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1.
Georgian Med News ; (316-317): 119-123, 2021.
Artigo em Russo | MEDLINE | ID: mdl-34511457

RESUMO

There are data about 6 cases of acute leukemia in children who have been diagnosed with COVID-19 infection 1-1,5 months before, or at the same time. In 5 patients lymphoblastic and in one monoblastic acute leukemia were diagnosed. The course of leukemia passed without any particular complications. Attention is drawn to the presence in 5 patients of either a clone with high hyperdiploidy, or the presence of an increased number of polyploid cells. At the same time, pulverization and fragmentation of chromosomes often observed during radiation, viral exposure, cancer and precancerous hyperplasia, were found. It is suggested that the mitosis disorder we identified in several cases of COVID-19, accompanied by polyploidy, pulverization and fragmentation of chromosomes, can be regarded as a "second hit " during development of childhood acute leukemia, or as an accelerator of the manifestation of an already existing process.


Assuntos
COVID-19 , Leucemia-Linfoma Linfoblástico de Células Precursoras , Criança , Aberrações Cromossômicas , Humanos , Cariotipagem , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , SARS-CoV-2
2.
Rinsho Ketsueki ; 62(8): 1308-1318, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34497221

RESUMO

Leukemias diagnosed in <1-year-old infants generally have an aggressive clinical nature and unique biological characteristics. Acute lymphoblastic leukemia (ALL) in infants is still intractable and difficult to treat as compared with other pediatric ALLs, for which considerable progress in treatment outcomes has been recently achieved. Infant leukemia cells frequently carry chromosome translocations involving the 11q23 locus, resulting in the rearrangement and fusion of the KMT2A (MLL) gene. Among several KMT2A fusion genes, KMT2A-AFF1 (MLL-AF4) fusion is characteristically observed in neonatal and infant ALL, representing a hallmark of poor prognosis. The cytogenetic/molecular abnormalities t (1;22)(p13.3;q13.1)/RBM15-MKL1 and t (8;16)(p11.2;p13.3)/KAT6A-CREBBP (MOZ-CBP) are also well-known in acute myeloblastic leukemia in this population. Although many neonatal leukemias occurring within the first 28 days of birth are refractory, spontaneous remissions are occasionally observed, especially in the case of t (8;16). Therefore, international collaborative studies are necessary to improve understanding and facilitate the development of better treatment for this rare disease. Thus, this study summarizes the recently reported clinical, cytogenetic, and molecular biology aspects of neonatal and infant leukemias.


Assuntos
Leucemia Mieloide Aguda , Leucemia-Linfoma Linfoblástico de Células Precursoras , Doença Aguda , Aberrações Cromossômicas , Humanos , Lactente , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Proteínas de Fusão Oncogênica/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Translocação Genética
3.
Rinsho Ketsueki ; 62(8): 967-977, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34497237

RESUMO

The etiology and pathogenesis of acute myeloid leukemia (AML) have been elucidated at chromosomal and genetic levels. The classification and prognosis for its treatment has clearly involved specific chromosomal aberrations and genetic mutations. The recent comprehensive genomic analysis represented by next-generation sequencers has led to discovering new genetic mutations in AML. These findings have not only been applied clinically as prognostic factors and MRD markers but also contributed to the development of new molecular-targeting drugs. Many new drugs have already been approved in the USA and Europe, and new stratified treatments have tried to incorporate them. With the advent of venetoclax, treatment strategies, especially for patients with poor prognosis and who are unfit, have been substantially revised, and the maintenance therapy for AML is also being reevaluated in accordance to the National Comprehensive Cancer Network guidelines. This article will review the current status of AML treatment in Japan and according to Western guidelines.


