cytogenetic changes
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2021 ◽  
Vol 78 (6) ◽  
pp. 434-441
Author(s):  
Ivan Korshikov ◽  
◽  
Yuliia Bilonozhko ◽  
Volodymyr Hrabovyi ◽  
◽  
...  

Information on cytogenetic changes in the seed offspring of old-aged trees is insufficient and inconsistent. In our studies, 150–200-year old trees of Picea abies and Pinus pallasiana were used. We analyzed peculiarities of their karyotype, nucleus-forming region, and nucleolus in the cells of seedlings of P. abies and P. pallasiana emerged from seeds in natural populations and plantations of introduced plants. As a result, age-dependent cytogenetic disorders were observed, such as the chromosome bridges, lag, premature segregation, and agglutination. Peculiarities with regard to number and structure of secondary chromosome constriction are demonstrated. The identified properties of the cell structure of seeds of old-aged trees of P. abies and P. pallasiana indicate that more resources are needed to maintain their protein synthesis at a normal level. The increased number of abnormalities indicates a significant impact of accumulated intracellular metabolites and cytopathological phenomena in mother plants on the quality of seed offspring.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3380-3380
Author(s):  
Hiroaki Shimizu ◽  
Junichi Mukae ◽  
Naoki Shingai ◽  
Takashi Toya ◽  
Yuho Najima ◽  
...  

Abstract Background: Additional cytogenetic abnormalities (ACA), the most frequent form of cytogenetic changes, are considered as a result of genetic instability and clonal evolution of leukemia cells. Recently, we described that ACA at the first relapse was associated with the significantly lower second complete remission (CR2) rate and poor survival in adult acute myeloid leukemia (AML) patients (Hematol Oncol. 2018;36:252-257). However, the prognostic impact of ACA after allogeneic stem cell transplant (allo-SCT) has not been elucidated in adult AML patients. Patients and methods: Of the 145 adult AML patients who underwent the first allo-SCT in CR2 between 1997 and 2019, 98 patients whose cytogenetic abnormality data both at diagnosis and at the first relapse were available were included in this study. Cytogenetic changes between at diagnosis and the first relapse were classified into four groups: (1) no change, (2) ACA was acquired at the first relapse, (3) cytogenetic abnormalities observed at diagnosis were reduced or had disappeared at the first relapse, and (4) cytogenetic abnormalities observed at diagnosis were reduced or had disappeared, and completely different ACA was acquired at the first relapse. In this study, groups 2 and 4 were defined as ACA acquisition. Overall survival (OS) was defined as the interval from the date of transplant to the date of death. Fisher's exact test was used to compare binary variables. The cumulative incidence (CI) of non-relapse mortality (NRM) and relapse were evaluated with Gray's test, considering relapse and NRM as a competing risk, respectively. OS was estimated with the Kaplan-Meier method and compared using the log-rank test. Factors associated with at least borderline significance (p < 0.20) in univariate analyses were subjected to multivariate analysis. The Cox and Fine-Gray proportional hazard model were used for multivariate analysis of prognostic and risk factors, respectively. Values of p < 0.05 were considered to indicate statistical significance. Results: Of the 98 patients included in this study, 57 were male, and 41 were female. The median age at transplant was 45 years (range, 17-71 years). The median duration of CR1 was 12.4 months (range, 1.3-70.3 months) and cytogenetic risk groups were good, intermediate, and poor in 26 (27%), 70 (71%), and two patients (2%), respectively. Donor types were related, unrelated, and cord blood in 23 (24%), 59 (60%), and 16 patients (16%), respectively, and 86 (87%) and 61 patients (62%) were conditioned with myeloablative and total body irradiation-containing regimens, respectively. According to the definition described above, 20 patients (20%) acquired ACA at the first relapse. There was no significant difference in baseline characteristics and transplant procedures between patients with and without ACA acquisition. The OS rates were not significantly different between two groups (55% vs. 72% at three years after transplant; p = 0.28). The CI of relapse was significantly higher in patients with ACA acquisition than those without ACA acquisition (59% vs. 15%; p < 0.01), while the CI of NRM were not significantly different between two groups (5% vs. 19%; p = 0.17). Multivariate analysis for OS revealed that age over 50 years (hazard ratio [HR] = 2.4; p < 0.01), but not ACA acquisition, was identified as an independent prognostic factor. ACA acquisition (HR = 4.7; p < 0.01) was extracted as an independent risk factor of relapse, while use of reduced intensity conditioning regimens (HR = 3.1; p = 0.03) and more than or equal to 1 of performance status at transplant (HR = 2.7; p = 0.04) showed independent risks of NRM. The similar OS rates between two groups might resulted from an offset of the lower relapse rate with the higher NRM rate in patients without ACA acquisition despite not reaching statistical significance. This increasing NRM rates in those without ACA acquisition was potentially associated with use of reduced intensity conditioning regimens in larger proportion (0% vs. 15%; p = 0.12). Conclusion: These findings suggested that ACA acquisition at the first relapse was associated with a higher risk of relapse even after allo-SCT in CR2 in adult AML patients. As AML cells with ACA acquisition was resistant to not only chemotherapy but also graft-versus-leukemia effect, innovative therapeutic strategy is warranted. Disclosures Handa: Janssen: Honoraria; Kyowa Kirin: Research Funding; Takeda: Honoraria, Research Funding; BMS: Honoraria; Chugai: Research Funding; Ono: Honoraria; Sanofi: Honoraria, Research Funding; Abbvie: Honoraria; MSD: Research Funding; Shionogi: Research Funding; Celgene: Honoraria, Research Funding; Daiichi Sankyo: Research Funding.


