CLINICAL SIGNIFICANCE OF DIFFERENT GATA-2 MUTATION TYPE IN ACUTE MYELOID LEUKEMIA
(Abstract release date: 05/21/15)
EHA Library. Zhang S. 06/12/15; 102786; PB1630
Disclosure(s): The First Affiliated Hospital of Nanjing Medical University
Sujiang Zhang
Contributions
Contributions
Abstract
Abstract: PB1630
Type: Publication Only
Background
Cytogenetic and gene abnormalities are considered to be the most important prognostic factors of acute myeloid leukemia(AML) patients. Gene mutations such as internal tandem duplications (ITDs) or tyrosine kinase domain (TKD) of FMS-like tyrosine kinase 3 (FLT3), C-KIT, neuroblastoma RAS viral oncogene homolog gene (NRAS) have been considered to belong to class ? involving signal transduction, nucleophosmin gene (NPM1), the CCAAT/enhancer binding protein α gene (CEBPA) or the mixed-lineage leukemia (MLL)gene, which can be affected either through chromosomal translocation or via an intragenic partial tandem duplications (PTDs) to form a fusion gene to class ? those causing impaired differentiation. GATA-2 is a zinc-finger(ZF) transcription factor and play important roles in hematopoiesis in many cell lineages.
Aims
To evaluate the prognostic value of GATA-2 mutation in acute myeloid leukemia (AML) patients, we performed sequence analysis to see if GATA-2 mutation play important role in AML leukemogenesis.
Methods
We performed sequence analysis to detect GATA-2 mutation in 135 AML patients. We also performed luciferase assay and Western-Blot assay to analyze the biological function of mutant GATA-2.
Results
A total of 5 (3.7%) different GATA-2 mutations were detected in 135 patients. The mutation types of GATA-2 were GATA-2 W10C(tgg>tgt, Trp→Cys), GATA-2 S277N(agc>aac, Ser→Asn), GATA-2 P304H(cct>cat, Pro→His), GATA-2 R362Q(cga>caa, Arg→Gln), GATA-2 V369A(gtc>gcc, Val→Ala). Luciferase assay showed the transcription activity of GATA-2 G320D was significantly lower than that of wt GATA-2(P<0.05), whereas the activity of GATA-2 P304H and GATA-2 R362Q was slightly lower than wtGATA-2 (P>0.05). The result of Western-Blot showed that the expression of GATA-2 protein in GATA-2 P304H(P=0.002) was significantly higher while GATA-2 R362Q or GATA-2 G320D mutants was lower than wt GATA-2 (P=0.02 and P=0.004, respectively).
Summary
GATA-2 mutation is a rare mutation in AML patients. The mutations located in zinc-finger domain may contribute to AML leukemogenesis.
Keyword(s): Acute myeloid leukemia, GATA-2, Mutation
Type: Publication Only
Background
Cytogenetic and gene abnormalities are considered to be the most important prognostic factors of acute myeloid leukemia(AML) patients. Gene mutations such as internal tandem duplications (ITDs) or tyrosine kinase domain (TKD) of FMS-like tyrosine kinase 3 (FLT3), C-KIT, neuroblastoma RAS viral oncogene homolog gene (NRAS) have been considered to belong to class ? involving signal transduction, nucleophosmin gene (NPM1), the CCAAT/enhancer binding protein α gene (CEBPA) or the mixed-lineage leukemia (MLL)gene, which can be affected either through chromosomal translocation or via an intragenic partial tandem duplications (PTDs) to form a fusion gene to class ? those causing impaired differentiation. GATA-2 is a zinc-finger(ZF) transcription factor and play important roles in hematopoiesis in many cell lineages.
Aims
To evaluate the prognostic value of GATA-2 mutation in acute myeloid leukemia (AML) patients, we performed sequence analysis to see if GATA-2 mutation play important role in AML leukemogenesis.
Methods
We performed sequence analysis to detect GATA-2 mutation in 135 AML patients. We also performed luciferase assay and Western-Blot assay to analyze the biological function of mutant GATA-2.
Results
A total of 5 (3.7%) different GATA-2 mutations were detected in 135 patients. The mutation types of GATA-2 were GATA-2 W10C(tgg>tgt, Trp→Cys), GATA-2 S277N(agc>aac, Ser→Asn), GATA-2 P304H(cct>cat, Pro→His), GATA-2 R362Q(cga>caa, Arg→Gln), GATA-2 V369A(gtc>gcc, Val→Ala). Luciferase assay showed the transcription activity of GATA-2 G320D was significantly lower than that of wt GATA-2(P<0.05), whereas the activity of GATA-2 P304H and GATA-2 R362Q was slightly lower than wtGATA-2 (P>0.05). The result of Western-Blot showed that the expression of GATA-2 protein in GATA-2 P304H(P=0.002) was significantly higher while GATA-2 R362Q or GATA-2 G320D mutants was lower than wt GATA-2 (P=0.02 and P=0.004, respectively).
