TAZ GENE FROM HIPPO PATHWAY IS OVEREXPRESSED IN POLYCYTHEMIA VERA AND ESSENTIAL THROMBOCYTHEMIA PATIENTS
(Abstract release date: 05/21/15)
EHA Library. Cacemiro M. 06/12/15; 102907; PB1900
Maira Cacemiro
Contributions
Contributions
Abstract
Abstract: PB1900
Type: Publication Only
Background
Polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibosis (MF) are myeloproliferative neoplasms (MPN) characterized by the increase of mature hematopoietic cells of one or more of the myeloid series proliferation. MPN may present theJAK2V617F mutation which occurs in 95 % of PV patients and 50% of ET and MF patients. The JAK2V617F mutation constitutively active STAT3 transducer protein, which is related to apoptosis resistance and myeloproliferation in MNP. Although all the molecular knowlegde about MNP pathogenesis, these diseases do not have an efficient therapy. Thus, more studies related to MPN pathophysiology and description of new therapeutic targets, such as the molecules from Hippo pathway are relevant. The Hippo signaling pathway has been defined as a tumor suppressor pathway responsible for regulating the proliferation, differentiation and cell death. This pathway is composed of MST1/2, WW45, Lats1/2, Mob1 and YAP/TAZ proteins present in mammals.
Aims
To compare the TAZ gene expression among PV, ET, MF patients and controls (CTRL) subjects.
Methods
The leukocytes were obtained from peripheral blood of 23 PV patients (median age = 60 years; 13 men and 10 women), 21 ET patients (median age = 62 years; 10 men and 11 women), 21 MF patients (median age = 64 years; 16 men and 5 women) and 23 CTRL (median age = 58 years; 6 men and 17 women). The leukocytes were separated by Voluven gradient method. The RNA were extracted by Trizol® method and the cDNA were synthesized using High Capacity cDNA reverse transcription kit®. The gene expression was assessed by a real time PCR and the results were expressed as relative units of expression (RUE).
Results
Moreover, in PV patients the TAZ expression is higher in those JAK2V617F-negative patients.
Summary
The results indicate that TAZ gene may contribute to PV and ET pathogenesis since TAZ is well known for their regulation by the Hippo pathway acting as a transcriptional co?activator inducing expression of cell-proliferative and anti-apoptotic genes via interactions with specific transcription factors.
Keyword(s): Myeloproliferative disorder
Session topic: Publication Only
Type: Publication Only
Background
Polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibosis (MF) are myeloproliferative neoplasms (MPN) characterized by the increase of mature hematopoietic cells of one or more of the myeloid series proliferation. MPN may present theJAK2V617F mutation which occurs in 95 % of PV patients and 50% of ET and MF patients. The JAK2V617F mutation constitutively active STAT3 transducer protein, which is related to apoptosis resistance and myeloproliferation in MNP. Although all the molecular knowlegde about MNP pathogenesis, these diseases do not have an efficient therapy. Thus, more studies related to MPN pathophysiology and description of new therapeutic targets, such as the molecules from Hippo pathway are relevant. The Hippo signaling pathway has been defined as a tumor suppressor pathway responsible for regulating the proliferation, differentiation and cell death. This pathway is composed of MST1/2, WW45, Lats1/2, Mob1 and YAP/TAZ proteins present in mammals.
Aims
To compare the TAZ gene expression among PV, ET, MF patients and controls (CTRL) subjects.
Methods
The leukocytes were obtained from peripheral blood of 23 PV patients (median age = 60 years; 13 men and 10 women), 21 ET patients (median age = 62 years; 10 men and 11 women), 21 MF patients (median age = 64 years; 16 men and 5 women) and 23 CTRL (median age = 58 years; 6 men and 17 women). The leukocytes were separated by Voluven gradient method. The RNA were extracted by Trizol® method and the cDNA were synthesized using High Capacity cDNA reverse transcription kit®. The gene expression was assessed by a real time PCR and the results were expressed as relative units of expression (RUE).
Results
Moreover, in PV patients the TAZ expression is higher in those JAK2V617F-negative patients.
Summary
The results indicate that TAZ gene may contribute to PV and ET pathogenesis since TAZ is well known for their regulation by the Hippo pathway acting as a transcriptional co?activator inducing expression of cell-proliferative and anti-apoptotic genes via interactions with specific transcription factors.
