ARE TP53BETA AND TP53GAMMA EXPRESSION LEVELS CORRELATED TO NPM1/FLT3 MUTATIONAL STATUS?
(Abstract release date: 05/19/16)
EHA Library. Matiakowska K. 06/09/16; 134548; PB1648
Ms. Karolina Matiakowska
Contributions
Contributions
Abstract
Abstract: PB1648
Type: Publication Only
Background
TP53 encodes a tumor suppressor protein which consists of transactivation, DNA-binding and oligomerization domains. Due to alternative splicing it may exist in 13 different isoforms. Alternative splicing of intron 9 leads to production of 2 different proteins, p53β and p53γ, without oligomerization domain (stop codon is localized in exon 9b). These isoforms can be present in acute myeloid leukemia (AML) cells. p53β binds to BAX promoter and can induce apoptosis independent from p53 wt. It also regulates p53 activity. In AML high expression of p53β and p53γ proteins may play role in response to treatment by enhancing cells sensitivity to chemotherapy. It has been showed that patients have longer survival after treatment. NPM1 (nucleophosmin gene) mutations are frequent alterations in normal karyotype AML (NK AML). Until now 56 different mutations of exon 12 of NPM1 have been described, mostly insertions. The NPM protein plays an important role in cell cycle and apoptosis control. It cooperates with several proteins, including p53 and ARF. While patients with NPM1 mutations are stratified to favorable risk group, internal tandem duplications (ITD) in the fms-like tyrosine kinase-3 gene (FLT3) (i.e. FLT3ITD) are poor prognosis factors.
Aims
The aim of the study was to assess mutational status of NPM1/FLT3 in association with TP53beta and TP53gamma expression levels.
Methods
56 NK AML patients with NPM1 and/or FLT3ITD mutations were included in the study. Analysis of TP53β and TP53γ expression levels was possible only in 36 patients. Relative expression results were analyzed with ΔΔCt method, with ABL as a control gene and K562 cell line as a calibrator.
Results
In all 36 cases, TP53β and TP53γ transcripts were detected. 17 patients were NPM1+/FLT3-, 14 were NPM1+/FLT3+ and 5 were NPM1-/FLT3+. Assessed median expression level of TP53β was much higher (ΔΔCt 43,87) than TP53γ (ΔΔCt 10,52; p=0,000027). Furthermore, according to statistical analysis, expression level of TP53γ was significantly associated with NPM1/FLT3 mutations (p=0,008). We also classified patients according to median expression value of TP53 to two groups: with overexpression or with small expression. Median WBC count in patients with overexpression of both isoforms was higher (75,4 G/L) than in group where expression of both isoforms was below median value (30G/L). Expression level of TP53γ was also correlated to WBC (p=0,05) and patients’ age (p=0,015).
Conclusion
Obtained results may indicate a clinical importance of analysis TP53 isoforms expression together with clinical data of patients.
Session topic: E-poster
Keyword(s): Acute myeloid leukemia, Expression, Flt3-ITD
Type: Publication Only
Background
TP53 encodes a tumor suppressor protein which consists of transactivation, DNA-binding and oligomerization domains. Due to alternative splicing it may exist in 13 different isoforms. Alternative splicing of intron 9 leads to production of 2 different proteins, p53β and p53γ, without oligomerization domain (stop codon is localized in exon 9b). These isoforms can be present in acute myeloid leukemia (AML) cells. p53β binds to BAX promoter and can induce apoptosis independent from p53 wt. It also regulates p53 activity. In AML high expression of p53β and p53γ proteins may play role in response to treatment by enhancing cells sensitivity to chemotherapy. It has been showed that patients have longer survival after treatment. NPM1 (nucleophosmin gene) mutations are frequent alterations in normal karyotype AML (NK AML). Until now 56 different mutations of exon 12 of NPM1 have been described, mostly insertions. The NPM protein plays an important role in cell cycle and apoptosis control. It cooperates with several proteins, including p53 and ARF. While patients with NPM1 mutations are stratified to favorable risk group, internal tandem duplications (ITD) in the fms-like tyrosine kinase-3 gene (FLT3) (i.e. FLT3ITD) are poor prognosis factors.
Aims
The aim of the study was to assess mutational status of NPM1/FLT3 in association with TP53beta and TP53gamma expression levels.
Methods
56 NK AML patients with NPM1 and/or FLT3ITD mutations were included in the study. Analysis of TP53β and TP53γ expression levels was possible only in 36 patients. Relative expression results were analyzed with ΔΔCt method, with ABL as a control gene and K562 cell line as a calibrator.
Results
In all 36 cases, TP53β and TP53γ transcripts were detected. 17 patients were NPM1+/FLT3-, 14 were NPM1+/FLT3+ and 5 were NPM1-/FLT3+. Assessed median expression level of TP53β was much higher (ΔΔCt 43,87) than TP53γ (ΔΔCt 10,52; p=0,000027). Furthermore, according to statistical analysis, expression level of TP53γ was significantly associated with NPM1/FLT3 mutations (p=0,008). We also classified patients according to median expression value of TP53 to two groups: with overexpression or with small expression. Median WBC count in patients with overexpression of both isoforms was higher (75,4 G/L) than in group where expression of both isoforms was below median value (30G/L). Expression level of TP53γ was also correlated to WBC (p=0,05) and patients’ age (p=0,015).
