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EVALUATION OF EXPRESSION OF MIRNAS ISOLATED MICROVESICLES OF PATIENTS WITH MYELOFIBROSIS ASSOCIATED WITH DISEASE
Author(s):
Leane Rodrigues
,
Leane Rodrigues
Affiliations:
BIOTECNOLOGIA,UNIVERSIDADE CATÓLICA DE BRASÍLIA,BRASÍLIA,Brazil
Jordan Barros
,
Jordan Barros
Affiliations:
BIOTECNOLOGIA,UNIVERSIDADE CATÓLICA DE BRASÍLIA,BRASÍLIA,Brazil
Alexandre Nonino
,
Alexandre Nonino
Affiliations:
BIOTECNOLOGIA,UNIVERSIDADE CATÓLICA DE BRASÍLIA,BRASÍLIA,Brazil
Cintia Mascarenhas
Cintia Mascarenhas
Affiliations:
BIOTECNOLOGIA,UNIVERSIDADE CATÓLICA DE BRASÍLIA,BRASÍLIA,Brazil
(Abstract release date: 05/18/17) EHA Library. Mascarenhas C. 05/18/17; 182739; PB2025
Cintia Mascarenhas
Cintia Mascarenhas
Contributions
PDF Abstract
Abstract

Abstract: PB2025

Type: Publication Only

Background

Myelofibrosis is a hematological disease inserted in the group of myeloproliferative neoplasias. It has as main characteristic fibrosis of the bone marrow, consequence of a variety of histological changes presented in the medullary microenvironment. The development of the disease is related to the clonal expansion of myeloid stem cells, abnormal expression of cytokines, hypercellularity of myeloid lines and also extramedullary hematopoiesis. The pathophysiology of myelofibrosis involves the activation of signal transduction pathways, which may occur due to genetic rearrangements and mutations that alter the structure of protein tyrosine kinases, making hematopoietic progenitor cells independent or hypersensitive to cytokines, generating anomalous cellular behavior.
Myelofibrosis is a hematological disease inserted in the group of myeloproliferative neoplasias. It has as main characteristic fibrosis of the bone marrow, consequence of a variety of histological changes presented in the medullary microenvironment. The development of the disease is related to the clonal expansion of myeloid stem cells, abnormal expression of cytokines, hypercellularity of myeloid lines and also extramedullary hematopoiesis. The pathophysiology of myelofibrosis involves the activation of signal transduction pathways, which may occur due to genetic rearrangements and mutations that alter the structure of protein tyrosine kinases, making hematopoietic progenitor cells independent or hypersensitive to cytokines, generating anomalous cellular behavior.

Aims
Recent studies have shown that microvesicles produced by cells of the organism may be associated with the cellular communication process due to their intravesicular content and that miRNAs also found in this content are able to regulate diverse cellular processes. The expression of some microRNAs is associated with hematopoietic processes such as the transformation of myeloid, erythroid and megakaryocytic progenitors. These can regulate the hematopoiesis of normal stem cells and also of compromised progenitors, having an important role in the pathogenesis of some acquired hematological malignancies. The objective of this work is to investigate the presence of specific miRNAs in microvesicles excreted in peripheral blood plasma of patients with myelofibrosis, which may be related to cellular communication.

Methods
Microvesicles were isolated from the plasma by ultracentrifugation method and through molecular biology techniques it was possible to validate their presence. Assays by qPCR were performed to evaluate the presence of specific miRNAs.

Results

We used the miRNAs described in the literature as influential in the process of hematological disorders. They are: mir146b, mir 150, mir 29a and 155.
After analysis of miRNA differential expression, miR-29a and miR-155 were less expressed in MF patients compared to healthy donors (P <0.02 and P <0.03), and miR-223 did not Presented a statistically significant difference. Data on miR-29a corroborate in part with the literature, since the data presented here relate to miRNA carried by VEs rather than serum / plasma. However, low levels of miR-29a expression are related to aberrant auto-renewal of hematopoietic progenitor cells, thus indicating that VEs may contribute to this mechanism. As for miR-155, the data obtained do not corroborate with the literature and, possibly, the VEs do not participate in the mechanism of regulation of Megacariopoiese by miR-155
We used the miRNAs described in the literature as influential in the process of hematological disorders. They are: mir146b, mir 150, mir 29a and 155.After analysis of miRNA differential expression, miR-29a and miR-155 were less expressed in MF patients compared to healthy donors (P <0.02 and P <0.03), and miR-223 did not Presented a statistically significant difference. Data on miR-29a corroborate in part with the literature, since the data presented here relate to miRNA carried by VEs rather than serum / plasma. However, low levels of miR-29a expression are related to aberrant auto-renewal of hematopoietic progenitor cells, thus indicating that VEs may contribute to this mechanism. As for miR-155, the data obtained do not corroborate with the literature and, possibly, the VEs do not participate in the mechanism of regulation of Megacariopoiese by miR-155.