Summary
GATA-2 mutation is a rare mutation in AML patients. The mutations located in zinc-finger domain may contribute to AML leukemogenesis.
Keyword(s): Acute myeloid leukemia, GATA-2, Mutation
Abstract: PB1630
Type: Publication Only
Background
Cytogenetic and gene abnormalities are considered to be the most important prognostic factors of acute myeloid leukemia(AML) patients. Gene mutations such as internal tandem duplications (ITDs) or tyrosine kinase domain (TKD) of FMS-like tyrosine kinase 3 (FLT3), C-KIT, neuroblastoma RAS viral oncogene homolog gene (NRAS) have been considered to belong to class ? involving signal transduction, nucleophosmin gene (NPM1), the CCAAT/enhancer binding protein α gene (CEBPA) or the mixed-lineage leukemia (MLL)gene, which can be affected either through chromosomal translocation or via an intragenic partial tandem duplications (PTDs) to form a fusion gene to class ? those causing impaired differentiation. GATA-2 is a zinc-finger(ZF) transcription factor and play important roles in hematopoiesis in many cell lineages.
Aims
To evaluate the prognostic value of GATA-2 mutation in acute myeloid leukemia (AML) patients, we performed sequence analysis to see if GATA-2 mutation play important role in AML leukemogenesis.
Methods
We performed sequence analysis to detect GATA-2 mutation in 135 AML patients. We also performed luciferase assay and Western-Blot assay to analyze the biological function of mutant GATA-2.
Results
A total of 5 (3.7%) different GATA-2 mutations were detected in 135 patients. The mutation types of GATA-2 were GATA-2 W10C(tgg>tgt, Trp→Cys), GATA-2 S277N(agc>aac, Ser→Asn), GATA-2 P304H(cct>cat, Pro→His), GATA-2 R362Q(cga>caa, Arg→Gln), GATA-2 V369A(gtc>gcc, Val→Ala). Luciferase assay showed the transcription activity of GATA-2 G320D was significantly lower than that of wt GATA-2(P<0.05), whereas the activity of GATA-2 P304H and GATA-2 R362Q was slightly lower than wtGATA-2 (P>0.05). The result of Western-Blot showed that the expression of GATA-2 protein in GATA-2 P304H(P=0.002) was significantly higher while GATA-2 R362Q or GATA-2 G320D mutants was lower than wt GATA-2 (P=0.02 and P=0.004, respectively).
Summary
GATA-2 mutation is a rare mutation in AML patients. The mutations located in zinc-finger domain may contribute to AML leukemogenesis.
Keyword(s): Acute myeloid leukemia, GATA-2, Mutation
Type: Publication Only
Background
Cytogenetic and gene abnormalities are considered to be the most important prognostic factors of acute myeloid leukemia(AML) patients. Gene mutations such as internal tandem duplications (ITDs) or tyrosine kinase domain (TKD) of FMS-like tyrosine kinase 3 (FLT3), C-KIT, neuroblastoma RAS viral oncogene homolog gene (NRAS) have been considered to belong to class ? involving signal transduction, nucleophosmin gene (NPM1), the CCAAT/enhancer binding protein α gene (CEBPA) or the mixed-lineage leukemia (MLL)gene, which can be affected either through chromosomal translocation or via an intragenic partial tandem duplications (PTDs) to form a fusion gene to class ? those causing impaired differentiation. GATA-2 is a zinc-finger(ZF) transcription factor and play important roles in hematopoiesis in many cell lineages.
Aims
To evaluate the prognostic value of GATA-2 mutation in acute myeloid leukemia (AML) patients, we performed sequence analysis to see if GATA-2 mutation play important role in AML leukemogenesis.
Methods
We performed sequence analysis to detect GATA-2 mutation in 135 AML patients. We also performed luciferase assay and Western-Blot assay to analyze the biological function of mutant GATA-2.
Results
A total of 5 (3.7%) different GATA-2 mutations were detected in 135 patients. The mutation types of GATA-2 were GATA-2 W10C(tgg>tgt, Trp→Cys), GATA-2 S277N(agc>aac, Ser→Asn), GATA-2 P304H(cct>cat, Pro→His), GATA-2 R362Q(cga>caa, Arg→Gln), GATA-2 V369A(gtc>gcc, Val→Ala). Luciferase assay showed the transcription activity of GATA-2 G320D was significantly lower than that of wt GATA-2(P<0.05), whereas the activity of GATA-2 P304H and GATA-2 R362Q was slightly lower than wtGATA-2 (P>0.05). The result of Western-Blot showed that the expression of GATA-2 protein in GATA-2 P304H(P=0.002) was significantly higher while GATA-2 R362Q or GATA-2 G320D mutants was lower than wt GATA-2 (P=0.02 and P=0.004, respectively).
Summary
GATA-2 mutation is a rare mutation in AML patients. The mutations located in zinc-finger domain may contribute to AML leukemogenesis.
Keyword(s): Acute myeloid leukemia, GATA-2, Mutation
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