Conclusion
Obtained results may indicate a clinical importance of analysis TP53 isoforms expression together with clinical data of patients.
Session topic: E-poster
Keyword(s): Acute myeloid leukemia, Expression, Flt3-ITD
Abstract: PB1648
Type: Publication Only
Background
TP53 encodes a tumor suppressor protein which consists of transactivation, DNA-binding and oligomerization domains. Due to alternative splicing it may exist in 13 different isoforms. Alternative splicing of intron 9 leads to production of 2 different proteins, p53β and p53γ, without oligomerization domain (stop codon is localized in exon 9b). These isoforms can be present in acute myeloid leukemia (AML) cells. p53β binds to BAX promoter and can induce apoptosis independent from p53 wt. It also regulates p53 activity. In AML high expression of p53β and p53γ proteins may play role in response to treatment by enhancing cells sensitivity to chemotherapy. It has been showed that patients have longer survival after treatment. NPM1 (nucleophosmin gene) mutations are frequent alterations in normal karyotype AML (NK AML). Until now 56 different mutations of exon 12 of NPM1 have been described, mostly insertions. The NPM protein plays an important role in cell cycle and apoptosis control. It cooperates with several proteins, including p53 and ARF. While patients with NPM1 mutations are stratified to favorable risk group, internal tandem duplications (ITD) in the fms-like tyrosine kinase-3 gene (FLT3) (i.e. FLT3ITD) are poor prognosis factors.
Aims
The aim of the study was to assess mutational status of NPM1/FLT3 in association with TP53beta and TP53gamma expression levels.
Methods
56 NK AML patients with NPM1 and/or FLT3ITD mutations were included in the study. Analysis of TP53β and TP53γ expression levels was possible only in 36 patients. Relative expression results were analyzed with ΔΔCt method, with ABL as a control gene and K562 cell line as a calibrator.
Results
In all 36 cases, TP53β and TP53γ transcripts were detected. 17 patients were NPM1+/FLT3-, 14 were NPM1+/FLT3+ and 5 were NPM1-/FLT3+. Assessed median expression level of TP53β was much higher (ΔΔCt 43,87) than TP53γ (ΔΔCt 10,52; p=0,000027). Furthermore, according to statistical analysis, expression level of TP53γ was significantly associated with NPM1/FLT3 mutations (p=0,008). We also classified patients according to median expression value of TP53 to two groups: with overexpression or with small expression. Median WBC count in patients with overexpression of both isoforms was higher (75,4 G/L) than in group where expression of both isoforms was below median value (30G/L). Expression level of TP53γ was also correlated to WBC (p=0,05) and patients’ age (p=0,015).
Conclusion
Obtained results may indicate a clinical importance of analysis TP53 isoforms expression together with clinical data of patients.
Session topic: E-poster
Keyword(s): Acute myeloid leukemia, Expression, Flt3-ITD
Type: Publication Only
Background
TP53 encodes a tumor suppressor protein which consists of transactivation, DNA-binding and oligomerization domains. Due to alternative splicing it may exist in 13 different isoforms. Alternative splicing of intron 9 leads to production of 2 different proteins, p53β and p53γ, without oligomerization domain (stop codon is localized in exon 9b). These isoforms can be present in acute myeloid leukemia (AML) cells. p53β binds to BAX promoter and can induce apoptosis independent from p53 wt. It also regulates p53 activity. In AML high expression of p53β and p53γ proteins may play role in response to treatment by enhancing cells sensitivity to chemotherapy. It has been showed that patients have longer survival after treatment. NPM1 (nucleophosmin gene) mutations are frequent alterations in normal karyotype AML (NK AML). Until now 56 different mutations of exon 12 of NPM1 have been described, mostly insertions. The NPM protein plays an important role in cell cycle and apoptosis control. It cooperates with several proteins, including p53 and ARF. While patients with NPM1 mutations are stratified to favorable risk group, internal tandem duplications (ITD) in the fms-like tyrosine kinase-3 gene (FLT3) (i.e. FLT3ITD) are poor prognosis factors.
Aims
The aim of the study was to assess mutational status of NPM1/FLT3 in association with TP53beta and TP53gamma expression levels.
Methods
56 NK AML patients with NPM1 and/or FLT3ITD mutations were included in the study. Analysis of TP53β and TP53γ expression levels was possible only in 36 patients. Relative expression results were analyzed with ΔΔCt method, with ABL as a control gene and K562 cell line as a calibrator.
Results
In all 36 cases, TP53β and TP53γ transcripts were detected. 17 patients were NPM1+/FLT3-, 14 were NPM1+/FLT3+ and 5 were NPM1-/FLT3+. Assessed median expression level of TP53β was much higher (ΔΔCt 43,87) than TP53γ (ΔΔCt 10,52; p=0,000027). Furthermore, according to statistical analysis, expression level of TP53γ was significantly associated with NPM1/FLT3 mutations (p=0,008). We also classified patients according to median expression value of TP53 to two groups: with overexpression or with small expression. Median WBC count in patients with overexpression of both isoforms was higher (75,4 G/L) than in group where expression of both isoforms was below median value (30G/L). Expression level of TP53γ was also correlated to WBC (p=0,05) and patients’ age (p=0,015).
Conclusion
Obtained results may indicate a clinical importance of analysis TP53 isoforms expression together with clinical data of patients.
Session topic: E-poster
Keyword(s): Acute myeloid leukemia, Expression, Flt3-ITD
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