2021 ◽  
pp. 209-214
Author(s):  
N. Ilyinskikh ◽  
E. Ilyinskikh ◽  
Filatova

Purpose: to study the duration of the preservation of the cytogenetic effects of tickborne encephalitis (TBE) in individuals infected with the Opisthorchis felineus (OF) helminth, which differ in alleles of the glutathione-S-transferase enzyme genes. Methods: the objects of the study were patients with tick-borne encephalitis in whom the frequencies of micronucleated lymphocytes were detected. All examined patients were subdivided into two groups: TBE patients non-infected with OF, and TBE patients infected with OF. Multiplex PCR was used to analyze the GSTM1 and GSTT1 genes. Results: patients with TBE, infected with OF, had a significantly lower increase in the level of cytogenetic disorders than patients with TBE without OF infection; at the same time, the restoration of the cytogenetic norm in this group was not reached, and there was no association between the frequency of micronucleated lymphocytes and different variants of the glutathione-S-transferase enzyme genes. Conclusion: the frequency of cytogenetic changes in TBE patients infected with OF are significantly less than one in patients with TBE without OF infection. Polymorphism in the genes of the enzyme glutathione-S-transferase does not have significant effect on the cytogenetic disorders in patients with TBE with OF infection.


2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Jacek Pietrzak ◽  
Marek Mirowski ◽  
Rafał Świechowski ◽  
Damian Wodziński ◽  
Agnieszka Wosiak ◽  
...  