Assuntos
Leucemia Mieloide Aguda , Aberrações Cromossômicas , Genômica , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Mutação , Prognóstico
4.
Indian J Med Res ; 153(4): 475-483, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34380794

RESUMO

Background & objectives: B-cell chronic lymphocytic leukaemia (B-CLL) is one of the most common forms of adult leukaemia, with a highly variable clinical course. Specific chromosomal and genetic aberrations are used clinically to predict prognosis, independent from conventional clinical markers. Molecular cytogenetic methods such as fluorescence in situ hybridization (FISH) detect aberrations in up to 80 per cent B-CLL patients. This study was conducted to score the frequencies of recurrent aberrations, i.e., del(13q14), trisomy 12, del(11q22), del(17p13), del(6q21) and IgH (immunoglobulin heavy chain) translocations and to understand their role in prognostication and risk stratification. Methods: FISH studies were performed on bone marrow aspirate or peripheral blood of 280 patients using commercially available disease-specific probe set. The data were correlated with clinical and haematological parameters such as low haemoglobin, splenomegaly and lymphadenopathy. Results: Chromosomal aberrations were detected in 79 per cent of patients, with del(13q14) (57%) as the most common cytogenetic aberration, followed by trisomy 12 (27%), del(11q22) (22%), t(14q32) (19%), del(17p13) (18%) and del(6q21) (9%). Single or in coexistence with other aberration del(13q14) had a favourable outcome in comparison to del(11q22), t(14q32), del(17p13) and del(6q21) which were associated with advanced stages of the disease. Trisomy 12 had a variable clinical course. Interpretation & conclusions: FISH was found to be a sensitive and efficient technique in detecting the prevalence of recurrent cytogenetic abnormalities. Each of these aberrations is an important independent predictor of disease progression and survival which aids in designing risk-adapted treatment strategies for better disease management.


Assuntos
Leucemia Linfocítica Crônica de Células B , Aberrações Cromossômicas , Análise Citogenética , Humanos , Hibridização in Situ Fluorescente , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/genética , Prognóstico
5.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(8): 795-797, 2021 Aug 10.
Artigo em Chinês | MEDLINE | ID: mdl-34365628

RESUMO

OBJECTIVE: To investigate the association of fetal cardiac structural abnormalities with chromosomal aneuploidies and copy number variations (CNVs) in amniocytes. METHODS: 328 pregnant women were subjected to fetal ultrasonography and chromosomal microarray analysis (CMA). Based on the fetal heart structure, the subjects were divided into normal (n=273) and abnormal groups (n=55). The detection rates of chromosomal aneuploidies and CNVs were compared between the two groups. Spearman method was used to assess the association between the results and fetal cardiac structural abnormalities. RESULTS: The detection rates for chromosomal aneuploidies and CNVs in the abnormal group were significantly higher than that in the normal group (P< 0.05), and the incidence of fetal cardiac structural abnormalities was strongly associated with chromosomal aneuploidies and CNVs (P< 0.05). CONCLUSION: Fetal chromosomal aneuploidies and CNVs are strongly associated with cardiac structural abnormalities.


Assuntos
Aneuploidia , Variações do Número de Cópias de DNA , Aberrações Cromossômicas , Feminino , Feto , Humanos , Análise em Microsséries , Gravidez , Diagnóstico Pré-Natal , Ultrassonografia Pré-Natal
6.
Am J Hum Genet ; 108(8): 1409-1422, 2021 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-34237280

RESUMO

Chromosomal aberrations including structural variations (SVs) are a major cause of human genetic diseases. Their detection in clinical routine still relies on standard cytogenetics. Drawbacks of these tests are a very low resolution (karyotyping) and the inability to detect balanced SVs or indicate the genomic localization and orientation of duplicated segments or insertions (copy number variant [CNV] microarrays). Here, we investigated the ability of optical genome mapping (OGM) to detect known constitutional chromosomal aberrations. Ultra-high-molecular-weight DNA was isolated from 85 blood or cultured cells and processed via OGM. A de novo genome assembly was performed followed by structural variant and CNV calling and annotation, and results were compared to known aberrations from standard-of-care tests (karyotype, FISH, and/or CNV microarray). In total, we analyzed 99 chromosomal aberrations, including seven aneuploidies, 19 deletions, 20 duplications, 34 translocations, six inversions, two insertions, six isochromosomes, one ring chromosome, and four complex rearrangements. Several of these variants encompass complex regions of the human genome involved in repeat-mediated microdeletion/microduplication syndromes. High-resolution OGM reached 100% concordance compared to standard assays for all aberrations with non-centromeric breakpoints. This proof-of-principle study demonstrates the ability of OGM to detect nearly all types of chromosomal aberrations. We also suggest suited filtering strategies to prioritize clinically relevant aberrations and discuss future improvements. These results highlight the potential for OGM to provide a cost-effective and easy-to-use alternative that would allow comprehensive detection of chromosomal aberrations and structural variants, which could give rise to an era of "next-generation cytogenetics."


