DIDO 2 LOW EXPRESSION IN CML IS LINKED TO APOPTOSIS RESISTANCE
(Abstract release date: 05/21/15)
EHA Library. Coelho M. 06/12/15; 102916; PB1732
Disclosure(s): USPUSP
Maria Coelho
Contributions
Contributions
Abstract
Abstract: PB1732
Type: Publication Only
Background
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm which patients are diagnosed by the BCR-ABL1 oncogene presence. BCR-ABL1 encodes Bcr-Abl, a tyrosine kinase protein responsible for CML pathogenesis and apoptosis impairment. CML patients are treated with tyrosine kinase inhibitors (TKI). However resistance to TKI have been described and can be associated with Bcr-Abl dependent and independent mechanisms. Therefore new therapeutic targets and CML pathogenesis, including the possible involvement of DIDO, should be investigated. DIDO is a gene that encodes transcription factors of apoptosis-inducing genes and has three different isoforms: DIDO 1, 2 and 3. In physiological conditions DIDO is present in small concentrations in cytoplasm, but during the process of apoptosis its protein expression rises and then it is translocated to the nucleus. Increased expression of DIDO is therefore associated with the induction of apoptosis process. In myeloproliferative diseases DIDO is defined as a tumor supressor gene. Expression changes of isoforms 2 and 3 were already described in the pathophysiology of myeloid neoplasms.
Aims
To evaluate the association between apoptosis resistance and Dido expression by the quantification of the expression of DIDO 1, 2 and 3 genes in CML patients in chronic and advanced phases and in healthy subjects.
Methods
39 CML patients (median age = 45 years; 19 women and 20 men) and 16 controls (median age = 35 years; 10 women and 6 men) were studied. Peripheral blood mononuclear cells were isolated by Ficoll-Hypaque density gradient method and the mRNA was extracted by Trizol® method. The cDNA was synthesized by High Capacity cDNA Reverse Trasnscription® Kit in conventional PCR and gene expression analysis of isoforms 1, 2 and 3 of DIDO gene was performed by real-time PCR (Applied Biosystems 7500 Real Time PCR®). The results were expressed as relative units of expression. The gene expression comparison of DIDO1, 2 and 3 between health subjects and patients in different stages of the disease was assessed by Mann-Whitney statistical test.
Results
The DIDO 2 expression was lower in advanced stages (median = 1.352 and P = 0.0130) in comparison to controls (median = 4.886 and P = 0.0130). Comparison of isoforms 1 and 3 expression between CML patients and controls yielded no significant differences.
Summary
The results indicate that DIDO 2 low expression may be linked to apoptosis resistance in CML patients. In addition the results also suggest a different role for each of the three different gene isoforms in CML.
Keyword(s): Apoptosis, Chronic myeloid leukemia
Session topic: Publication Only
Type: Publication Only
Background
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm which patients are diagnosed by the BCR-ABL1 oncogene presence. BCR-ABL1 encodes Bcr-Abl, a tyrosine kinase protein responsible for CML pathogenesis and apoptosis impairment. CML patients are treated with tyrosine kinase inhibitors (TKI). However resistance to TKI have been described and can be associated with Bcr-Abl dependent and independent mechanisms. Therefore new therapeutic targets and CML pathogenesis, including the possible involvement of DIDO, should be investigated. DIDO is a gene that encodes transcription factors of apoptosis-inducing genes and has three different isoforms: DIDO 1, 2 and 3. In physiological conditions DIDO is present in small concentrations in cytoplasm, but during the process of apoptosis its protein expression rises and then it is translocated to the nucleus. Increased expression of DIDO is therefore associated with the induction of apoptosis process. In myeloproliferative diseases DIDO is defined as a tumor supressor gene. Expression changes of isoforms 2 and 3 were already described in the pathophysiology of myeloid neoplasms.
Aims
To evaluate the association between apoptosis resistance and Dido expression by the quantification of the expression of DIDO 1, 2 and 3 genes in CML patients in chronic and advanced phases and in healthy subjects.
Methods
39 CML patients (median age = 45 years; 19 women and 20 men) and 16 controls (median age = 35 years; 10 women and 6 men) were studied. Peripheral blood mononuclear cells were isolated by Ficoll-Hypaque density gradient method and the mRNA was extracted by Trizol® method. The cDNA was synthesized by High Capacity cDNA Reverse Trasnscription® Kit in conventional PCR and gene expression analysis of isoforms 1, 2 and 3 of DIDO gene was performed by real-time PCR (Applied Biosystems 7500 Real Time PCR®). The results were expressed as relative units of expression. The gene expression comparison of DIDO1, 2 and 3 between health subjects and patients in different stages of the disease was assessed by Mann-Whitney statistical test.
Results
The DIDO 2 expression was lower in advanced stages (median = 1.352 and P = 0.0130) in comparison to controls (median = 4.886 and P = 0.0130). Comparison of isoforms 1 and 3 expression between CML patients and controls yielded no significant differences.
Summary
The results indicate that DIDO 2 low expression may be linked to apoptosis resistance in CML patients. In addition the results also suggest a different role for each of the three different gene isoforms in CML.
