Contributions
Abstract: PB1772
Type: Publication Only
Background
Generally, chronic lymphocytic leukemia (CLL) is considered to be a non-radiogenic form of leukemia. We previously found some clinical and biological features of CLL in group of clean-up workers of Chornobyl NPP accident indicated unfavorable disease course, such as high frequency of solid tumors and Richter transformation, mainly unmutated status of heavy chain variable region (IGHV) genes with increased usage of IGHV1-69 and IGHV3-21 (Abramenko et al., 2008). Analysis of genetic features of leukemic cells in IR-exposed CLL patients may provide an additional data on the possible causal relationship with IR.
Aims
the aim of the study was to analyze TP53, NOTCH1 and SF3B1 mutations in CLL patients, sufferers of Chornobyl NPP accident to clarify the possible pathogenetic relationship between IR and CLL development
Methods
Results
We found TP53 and SF3B1 mutations with similar incidence in both groups – in 11.3% and 10.0% of IR-exposed patients, and in 12.7% and 11.5% of IR non-exposed CLL patients, respectively. In contrast, NOTCH1 mutations were found with significantly lower frequency in IR-exposed patients in comparison with the control group (6.7% vs 17.7%; p=0.012). Some other features were found among IR-exposed CLL patients also. Specifically, TP53 mutations were seen with equal frequency among mutated (11.1%) and unmutated (11.8%) IGHV cases in IR-exposed CLL patients, while the tendency to prevalence of TP53 mutations in unmutated compared with mutated IGHV cases was found in the control group (14.1% and 5.6%, correspondingly; p=0.178). In IR-exposed group SF3B1 mutations were combined with mutations in TP53 almost in half of detected cases. In opposite, in the control group we observed reported earlier mutual exclusivity between SF3B1 and TP53 lesions (p=0.001 in comparison between observed groups). Among IR-exposed CLL patients we found two different cases with identical rare mutation of TP53 gene - c.665C>T substitution leading to change proline for leucine at codon 222 (Pro222Leu). This substitution is very likely to represent inherited TP53 mutation, which may influence CLL development under IR exposure.
Conclusion
Session topic: 5. Chronic lymphocytic leukemia and related disorders - Biology
Keyword(s): SNP, P53, Notch, Chronic Lymphocytic Leukemia
Abstract: PB1772
Type: Publication Only
Background
Generally, chronic lymphocytic leukemia (CLL) is considered to be a non-radiogenic form of leukemia. We previously found some clinical and biological features of CLL in group of clean-up workers of Chornobyl NPP accident indicated unfavorable disease course, such as high frequency of solid tumors and Richter transformation, mainly unmutated status of heavy chain variable region (IGHV) genes with increased usage of IGHV1-69 and IGHV3-21 (Abramenko et al., 2008). Analysis of genetic features of leukemic cells in IR-exposed CLL patients may provide an additional data on the possible causal relationship with IR.
Aims
the aim of the study was to analyze TP53, NOTCH1 and SF3B1 mutations in CLL patients, sufferers of Chornobyl NPP accident to clarify the possible pathogenetic relationship between IR and CLL development
Methods
Results
We found TP53 and SF3B1 mutations with similar incidence in both groups – in 11.3% and 10.0% of IR-exposed patients, and in 12.7% and 11.5% of IR non-exposed CLL patients, respectively. In contrast, NOTCH1 mutations were found with significantly lower frequency in IR-exposed patients in comparison with the control group (6.7% vs 17.7%; p=0.012). Some other features were found among IR-exposed CLL patients also. Specifically, TP53 mutations were seen with equal frequency among mutated (11.1%) and unmutated (11.8%) IGHV cases in IR-exposed CLL patients, while the tendency to prevalence of TP53 mutations in unmutated compared with mutated IGHV cases was found in the control group (14.1% and 5.6%, correspondingly; p=0.178). In IR-exposed group SF3B1 mutations were combined with mutations in TP53 almost in half of detected cases. In opposite, in the control group we observed reported earlier mutual exclusivity between SF3B1 and TP53 lesions (p=0.001 in comparison between observed groups). Among IR-exposed CLL patients we found two different cases with identical rare mutation of TP53 gene - c.665C>T substitution leading to change proline for leucine at codon 222 (Pro222Leu). This substitution is very likely to represent inherited TP53 mutation, which may influence CLL development under IR exposure.
Conclusion
Session topic: 5. Chronic lymphocytic leukemia and related disorders - Biology
Keyword(s): SNP, P53, Notch, Chronic Lymphocytic Leukemia