Assuntos
Aberrações Cromossômicas , Transtornos Cromossômicos/diagnóstico , Mapeamento Cromossômico/métodos , Análise Citogenética/métodos , Variações do Número de Cópias de DNA , Genoma Humano , Análise em Microsséries/métodos , Transtornos Cromossômicos/genética , Humanos , Cariotipagem
7.
Am J Hum Genet ; 108(8): 1423-1435, 2021 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-34237281

RESUMO

Somatic structural variants (SVs) are important drivers of cancer development and progression. In a diagnostic set-up, especially for hematological malignancies, the comprehensive analysis of all SVs in a given sample still requires a combination of cytogenetic techniques, including karyotyping, FISH, and CNV microarrays. We hypothesize that the combination of these classical approaches could be replaced by optical genome mapping (OGM). Samples from 52 individuals with a clinical diagnosis of a hematological malignancy, divided into simple (<5 aberrations, n = 36) and complex (≥5 aberrations, n = 16) cases, were processed for OGM, reaching on average: 283-fold genome coverage. OGM called a total of 918 high-confidence SVs per sample, of which, on average, 13 were rare and >100 kb. In addition, on average, 73 CNVs were called per sample, of which six were >5 Mb. For the 36 simple cases, all clinically reported aberrations were detected, including deletions, insertions, inversions, aneuploidies, and translocations. For the 16 complex cases, results were largely concordant between standard-of-care and OGM, but OGM often revealed higher complexity than previously recognized. Detailed technical comparison with standard-of-care tests showed high analytical validity of OGM, resulting in a sensitivity of 100% and a positive predictive value of >80%. Importantly, OGM resulted in a more complete assessment than any previous single test and most likely reported the most accurate underlying genomic architecture (e.g., for complex translocations, chromoanagenesis, and marker chromosomes). In conclusion, the excellent concordance of OGM with diagnostic standard assays demonstrates its potential to replace classical cytogenetic tests as well as to rapidly map novel leukemia drivers.


Assuntos
Aberrações Cromossômicas , Mapeamento Cromossômico/métodos , Análise Citogenética/métodos , Variações do Número de Cópias de DNA , Genoma Humano , Neoplasias Hematológicas/diagnóstico , Análise em Microsséries/métodos , Neoplasias Hematológicas/genética , Humanos , Cariotipagem
8.
Am J Hum Genet ; 108(8): 1436-1449, 2021 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-34216551

RESUMO

Despite widespread clinical genetic testing, many individuals with suspected genetic conditions lack a precise diagnosis, limiting their opportunity to take advantage of state-of-the-art treatments. In some cases, testing reveals difficult-to-evaluate structural differences, candidate variants that do not fully explain the phenotype, single pathogenic variants in recessive disorders, or no variants in genes of interest. Thus, there is a need for better tools to identify a precise genetic diagnosis in individuals when conventional testing approaches have been exhausted. We performed targeted long-read sequencing (T-LRS) using adaptive sampling on the Oxford Nanopore platform on 40 individuals, 10 of whom lacked a complete molecular diagnosis. We computationally targeted up to 151 Mbp of sequence per individual and searched for pathogenic substitutions, structural variants, and methylation differences using a single data source. We detected all genomic aberrations-including single-nucleotide variants, copy number changes, repeat expansions, and methylation differences-identified by prior clinical testing. In 8/8 individuals with complex structural rearrangements, T-LRS enabled more precise resolution of the mutation, leading to changes in clinical management in one case. In ten individuals with suspected Mendelian conditions lacking a precise genetic diagnosis, T-LRS identified pathogenic or likely pathogenic variants in six and variants of uncertain significance in two others. T-LRS accurately identifies pathogenic structural variants, resolves complex rearrangements, and identifies Mendelian variants not detected by other technologies. T-LRS represents an efficient and cost-effective strategy to evaluate high-priority genes and regions or complex clinical testing results.