Keyword(s): Apoptosis, Chronic myeloid leukemia
Session topic: Publication Only
Abstract: PB1732
Type: Publication Only
Background
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm which patients are diagnosed by the BCR-ABL1 oncogene presence. BCR-ABL1 encodes Bcr-Abl, a tyrosine kinase protein responsible for CML pathogenesis and apoptosis impairment. CML patients are treated with tyrosine kinase inhibitors (TKI). However resistance to TKI have been described and can be associated with Bcr-Abl dependent and independent mechanisms. Therefore new therapeutic targets and CML pathogenesis, including the possible involvement of DIDO, should be investigated. DIDO is a gene that encodes transcription factors of apoptosis-inducing genes and has three different isoforms: DIDO 1, 2 and 3. In physiological conditions DIDO is present in small concentrations in cytoplasm, but during the process of apoptosis its protein expression rises and then it is translocated to the nucleus. Increased expression of DIDO is therefore associated with the induction of apoptosis process. In myeloproliferative diseases DIDO is defined as a tumor supressor gene. Expression changes of isoforms 2 and 3 were already described in the pathophysiology of myeloid neoplasms.
Aims
To evaluate the association between apoptosis resistance and Dido expression by the quantification of the expression of DIDO 1, 2 and 3 genes in CML patients in chronic and advanced phases and in healthy subjects.
Methods
39 CML patients (median age = 45 years; 19 women and 20 men) and 16 controls (median age = 35 years; 10 women and 6 men) were studied. Peripheral blood mononuclear cells were isolated by Ficoll-Hypaque density gradient method and the mRNA was extracted by Trizol® method. The cDNA was synthesized by High Capacity cDNA Reverse Trasnscription® Kit in conventional PCR and gene expression analysis of isoforms 1, 2 and 3 of DIDO gene was performed by real-time PCR (Applied Biosystems 7500 Real Time PCR®). The results were expressed as relative units of expression. The gene expression comparison of DIDO1, 2 and 3 between health subjects and patients in different stages of the disease was assessed by Mann-Whitney statistical test.
Results
The DIDO 2 expression was lower in advanced stages (median = 1.352 and P = 0.0130) in comparison to controls (median = 4.886 and P = 0.0130). Comparison of isoforms 1 and 3 expression between CML patients and controls yielded no significant differences.
Summary
The results indicate that DIDO 2 low expression may be linked to apoptosis resistance in CML patients. In addition the results also suggest a different role for each of the three different gene isoforms in CML.
Keyword(s): Apoptosis, Chronic myeloid leukemia
Session topic: Publication Only
Type: Publication Only
Background
Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm which patients are diagnosed by the BCR-ABL1 oncogene presence. BCR-ABL1 encodes Bcr-Abl, a tyrosine kinase protein responsible for CML pathogenesis and apoptosis impairment. CML patients are treated with tyrosine kinase inhibitors (TKI). However resistance to TKI have been described and can be associated with Bcr-Abl dependent and independent mechanisms. Therefore new therapeutic targets and CML pathogenesis, including the possible involvement of DIDO, should be investigated. DIDO is a gene that encodes transcription factors of apoptosis-inducing genes and has three different isoforms: DIDO 1, 2 and 3. In physiological conditions DIDO is present in small concentrations in cytoplasm, but during the process of apoptosis its protein expression rises and then it is translocated to the nucleus. Increased expression of DIDO is therefore associated with the induction of apoptosis process. In myeloproliferative diseases DIDO is defined as a tumor supressor gene. Expression changes of isoforms 2 and 3 were already described in the pathophysiology of myeloid neoplasms.
Aims
To evaluate the association between apoptosis resistance and Dido expression by the quantification of the expression of DIDO 1, 2 and 3 genes in CML patients in chronic and advanced phases and in healthy subjects.
Methods
39 CML patients (median age = 45 years; 19 women and 20 men) and 16 controls (median age = 35 years; 10 women and 6 men) were studied. Peripheral blood mononuclear cells were isolated by Ficoll-Hypaque density gradient method and the mRNA was extracted by Trizol® method. The cDNA was synthesized by High Capacity cDNA Reverse Trasnscription® Kit in conventional PCR and gene expression analysis of isoforms 1, 2 and 3 of DIDO gene was performed by real-time PCR (Applied Biosystems 7500 Real Time PCR®). The results were expressed as relative units of expression. The gene expression comparison of DIDO1, 2 and 3 between health subjects and patients in different stages of the disease was assessed by Mann-Whitney statistical test.
Results
The DIDO 2 expression was lower in advanced stages (median = 1.352 and P = 0.0130) in comparison to controls (median = 4.886 and P = 0.0130). Comparison of isoforms 1 and 3 expression between CML patients and controls yielded no significant differences.
Summary
The results indicate that DIDO 2 low expression may be linked to apoptosis resistance in CML patients. In addition the results also suggest a different role for each of the three different gene isoforms in CML.
Keyword(s): Apoptosis, Chronic myeloid leukemia
Session topic: Publication Only
{{ help_message }}
{{filter}}