PROGNOSTIC IMPLICATIONS OF THE IDH1 SINGLE NUCLEOTIDE POLYMORPHISM RS11554137 IN PATIENTS WITH ACUTE MYELOID LEUKEMIA
(Abstract release date: 05/19/16)
EHA Library. Martynkevich I. 06/09/16; 132492; E943
Irina Martynkevich
Contributions
Contributions
Abstract
Abstract: E943
Type: Eposter Presentation
Background
Several studies have shown that synonymous single nucleotide polymorphisms directly impact gene function through various translational or post-translational mechanisms, such as altering mRNA binding, protein folding, the spliceosome, mRNA stability, or expression in general. Mutations in 132 codon of IDH1 gene are quite frequent event in acute myeloid leukemia (AML). Also, approximately 10% of AML patients were detected to have polymorphism rs11554137 in the 4th exon of IDH1 gene. Data concerning the impact on prognosis of polymorphism rs11554137 is still controversial.
Aims
To investigate the frequency and prognostic value of polymorphism rs11554137 in IDH1 gene, its combination with clinical hematological features and karyotype variant in AML pts.
Methods
The study included 112 pts with AML (median age - 55 years). In 103 pts (92.0%) was verified de novo AML and in 9 (8.0%) - secondary AML from preceding MDS or lymphoma. Cytogenetic analysis was performed on G-differentially stained chromosomes, so pts were divided into 4 groups: with normal karyotype (NK) - 52 (46.4%), favorable karyotype - 9 (8.0%), unfavorable karyotype - 16 (14.3%), with other chromosomal abnormalities - 35 (31.3%) pts. Screening of IDH1 gene aberrations was performed by real-time PCR with further analysis of melting curves.
Results
Polymorphism rs11554137 in IDH1 gene was detected in 7.1% (8 out of 112) of pts with AML. Distribution of pts with AML, depending on the morphological variants showed that polymorphism rs11554137 was more common in pts with M4 variant (5 of 20, p = 0.005). All pts with polymorphism rs11554137 had de novo AML. The median age of pts with polymorphism rs11554137 (58 years) was significantly higher than in pts without it (55 years) (p = 0.005). There was no significant differences when the number of white blood cells and platelets in PB, blasts in BM in pts with and without polymorphism rs11554137 was compared.Slightly more often polymorphism rs11554137 in IDH1 gene occured in pts with NK (5 of 8 pts; p = 0.334), 3 pts with polymorphism had unfavorable karyotype. None of the pts with favorable karyotype was detected to have polymorphism rs11554137. All pts with polymorphism rs11554137 in IDH1 gene were screened for mutations in FLT3, NPM1, NRAS, CKIT and DNMT3A genes. Only in 2 pts polymorphism rs11554137 in IDH1 gene was met singly. In the remaining pts (6 of 8) polymorphism rs11554137 was found simultaneously with mutations in other genes: DNMT3A+, FLT3-TKD+, NPM1+, FLT3-ITD+/DNMT3A+, FLT3-ITD+/FLT3-TKD+/DNMT3A+ and in 2 pts polymorphism rs11554137 was detected in combination with FLT3-ITD. We also investigated the prognostic value of polymorphism rs11554137 in IDH1 gene. Comparative analysis of median overall and relapse free survival in pts with and without polymorphism showed significant differences: 5.8 months and 12.8 months (p = 0.046) and 4.2 months and 9.5 months (p = 0.004) respectively.
Conclusion
Polymorphism rs11554137 in IDH1 gene is quite frequent event in pts with AML. It is usually associated with M4 variant of AML and higher median age as compared with pts without polymorphism. Significant prognostic potential of polymorphism rs11554137 in IDH1 gene allows to consider it as an unfavorable marker correlated with a high risk of relapse and poorer survival. Synonymous polymorphisms represent a special category of molecular aberrations that should be considered in the diagnosis and prognosis of AML pts.
Session topic: E-poster
Keyword(s): AML, Prognosis, SNP
Type: Eposter Presentation
Background
Several studies have shown that synonymous single nucleotide polymorphisms directly impact gene function through various translational or post-translational mechanisms, such as altering mRNA binding, protein folding, the spliceosome, mRNA stability, or expression in general. Mutations in 132 codon of IDH1 gene are quite frequent event in acute myeloid leukemia (AML). Also, approximately 10% of AML patients were detected to have polymorphism rs11554137 in the 4th exon of IDH1 gene. Data concerning the impact on prognosis of polymorphism rs11554137 is still controversial.
Aims
To investigate the frequency and prognostic value of polymorphism rs11554137 in IDH1 gene, its combination with clinical hematological features and karyotype variant in AML pts.