Assuntos
Aberrações Cromossômicas , Análise Citogenética/métodos , Doenças Genéticas Inatas/diagnóstico , Doenças Genéticas Inatas/genética , Predisposição Genética para Doença , Genoma Humano , Mutação , Variações do Número de Cópias de DNA , Feminino , Testes Genéticos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Cariotipagem , Masculino , Análise de Sequência de DNA
9.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(7): 690-693, 2021 Jul 10.
Artigo em Chinês | MEDLINE | ID: mdl-34247380

RESUMO

OBJECTIVE: To explore the phenotypic and genetic characteristics of acute megakaryoblastic leukemia (AMKL) in young children accompany by WT1, MLL-PTD and EVI1, in order to improve the diagnosis level of AMKL. METHODS: EDTA-K2 anticoagulation venous blood was collected for blood routine and morphological analysis of blood cells; bone marrow was extracted for cell morphology, immunophenotype, chromosome karyotype and fusion gene analysis. RESULTS: White blood cell count was 12.3× 109/L, hemoglobin was 73 g/L, and platelet count was 13× 109/L. The morphological analysis of blood cells showed that the size of immature cells was like that of primitive immature lymphocytes, which was circular or irregular and part of them with obvious pseudopodia. The cytoplasm is basophilic with heterogeneous coloration and granules. Nuclear chromatin is fine and even, 1-3 nucleoli can be seen, these immature cells account for about 40%; the morphology of bone marrow cells was consistent with acute leukemia, negative for peroxidase staining, negative for AS-DNCE staining and alpha-NBE staining. Flow cytometry results showed that the protocells account for about 52% and significant expression of megakaryocytes related markers (cCD41+, CD61+, CD36+). Chromosome karyotype is 46, XX, der(3) add(3)(p21)add(3)(q25), add (9)(q22), -13, +mar [4]/46, XX, del(13)(q12q22) [3]/46, XX[3]. The fusion gene WT1 was overexpressed, MLL-PTD and EVI1 were positive. CONCLUSION: Acute megakaryocytic leukemia has unique and complex phenotypic and genetics characteristics.


Assuntos
Leucemia Megacarioblástica Aguda , Medula Óssea , Criança , Pré-Escolar , Aberrações Cromossômicas , Humanos , Cariotipagem , Leucemia Megacarioblástica Aguda/genética , Proteína do Locus do Complexo MDS1 e EVI1 , Megacariócitos , Proteínas de Fusão Oncogênica , Proteínas WT1
10.
Int J Mol Sci ; 22(14)2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34299125

RESUMO

Medical staff represent the largest group of workers occupationally exposed to ionizing radiation (IR). Chronic exposure to low-dose IR may result in DNA damage and genotoxicity associated with increased risk of cancer. This review aims to identify the genotoxicity biomarkers that are the most elevated in IR-exposed vs. unexposed health workers. A systematic review of the literature was performed to retrieve relevant studies with various biomarkers of genotoxicity. Subsequent meta-analyses produced a pooled effect size for several endpoints. The search procedure yielded 65 studies. Chromosome aberrations (CA) and micronuclei (MN) frequencies were significantly different between IR-exposed and unexposed workers (θpooled = 3.19, 95% CI 1.46-4.93; and θpooled = 1.41, 95% CI 0.97-1.86, for total aberrant cells and MN frequencies, respectively), which was not the case for ring chromosomes and nucleoplasmic bridges. Although less frequently used, stable translocations, sister chromatid exchanges (SCE) and comet assay endpoints were also statistically different between IR-exposed and unexposed workers. This review confirms the relevance of CA and MN as genotoxicity biomarkers that are consistently elevated in IR-exposed vs. unexposed workers. Other endpoints are strong candidates but require further studies to validate their usefulness. The integration of the identified biomarkers in future prospective epidemiological studies is encouraged.