Acute myeloid leukemia is a group of hematological neoplasms characterized by a heterogeneous course and high mortality. The important factor in the neoplastic process is metalloproteinases, proteolytic enzymes capable of degrading various components of the extracellular matrix, which take an active part in modifying the functioning of the cell, including transformation to cancer cell. They interact with numerous signaling pathways responsible for the process of cell growth, proliferation, or apoptosis. In the present study, changes in the expression of MMP2, MMP9, and MMP16 genes between patients with AML and people without cancer were examined. The impact of cytogenetic changes in neoplastic cells on the expression level of MMP2, MMP9, and MMP16 was also assessed, as well as the impact of the altered expression on the effectiveness of the first cycle of remission-inducing therapy. To evaluate the expression of all studied genes MMP2, MMP9, and MMP16, SYBR Green-based real-time PCR method was used; the reference gene was GAPDH. For two investigated genes MMP2 and MMP16, the lower expression level was observed in patients with AML when compared to healthy people. The MMP9 gene expression level did not differ between patients with AML and healthy individuals which may indicate a different regulation of gene expression in acute myeloid leukemia. However, no correlation was observed between the genes’ expression of all tested metalloproteinases and the result of cytoreductive treatment or the presence of cytogenetic changes. The obtained results show that the expression of MMP2 and MMP16 genes is reduced while the expression of MMP9 is unchanged in patients with acute myeloid leukemia. This may indicate a different regulation of the expression of these genes, and possible disruptions in gene transcription or posttranscriptional mechanisms in the MMP2 and MMP16 genes, however, do not affect the level of MMP9 expression. Obtained results in AML patients are in contrary to various types of solid tumors where increased expression is usually observed.


2021 ◽  
Vol 15 (2) ◽  
pp. 79-89
Author(s):  
Wanzi Chen ◽  
Jinghui Yang ◽  
Ping Chen

Abstract Background Patients diagnosed with acute myeloid leukemia (AML) in childhood have a poor prognosis. A better understanding of prognostic factors will assist patients and clinicians in making difficult treatment decisions. Objectives To understand further the cytogenetic characteristics of and reassess the prognostic value of cytogenetic abnormalities in childhood AML. Methods Conventional karyotypes of 107 children with AML were analyzed retrospectively. The cases were divided into 4 groups based on genetic rearrangements; namely patients with: t(15;17)/PML-RARA; t(8;21)/RUNX1-RUNX1T1 or inv(16)(p13;q22) and t(16;16)/CBFB-MYH11; −7 or complex karyotypes; normal karyotypes or other cytogenetic changes. Differences in age, sex, leukocyte count, event-free survival (EFS), and overall survival (OS) were analyzed. Results All French-American-British (FAB) subtypes of AML were detected in 107 patients. We successfully cultured 81 of 107 bone marrow specimens, of which 60 cases had abnormal karyotypes. The most common abnormal karyotypes were t(8;21) (17/81 cases), followed by t(15;17) (13/81 cases), –X/Y (10/81 cases). There were no significant differences (P > 0.05) in age, sex, or leukocyte counts between the 4 groups. The differences in 3-year EFS and OS between each pair were significant, except for groups of patients with t(8;21)/RUNX1-RUNX1T1 and patients with normal karyotypes or other cytogenetic changes (P = 0.054). Conclusions Chromosomal abnormalities may provide important prognostic factors for AML in children and be helpful for risk stratification and individual treatment.


2021 ◽  
Vol 58 (2) ◽  
pp. 4988-4995
Author(s):  
N.A.Nuraliyev, A.Kh.Allanazarov, M.S.Gildiyeva, D.R.Sobirova

The aim was to study cytogenetic changes in bone marrow cells of laboratory animals that received and did not receive a genetically modified (GM) product (GM-soy) in a comparative aspect. It was found that in the group of white outbred rats that received GM-soy, cytogenetic changes were found in the cells of the red bone marrow, expressed in partial inhibition of cell proliferation due to the cytotoxic effect. They also had polyploidy (5.35%) and aneuploidy (5.35%) in 10.7% of cases. In addition, this group contained cells with mitotic pathology - chromosome scattering, chromosome pulverization, impaired spiralization and despiralization of chromosomes, premature spiralization of chromosomes, delayed mitosis at the prophase stage. In the group of animals that did not receive soy with and without GM in the cells, there were metaphase plates with a normal karyotype. The mitotic activity of bone marrow cells in the control group was higher (MI - 9%) than in the first (MI - 3%) and the second group (MI - 5%).  


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