Conclusion
MiRNAs present in the microvesic content may collaborate in the cellular communication process in myeloproliferative diseases and induce hematopoietic disorders.

Session topic: 15. Myeloproliferative neoplasms - Biology

Keyword(s): Myelofibrosis, Microvesicles, Myeloproliferative disorder

Abstract: PB2025

Type: Publication Only

Background

Myelofibrosis is a hematological disease inserted in the group of myeloproliferative neoplasias. It has as main characteristic fibrosis of the bone marrow, consequence of a variety of histological changes presented in the medullary microenvironment. The development of the disease is related to the clonal expansion of myeloid stem cells, abnormal expression of cytokines, hypercellularity of myeloid lines and also extramedullary hematopoiesis. The pathophysiology of myelofibrosis involves the activation of signal transduction pathways, which may occur due to genetic rearrangements and mutations that alter the structure of protein tyrosine kinases, making hematopoietic progenitor cells independent or hypersensitive to cytokines, generating anomalous cellular behavior.
Myelofibrosis is a hematological disease inserted in the group of myeloproliferative neoplasias. It has as main characteristic fibrosis of the bone marrow, consequence of a variety of histological changes presented in the medullary microenvironment. The development of the disease is related to the clonal expansion of myeloid stem cells, abnormal expression of cytokines, hypercellularity of myeloid lines and also extramedullary hematopoiesis. The pathophysiology of myelofibrosis involves the activation of signal transduction pathways, which may occur due to genetic rearrangements and mutations that alter the structure of protein tyrosine kinases, making hematopoietic progenitor cells independent or hypersensitive to cytokines, generating anomalous cellular behavior.

Aims
Recent studies have shown that microvesicles produced by cells of the organism may be associated with the cellular communication process due to their intravesicular content and that miRNAs also found in this content are able to regulate diverse cellular processes. The expression of some microRNAs is associated with hematopoietic processes such as the transformation of myeloid, erythroid and megakaryocytic progenitors. These can regulate the hematopoiesis of normal stem cells and also of compromised progenitors, having an important role in the pathogenesis of some acquired hematological malignancies. The objective of this work is to investigate the presence of specific miRNAs in microvesicles excreted in peripheral blood plasma of patients with myelofibrosis, which may be related to cellular communication.

Methods
Microvesicles were isolated from the plasma by ultracentrifugation method and through molecular biology techniques it was possible to validate their presence. Assays by qPCR were performed to evaluate the presence of specific miRNAs.

Results

We used the miRNAs described in the literature as influential in the process of hematological disorders. They are: mir146b, mir 150, mir 29a and 155.
After analysis of miRNA differential expression, miR-29a and miR-155 were less expressed in MF patients compared to healthy donors (P <0.02 and P <0.03), and miR-223 did not Presented a statistically significant difference. Data on miR-29a corroborate in part with the literature, since the data presented here relate to miRNA carried by VEs rather than serum / plasma. However, low levels of miR-29a expression are related to aberrant auto-renewal of hematopoietic progenitor cells, thus indicating that VEs may contribute to this mechanism. As for miR-155, the data obtained do not corroborate with the literature and, possibly, the VEs do not participate in the mechanism of regulation of Megacariopoiese by miR-155
We used the miRNAs described in the literature as influential in the process of hematological disorders. They are: mir146b, mir 150, mir 29a and 155.After analysis of miRNA differential expression, miR-29a and miR-155 were less expressed in MF patients compared to healthy donors (P <0.02 and P <0.03), and miR-223 did not Presented a statistically significant difference. Data on miR-29a corroborate in part with the literature, since the data presented here relate to miRNA carried by VEs rather than serum / plasma. However, low levels of miR-29a expression are related to aberrant auto-renewal of hematopoietic progenitor cells, thus indicating that VEs may contribute to this mechanism. As for miR-155, the data obtained do not corroborate with the literature and, possibly, the VEs do not participate in the mechanism of regulation of Megacariopoiese by miR-155.

Conclusion
MiRNAs present in the microvesic content may collaborate in the cellular communication process in myeloproliferative diseases and induce hematopoietic disorders.

Session topic: 15. Myeloproliferative neoplasms - Biology

Keyword(s): Myelofibrosis, Microvesicles, Myeloproliferative disorder

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