospital Brno,Brno,Czech Republic
,
Sabina Ševčíková
Affiliations:
Babak Myeloma Group, Department of Pathological Physiology, Faculty of Medicine,Masaryk University,Brno,Czech Republic;Department of Clinical Hematology,University Hospital Brno,Brno,Czech Republic
Roman Hájek
Affiliations:
Babak Myeloma Group, Department of Pathological Physiology, Faculty of Medicine,Masaryk University,Brno,Czech Republic;Department of Clinical Hematology,University Hospital Brno,Brno,Czech Republic;Department of Hematooncology,University Hospital Ostrava,
(Abstract release date: 05/19/16) EHA Library. Kubaczková V. 06/09/16; 132805; E1256
Dr. Veronika Kubaczková
Dr. Veronika Kubaczková
Contributions
Abstract
Abstract: E1256

Type: Eposter Presentation

Background
Multiple myeloma (MM) is the second most common hematological malignancy in the world. It is characterized by increasing rate of various genetic mutations and dysregulated pathways. This work aims to find out if this observed dysregulation may be partly caused by a subgroup of non-coding RNAs, the so-called long non-coding RNA molecules (lncRNA). These molecules are over 200 nt long, primarily localized in the nucleus, and it seems increasingly obvious that lncRNAs play a crucial role in human diseases including cancer.

Aims
The goal of this study was to identify a disease-specific cellular lncRNA signature using a cohort of MM patients in comparison to healthy donors.

Methods
Fifty CD138+ samples obtained from newly diagnosed MM patients and healthy donors (HD) were evaluated for this study. Screening analysis of 83 lncRNA was performed on 6 MM patients and 6 HD using RT2 lncRNA PCR Array – Human lncRNA Finder (Qiagen). Significantly deregulated lncRNAs between MM vs HD were validated by qPCR using relative quantification approach 2-ΔCt on a larger cohort of patients and HD. Receiver Operating Characteristic (ROC) analysis was used to calculate specificity and sensitivity of each lncRNA. P values <0.05 were considered significant.

Results
RT2 lncRNA PCR Array profiling revealed 27 deregulated lncRNAs (all p<0.01) between MM patients and HD. ZFAS1, UCA1, BDNF-AS, NEAT1 and FAS-AS1 expression levels were further verified on a bigger cohort of MM and HD samples. UCA1 was significantly down-regulated (p<0.0001), NEAT1 and BDNF-AS were up-regulated in MM samples when compared with HD (both p<0.00000001). To discriminate MM from HD, receiver operating characteristic (ROC) curve was calculated. It revealed sensitivity of 100% and specificity of 100%, and area under curve (AUC) = 1.000 for NEAT1 and BDNF-AS lncRNA expression and sensitivity of 95.24% and specificity of 75%, and area under curve (AUC) = 0.905 for UCA1 expression levels. We suppose that these dysregulated lncRNAs could have a biological relevance in MM since BDNF-AS is an antisense RNA for BDNF, a significant stimulating factor of osteoclasts in MM, NEAT1 and UCA1 were described as dysregulated in several types of cancer, including hematological malignancies.

Conclusion
Altogether, our first observations demonstrate that cellular lncRNA UCA1, NEAT1 and BDNF-AS may be involved in pathophysiological processes occurring in MM cells and prompt further studies in this field.Grant support: AZV 15-29508A

Session topic: E-poster

Keyword(s): Multiple myeloma
Abstract: E1256

Type: Eposter Presentation

Background
Multiple myeloma (MM) is the second most common hematological malignancy in the world. It is characterized by increasing rate of various genetic mutations and dysregulated pathways. This work aims to find out if this observed dysregulation may be partly caused by a subgroup of non-coding RNAs, the so-called long non-coding RNA molecules (lncRNA). These molecules are over 200 nt long, primarily localized in the nucleus, and it seems increasingly obvious that lncRNAs play a crucial role in human diseases including cancer.

Aims
The goal of this study was to identify a disease-specific cellular lncRNA signature using a cohort of MM patients in comparison to healthy donors.

Methods
Fifty CD138+ samples obtained from newly diagnosed MM patients and healthy donors (HD) were evaluated for this study. Screening analysis of 83 lncRNA was performed on 6 MM patients and 6 HD using RT2 lncRNA PCR Array – Human lncRNA Finder (Qiagen). Significantly deregulated lncRNAs between MM vs HD were validated by qPCR using relative quantification approach 2-ΔCt on a larger cohort of patients and HD. Receiver Operating Characteristic (ROC) analysis was used to calculate specificity and sensitivity of each lncRNA. P values <0.05 were considered significant.

Results
RT2 lncRNA PCR Array profiling revealed 27 deregulated lncRNAs (all p<0.01) between MM patients and HD. ZFAS1, UCA1, BDNF-AS, NEAT1 and FAS-AS1 expression levels were further verified on a bigger cohort of MM and HD samples. UCA1 was significantly down-regulated (p<0.0001), NEAT1 and BDNF-AS were up-regulated in MM samples when compared with HD (both p<0.00000001). To discriminate MM from HD, receiver operating characteristic (ROC) curve was calculated. It revealed sensitivity of 100% and specificity of 100%, and area under curve (AUC) = 1.000 for NEAT1 and BDNF-AS lncRNA expression and sensitivity of 95.24% and specificity of 75%, and area under curve (AUC) = 0.905 for UCA1 expression levels. We suppose that these dysregulated lncRNAs could have a biological relevance in MM since BDNF-AS is an antisense RNA for BDNF, a significant stimulating factor of osteoclasts in MM, NEAT1 and UCA1 were described as dysregulated in several types of cancer, including hematological malignancies.

Conclusion
Altogether, our first observations demonstrate that cellular lncRNA UCA1, NEAT1 and BDNF-AS may be involved in pathophysiological processes occurring in MM cells and prompt further studies in this field.Grant support: AZV 15-29508A

Session topic: E-poster

Keyword(s): Multiple myeloma

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