ASSOCIATIONS OF IL-1, IL-4 AND TGF-Β1 POLYMORPHISMS WITH CYTOGENETIC PROFILES IN PATIENTS WITH MULTIPLE MYELOMA
(Abstract release date: 05/18/17)
EHA Library. Pavlova A. 05/18/17; 182658; PB1944
Ms. Anastasia Pavlova
Contributions
Contributions
Abstract
Abstract: PB1944
Type: Publication Only
Background
Multiple myeloma (MM) is a plasma cell malignancy characterized by complex cytogenetic and molecular genetic aberrations. Those cytogenetic abnormalities occur at different stages of the disease. The chromosome ploidy status and Ig rearrangements are two genetic criteria that are used to help stratify patients into prognostic groups.
Aims
The aim of the study was to analyse correlation between cytogenetic profiles and some cytokine genotypes in 24 patients with MM (Caucasoid inhabitants of the North-West region of Russia).
Methods
Genomic DNA was extracted from the peripheral blood; gene genotyping (IL-4, TGF-β1, IL-1α, IL-1β) was performed by PCR-SSP; study of cytogenetic abnormalities was performed by standard GTG-method and interphase FISH analyses with DNA probes: LSI 13(RB1)13q14, IGH/CCND1, IGH/FGFR3, LSI TP53 (17q13.1); p-values less than 0.05 were considered statistically significant.
Results
Previous results allow us to describe some cytokine genotype markers associated with the development of MM (IL-1α -889 TT, IL-1β +3962 TT, IL-6 -174 GG and IL-6 nt565 GG; gr. 1) as additional negative prognostic markers but IL-4 -33 CC and TGF-β1 codon 25 GG genotypes as additional positive prognostic markers (gr. 2). However, in some MM patients we found presence of negative and positive markers together (mixed markers; gr. 3). We analyzed cytogenetic profiles in MM patients with different prognostic markers in their genotypes (Table).
| Genotypes with prognostic markers | Abnormal cytogenetic profile | Normal cytogenetic profile |
| 1st gr. - MM patients with negative prognostic markers in genotype: IL-1a -889TT, IL-1b +3962TT, IL-6 -174GG, IL-6 nt565GG | 0.778* | 0.222 |
| 2nd gr. - MM patients with positive prognostic markers in genotype: IL-4 -33CC, TGF-b1 codon25GG | 0.111* | 0.889* |
| 3rd gr. - MM patients with mixed prognostic markers in genotype | 0.667 | 0.333 |
| *- p<0.05 | ||
The frequency of abnormal cytogenetic transformations in the 2nd gr. was noticeably lower compare to patients from the 1st and 3rd gr. (0.11 vs. 0.78 vs. 0.67 respectively; p<0.05). Similarly, significant differencies in the frequency between patients with positive prognostic markers and normal cytogeneic profile (0.89) compare to MM patients with negative (0.22) or mixed (0.33) genotypes but normal cytogenetic profiles were also observed (p<0.05). In the 1st gr. frequency of cytogenetic abnormalities was noticeably higher compare to patients with normal profile (0.78 vs. 0.22; p<0.05). Vice versa, in patients with positive prognostic markers in the genotype frequency of normal cytogenetic profiles was remarkably higher (0.89) compare to patients with aberrations (0.11; p<0.05).
Conclusion
Thus, our results allow to describe IL-1α -889 TT, IL-1β +3962 TT, IL-6 -174 GG and IL-6 nt565 GG as markers associated with the presence of cytogenetic abnormalities in MM patient cells. However, IL-4 -33 CC and TGF-β1 codon 25 GG indicate the normal cytogenetic profile in patients with MM from the North-West region of Russia. Although, if MM patients have both negative and positive prognostic markers associated with the development of multiple myeloma (mixed genotype) it seems that the chance of finding cytogenetic abnormalities is much higher compare to patients with positive prognostic markers only.
Session topic: 13. Myeloma and other monoclonal gammopathies - Biology
Keyword(s): Polymorphism, Multiple Myeloma, Cytokine, Cytogenetics
Abstract: PB1944
Type: Publication Only
Background
Multiple myeloma (MM) is a plasma cell malignancy characterized by complex cytogenetic and molecular genetic aberrations. Those cytogenetic abnormalities occur at different stages of the disease. The chromosome ploidy status and Ig rearrangements are two genetic criteria that are used to help stratify patients into prognostic groups.
Aims
The aim of the study was to analyse correlation between cytogenetic profiles and some cytokine genotypes in 24 patients with MM (Caucasoid inhabitants of the North-West region of Russia).
Methods
Genomic DNA was extracted from the peripheral blood; gene genotyping (IL-4, TGF-β1, IL-1α, IL-1β) was performed by PCR-SSP; study of cytogenetic abnormalities was performed by standard GTG-method and interphase FISH analyses with DNA probes: LSI 13(RB1)13q14, IGH/CCND1, IGH/FGFR3, LSI TP53 (17q13.1); p-values less than 0.05 were considered statistically significant.
Results
Previous results allow us to describe some cytokine genotype markers associated with the development of MM (IL-1α -889 TT, IL-1β +3962 TT, IL-6 -174 GG and IL-6 nt565 GG; gr. 1) as additional negative prognostic markers but IL-4 -33 CC and TGF-β1 codon 25 GG genotypes as additional positive prognostic markers (gr. 2). However, in some MM patients we found presence of negative and positive markers together (mixed markers; gr. 3). We analyzed cytogenetic profiles in MM patients with different prognostic markers in their genotypes (Table).
| Genotypes with prognostic markers | Abnormal cytogenetic profile | Normal cytogenetic profile |
| 1st gr. - MM patients with negative prognostic markers in genotype: IL-1a -889TT, IL-1b +3962TT, IL-6 -174GG, IL-6 nt565GG | 0.778* | 0.222 |
| 2nd gr. - MM patients with positive prognostic markers in genotype: IL-4 -33CC, TGF-b1 codon25GG | 0.111* | 0.889* |
| 3rd gr. - MM patients with mixed prognostic markers in genotype | 0.667 | 0.333 |
| *- p<0.05 | ||
The frequency of abnormal cytogenetic transformations in the 2nd gr. was noticeably lower compare to patients from the 1st and 3rd gr. (0.11 vs. 0.78 vs. 0.67 respectively; p<0.05). Similarly, significant differencies in the frequency between patients with positive prognostic markers and normal cytogeneic profile (0.89) compare to MM patients with negative (0.22) or mixed (0.33) genotypes but normal cytogenetic profiles were also observed (p<0.05). In the 1st gr. frequency of cytogenetic abnormalities was noticeably higher compare to patients with normal profile (0.78 vs. 0.22; p<0.05). Vice versa, in patients with positive prognostic markers in the genotype frequency of normal cytogenetic profiles was remarkably higher (0.89) compare to patients with aberrations (0.11; p<0.05).
Conclusion
Thus, our results allow to describe IL-1α -889 TT, IL-1β +3962 TT, IL-6 -174 GG and IL-6 nt565 GG as markers associated with the presence of cytogenetic abnormalities in MM patient cells. However, IL-4 -33 CC and TGF-β1 codon 25 GG indicate the normal cytogenetic profile in patients with MM from the North-West region of Russia. Although, if MM patients have both negative and positive prognostic markers associated with the development of multiple myeloma (mixed genotype) it seems that the chance of finding cytogenetic abnormalities is much higher compare to patients with positive prognostic markers only.
Session topic: 13. Myeloma and other monoclonal gammopathies - Biology
Keyword(s): Polymorphism, Multiple Myeloma, Cytokine, Cytogenetics
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