Methods
The study included 112 pts with AML (median age - 55 years). In 103 pts (92.0%) was verified de novo AML and in 9 (8.0%) - secondary AML from preceding MDS or lymphoma. Cytogenetic analysis was performed on G-differentially stained chromosomes, so pts were divided into 4 groups: with normal karyotype (NK) - 52 (46.4%), favorable karyotype - 9 (8.0%), unfavorable karyotype - 16 (14.3%), with other chromosomal abnormalities - 35 (31.3%) pts. Screening of IDH1 gene aberrations was performed by real-time PCR with further analysis of melting curves.
Results
Polymorphism rs11554137 in IDH1 gene was detected in 7.1% (8 out of 112) of pts with AML. Distribution of pts with AML, depending on the morphological variants showed that polymorphism rs11554137 was more common in pts with M4 variant (5 of 20, p = 0.005). All pts with polymorphism rs11554137 had de novo AML. The median age of pts with polymorphism rs11554137 (58 years) was significantly higher than in pts without it (55 years) (p = 0.005). There was no significant differences when the number of white blood cells and platelets in PB, blasts in BM in pts with and without polymorphism rs11554137 was compared.Slightly more often polymorphism rs11554137 in IDH1 gene occured in pts with NK (5 of 8 pts; p = 0.334), 3 pts with polymorphism had unfavorable karyotype. None of the pts with favorable karyotype was detected to have polymorphism rs11554137. All pts with polymorphism rs11554137 in IDH1 gene were screened for mutations in FLT3, NPM1, NRAS, CKIT and DNMT3A genes. Only in 2 pts polymorphism rs11554137 in IDH1 gene was met singly. In the remaining pts (6 of 8) polymorphism rs11554137 was found simultaneously with mutations in other genes: DNMT3A+, FLT3-TKD+, NPM1+, FLT3-ITD+/DNMT3A+, FLT3-ITD+/FLT3-TKD+/DNMT3A+ and in 2 pts polymorphism rs11554137 was detected in combination with FLT3-ITD. We also investigated the prognostic value of polymorphism rs11554137 in IDH1 gene. Comparative analysis of median overall and relapse free survival in pts with and without polymorphism showed significant differences: 5.8 months and 12.8 months (p = 0.046) and 4.2 months and 9.5 months (p = 0.004) respectively.
Conclusion
Polymorphism rs11554137 in IDH1 gene is quite frequent event in pts with AML. It is usually associated with M4 variant of AML and higher median age as compared with pts without polymorphism. Significant prognostic potential of polymorphism rs11554137 in IDH1 gene allows to consider it as an unfavorable marker correlated with a high risk of relapse and poorer survival. Synonymous polymorphisms represent a special category of molecular aberrations that should be considered in the diagnosis and prognosis of AML pts.
Session topic: E-poster
Keyword(s): AML, Prognosis, SNP
Abstract: E943
Type: Eposter Presentation
Background
Several studies have shown that synonymous single nucleotide polymorphisms directly impact gene function through various translational or post-translational mechanisms, such as altering mRNA binding, protein folding, the spliceosome, mRNA stability, or expression in general. Mutations in 132 codon of IDH1 gene are quite frequent event in acute myeloid leukemia (AML). Also, approximately 10% of AML patients were detected to have polymorphism rs11554137 in the 4th exon of IDH1 gene. Data concerning the impact on prognosis of polymorphism rs11554137 is still controversial.
Aims
To investigate the frequency and prognostic value of polymorphism rs11554137 in IDH1 gene, its combination with clinical hematological features and karyotype variant in AML pts.
Methods
The study included 112 pts with AML (median age - 55 years). In 103 pts (92.0%) was verified de novo AML and in 9 (8.0%) - secondary AML from preceding MDS or lymphoma. Cytogenetic analysis was performed on G-differentially stained chromosomes, so pts were divided into 4 groups: with normal karyotype (NK) - 52 (46.4%), favorable karyotype - 9 (8.0%), unfavorable karyotype - 16 (14.3%), with other chromosomal abnormalities - 35 (31.3%) pts. Screening of IDH1 gene aberrations was performed by real-time PCR with further analysis of melting curves.
Results
Polymorphism rs11554137 in IDH1 gene was detected in 7.1% (8 out of 112) of pts with AML. Distribution of pts with AML, depending on the morphological variants showed that polymorphism rs11554137 was more common in pts with M4 variant (5 of 20, p = 0.005). All pts with polymorphism rs11554137 had de novo AML. The median age of pts with polymorphism rs11554137 (58 years) was significantly higher than in pts without it (55 years) (p = 0.005). There was no significant differences when the number of white blood cells and platelets in PB, blasts in BM in pts with and without polymorphism rs11554137 was compared.Slightly more often polymorphism rs11554137 in IDH1 gene occured in pts with NK (5 of 8 pts; p = 0.334), 3 pts with polymorphism had unfavorable karyotype. None of the pts with favorable karyotype was detected to have polymorphism rs11554137. All pts with polymorphism rs11554137 in IDH1 gene were screened for mutations in FLT3, NPM1, NRAS, CKIT and DNMT3A genes. Only in 2 pts polymorphism rs11554137 in IDH1 gene was met singly. In the remaining pts (6 of 8) polymorphism rs11554137 was found simultaneously with mutations in other genes: DNMT3A+, FLT3-TKD+, NPM1+, FLT3-ITD+/DNMT3A+, FLT3-ITD+/FLT3-TKD+/DNMT3A+ and in 2 pts polymorphism rs11554137 was detected in combination with FLT3-ITD. We also investigated the prognostic value of polymorphism rs11554137 in IDH1 gene. Comparative analysis of median overall and relapse free survival in pts with and without polymorphism showed significant differences: 5.8 months and 12.8 months (p = 0.046) and 4.2 months and 9.5 months (p = 0.004) respectively.
