Contributions
Abstract: PB1705
Type: Publication Only
Background
Acute myeloid leukemia (AML) is a heterogeneous clonal disorder with a presence of diverse genetic abnormalities in hematopoietic stem cells. SRSF2 encodes serine/arginine-rich splicing factor 2, important for splice-site selection, spliceosome assembly, constitutive and alternative splicing. More than 90% of human genes undergo alternative splicing to make various protein isoforms. TP53 gene, that encodes a tumor suppressor protein, may be translated into 13 different isoforms due to alternative splicing. Alternative splicing of its intron 9 can produce 2 different proteins: p53β and p53γ, without oligomerization domain (stop codon is localized in exon 9b).
Aims
The aim of the study was to assess mutational status of SRSF2 as well as TP53β and TP53γ expression levels in association with hematological and clinical features of patients with AML.
Methods
49 AML patients with normal karyotype were included in the study. SRSF2 gene mutations in codon 95 were analyzed by direct sequencing. TP53β and TP53γ expression levels were assessed with real time PCR. Expression levels were analyzed with ΔΔCt method, with ABL as a control gene and K562 cell line as a calibrator.
Results
TP53β and TP53γ transcripts were detected in all patients. 5 patients carried mutation in SRSF2. Mutation status of SRSF2 had no statistical significance to overall survival (p=0,36). Assessed median expression level was much higher for TP53β than TP53γ (ΔΔCt 44,04 vs 9,42, respectively; p<0,05). Furthermore, expression level of TP53γ was significantly associated with SRSF2 mutations (p=0,021); patients with mutation had lower expression level. Patients were also classified into two groups, according to median expression value of TP53: with overexpression or with low expression of TP53β/γ. Kaplan-Meier estimation showed statistically significant difference in overall survival between the groups - longer for patients with overexpression of TP53γ isoform (p=0,03).
Conclusion
The above results may suggest a clinical importance of simultaneous analysis of TP53 isoform expression and SRSF2 gene mutations. It may be hypothesized that a changed sequence of the SRSF2 gene regulates TP53γ expression and, as a consequence, regulates the cell cycle and overall survival.
Session topic: 3. Acute myeloid leukemia - Biology & Translational Research
Keyword(s): AML, Gene expression
Abstract: PB1705
Type: Publication Only
Background
Acute myeloid leukemia (AML) is a heterogeneous clonal disorder with a presence of diverse genetic abnormalities in hematopoietic stem cells. SRSF2 encodes serine/arginine-rich splicing factor 2, important for splice-site selection, spliceosome assembly, constitutive and alternative splicing. More than 90% of human genes undergo alternative splicing to make various protein isoforms. TP53 gene, that encodes a tumor suppressor protein, may be translated into 13 different isoforms due to alternative splicing. Alternative splicing of its intron 9 can produce 2 different proteins: p53β and p53γ, without oligomerization domain (stop codon is localized in exon 9b).
Aims
The aim of the study was to assess mutational status of SRSF2 as well as TP53β and TP53γ expression levels in association with hematological and clinical features of patients with AML.
Methods
49 AML patients with normal karyotype were included in the study. SRSF2 gene mutations in codon 95 were analyzed by direct sequencing. TP53β and TP53γ expression levels were assessed with real time PCR. Expression levels were analyzed with ΔΔCt method, with ABL as a control gene and K562 cell line as a calibrator.
Results
TP53β and TP53γ transcripts were detected in all patients. 5 patients carried mutation in SRSF2. Mutation status of SRSF2 had no statistical significance to overall survival (p=0,36). Assessed median expression level was much higher for TP53β than TP53γ (ΔΔCt 44,04 vs 9,42, respectively; p<0,05). Furthermore, expression level of TP53γ was significantly associated with SRSF2 mutations (p=0,021); patients with mutation had lower expression level. Patients were also classified into two groups, according to median expression value of TP53: with overexpression or with low expression of TP53β/γ. Kaplan-Meier estimation showed statistically significant difference in overall survival between the groups - longer for patients with overexpression of TP53γ isoform (p=0,03).
Conclusion
The above results may suggest a clinical importance of simultaneous analysis of TP53 isoform expression and SRSF2 gene mutations. It may be hypothesized that a changed sequence of the SRSF2 gene regulates TP53γ expression and, as a consequence, regulates the cell cycle and overall survival.
Session topic: 3. Acute myeloid leukemia - Biology & Translational Research
Keyword(s): AML, Gene expression