Supported by FAPESP process 2014/04234-9
Keyword(s): Myeloproliferative disorder
Session topic: Publication Only
Abstract: PB1900
Type: Publication Only
Background
Polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibosis (MF) are myeloproliferative neoplasms (MPN) characterized by the increase of mature hematopoietic cells of one or more of the myeloid series proliferation. MPN may present theJAK2V617F mutation which occurs in 95 % of PV patients and 50% of ET and MF patients. The JAK2V617F mutation constitutively active STAT3 transducer protein, which is related to apoptosis resistance and myeloproliferation in MNP. Although all the molecular knowlegde about MNP pathogenesis, these diseases do not have an efficient therapy. Thus, more studies related to MPN pathophysiology and description of new therapeutic targets, such as the molecules from Hippo pathway are relevant. The Hippo signaling pathway has been defined as a tumor suppressor pathway responsible for regulating the proliferation, differentiation and cell death. This pathway is composed of MST1/2, WW45, Lats1/2, Mob1 and YAP/TAZ proteins present in mammals.
Aims
To compare the TAZ gene expression among PV, ET, MF patients and controls (CTRL) subjects.
Methods
The leukocytes were obtained from peripheral blood of 23 PV patients (median age = 60 years; 13 men and 10 women), 21 ET patients (median age = 62 years; 10 men and 11 women), 21 MF patients (median age = 64 years; 16 men and 5 women) and 23 CTRL (median age = 58 years; 6 men and 17 women). The leukocytes were separated by Voluven gradient method. The RNA were extracted by Trizol® method and the cDNA were synthesized using High Capacity cDNA reverse transcription kit®. The gene expression was assessed by a real time PCR and the results were expressed as relative units of expression (RUE).
Results
Moreover, in PV patients the TAZ expression is higher in those JAK2V617F-negative patients.
Summary
The results indicate that TAZ gene may contribute to PV and ET pathogenesis since TAZ is well known for their regulation by the Hippo pathway acting as a transcriptional co?activator inducing expression of cell-proliferative and anti-apoptotic genes via interactions with specific transcription factors.
Keyword(s): Myeloproliferative disorder
Session topic: Publication Only
Type: Publication Only
Background
Polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibosis (MF) are myeloproliferative neoplasms (MPN) characterized by the increase of mature hematopoietic cells of one or more of the myeloid series proliferation. MPN may present theJAK2V617F mutation which occurs in 95 % of PV patients and 50% of ET and MF patients. The JAK2V617F mutation constitutively active STAT3 transducer protein, which is related to apoptosis resistance and myeloproliferation in MNP. Although all the molecular knowlegde about MNP pathogenesis, these diseases do not have an efficient therapy. Thus, more studies related to MPN pathophysiology and description of new therapeutic targets, such as the molecules from Hippo pathway are relevant. The Hippo signaling pathway has been defined as a tumor suppressor pathway responsible for regulating the proliferation, differentiation and cell death. This pathway is composed of MST1/2, WW45, Lats1/2, Mob1 and YAP/TAZ proteins present in mammals.
Aims
To compare the TAZ gene expression among PV, ET, MF patients and controls (CTRL) subjects.
Methods
The leukocytes were obtained from peripheral blood of 23 PV patients (median age = 60 years; 13 men and 10 women), 21 ET patients (median age = 62 years; 10 men and 11 women), 21 MF patients (median age = 64 years; 16 men and 5 women) and 23 CTRL (median age = 58 years; 6 men and 17 women). The leukocytes were separated by Voluven gradient method. The RNA were extracted by Trizol® method and the cDNA were synthesized using High Capacity cDNA reverse transcription kit®. The gene expression was assessed by a real time PCR and the results were expressed as relative units of expression (RUE).
Results
Moreover, in PV patients the TAZ expression is higher in those JAK2V617F-negative patients.
Summary
The results indicate that TAZ gene may contribute to PV and ET pathogenesis since TAZ is well known for their regulation by the Hippo pathway acting as a transcriptional co?activator inducing expression of cell-proliferative and anti-apoptotic genes via interactions with specific transcription factors.
Supported by FAPESP process 2014/04234-9
Keyword(s): Myeloproliferative disorder
Session topic: Publication Only
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