Conclusion
Polymorphism rs11554137 in IDH1 gene is quite frequent event in pts with AML. It is usually associated with M4 variant of AML and higher median age as compared with pts without polymorphism. Significant prognostic potential of polymorphism rs11554137 in IDH1 gene allows to consider it as an unfavorable marker correlated with a high risk of relapse and poorer survival. Synonymous polymorphisms represent a special category of molecular aberrations that should be considered in the diagnosis and prognosis of AML pts.
Session topic: E-poster
Keyword(s): AML, Prognosis, SNP
Type: Eposter Presentation
Background
Several studies have shown that synonymous single nucleotide polymorphisms directly impact gene function through various translational or post-translational mechanisms, such as altering mRNA binding, protein folding, the spliceosome, mRNA stability, or expression in general. Mutations in 132 codon of IDH1 gene are quite frequent event in acute myeloid leukemia (AML). Also, approximately 10% of AML patients were detected to have polymorphism rs11554137 in the 4th exon of IDH1 gene. Data concerning the impact on prognosis of polymorphism rs11554137 is still controversial.
Aims
To investigate the frequency and prognostic value of polymorphism rs11554137 in IDH1 gene, its combination with clinical hematological features and karyotype variant in AML pts.
Methods
The study included 112 pts with AML (median age - 55 years). In 103 pts (92.0%) was verified de novo AML and in 9 (8.0%) - secondary AML from preceding MDS or lymphoma. Cytogenetic analysis was performed on G-differentially stained chromosomes, so pts were divided into 4 groups: with normal karyotype (NK) - 52 (46.4%), favorable karyotype - 9 (8.0%), unfavorable karyotype - 16 (14.3%), with other chromosomal abnormalities - 35 (31.3%) pts. Screening of IDH1 gene aberrations was performed by real-time PCR with further analysis of melting curves.
Results
Polymorphism rs11554137 in IDH1 gene was detected in 7.1% (8 out of 112) of pts with AML. Distribution of pts with AML, depending on the morphological variants showed that polymorphism rs11554137 was more common in pts with M4 variant (5 of 20, p = 0.005). All pts with polymorphism rs11554137 had de novo AML. The median age of pts with polymorphism rs11554137 (58 years) was significantly higher than in pts without it (55 years) (p = 0.005). There was no significant differences when the number of white blood cells and platelets in PB, blasts in BM in pts with and without polymorphism rs11554137 was compared.Slightly more often polymorphism rs11554137 in IDH1 gene occured in pts with NK (5 of 8 pts; p = 0.334), 3 pts with polymorphism had unfavorable karyotype. None of the pts with favorable karyotype was detected to have polymorphism rs11554137. All pts with polymorphism rs11554137 in IDH1 gene were screened for mutations in FLT3, NPM1, NRAS, CKIT and DNMT3A genes. Only in 2 pts polymorphism rs11554137 in IDH1 gene was met singly. In the remaining pts (6 of 8) polymorphism rs11554137 was found simultaneously with mutations in other genes: DNMT3A+, FLT3-TKD+, NPM1+, FLT3-ITD+/DNMT3A+, FLT3-ITD+/FLT3-TKD+/DNMT3A+ and in 2 pts polymorphism rs11554137 was detected in combination with FLT3-ITD. We also investigated the prognostic value of polymorphism rs11554137 in IDH1 gene. Comparative analysis of median overall and relapse free survival in pts with and without polymorphism showed significant differences: 5.8 months and 12.8 months (p = 0.046) and 4.2 months and 9.5 months (p = 0.004) respectively.
Conclusion
Polymorphism rs11554137 in IDH1 gene is quite frequent event in pts with AML. It is usually associated with M4 variant of AML and higher median age as compared with pts without polymorphism. Significant prognostic potential of polymorphism rs11554137 in IDH1 gene allows to consider it as an unfavorable marker correlated with a high risk of relapse and poorer survival. Synonymous polymorphisms represent a special category of molecular aberrations that should be considered in the diagnosis and prognosis of AML pts.
Session topic: E-poster
Keyword(s): AML, Prognosis, SNP
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