Assuntos
Biomarcadores/análise , Aberrações Cromossômicas/efeitos da radiação , Dano ao DNA , Pessoal de Saúde/estatística & dados numéricos , Exposição Ocupacional/análise , Radiação Ionizante , Relação Dose-Resposta à Radiação , Humanos , Exposição Ocupacional/efeitos adversos
11.
Environ Monit Assess ; 193(8): 526, 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34322773

RESUMO

Industrial effluents contain hazardous substances that can be a serious threat to the agriculture and human health. In the present study, the cytotoxic and genotoxic impacts of agricultural soil from the industrial area of Dera Bassi (Punjab, India) have been evaluated. Assays such as defects in DNA repair in K-12 mutants of Escherichia coli and chromosomal aberrations in Allium cepa were used to estimate the acute toxicity and chromosomal mutagenesis, respectively. Atomic absorption spectrometry and GC-MS analysis revealed contamination of the soil with high concentrations of heavy metals and organic compounds, respectively. Dichloromethane extract of site I soil sample caused maximum damage to 40 µL mL-1 DNA repair defective mutants and showed 38 and 49% survival in lexA and recA mutants, respectively, which was least among all the sites. In A. cepa test, an inverse relationship between soil extract concentration and the mitotic index was observed. Exposure of growing roots of A. cepa to soil extracts induced chromosomal abnormalities and alterations in mitotic phases in root tip cells. The study concludes that agricultural sites near the industrial area were contaminated with genotoxic and mutagenic compounds. Hence, adequate measures should be taken to reduce the toxicity of industrial effluents discharged onto the agricultural fields.


Assuntos
Monitoramento Ambiental , Solo , Agricultura , Aberrações Cromossômicas , Dano ao DNA , Humanos , Índia , Cebolas/genética , Raízes de Plantas
12.
Epidemiol Prev ; 45(3): 196-204, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34212701

RESUMO

OBJECTIVES: to assess the potential of a new algorithm based on current healthcare databases to identify potential cases of malformation, particularly chromosomal anomalies associated with terminations of pregnancy. DESIGN: retrospective observational study. SETTING AND PARTICIPANTS: Registry of Congenital Anomalies of Milan, live births, still births, and termination of pregnancies for fetal anomalies from 2012 to 2016, detected by using current healthcare data. MAIN OUTCOME MEASURES: prevalence between 2012 and 2016 of congenital malformations recorded by Milan's Registry of Congenital Anomalies, with particular regard to chromosomal anomaly trends. Variation in the percentage of malformations detected from terminations of pregnancy. RESULTS: prevalence of malformations increased from 270 in 2012 to 283 per 10,000 in 2016; specifically, chromosomal abnormalities increased from 35 to 51 per 10,000 births. The algorithm detected a greater proportion of anomalies associated with therapeutic abortion, especially with respect to chromosomal anomalies, with an increase from 57.7% in 2012 to 75.8% in 2016 (test for trend p=0.002). CONCLUSIONS: the proposed algorithm identified a greater number of chromosomal anomalies that caused termination of pregnancy and may be applied to existing Italian registries to evaluate the quality of healthcare services, in particular with regard to the effectiveness of prenatal trisomy screening policies. The algorithm may also be used where no active surveillance systems are present, as well as in epidemiological studies, to assess environmental impact on congenital anomalies.


Assuntos
Algoritmos , Aberrações Cromossômicas , Anormalidades Congênitas , Diagnóstico Pré-Natal , Anormalidades Congênitas/diagnóstico , Anormalidades Congênitas/epidemiologia , Feminino , Humanos , Itália/epidemiologia , Gravidez , Prevalência , Sistema de Registros , Reprodutibilidade dos Testes , Estudos Retrospectivos
13.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(7): 694-698, 2021 Jul 10.
Artigo em Chinês | MEDLINE | ID: mdl-34247381

RESUMO

As a prenatal testing for chromosomal abnormalities, non-invasive prenatal testing (NIPT) has been integrated into prenatal healthcare service. NIPT has shown a high sensitivity and specificity for screening fetal trisomies 13, 18 and 21, and has attained excellent clinical results. With the propagation of the NIPT screening, international organizations have issued guidelines and comments for its clinical utility with regular updating. China has also developed guidelines for NIPT in 2016. NIPT guidelines in various countries have provided valuable guidance for its target diseases and suitable patient groups, but there has been few research data on its clinical application for special groups of patients. Based on the guidelines and comments of various professional bodies and published data on the clinical utility of NIPT, in addition with consideration of the conditions in China, clinical utility of NIPT for particular groups of pregnant women, including those with advanced maternal age, obesity, twin pregnancy and fetal ultrasonographic anomalies, are reviewed. The value of genetic counseling for NIPT is also emphasized, which is critical for the clinical application of NIPT.


Assuntos
Gestantes , Diagnóstico Pré-Natal , China , Aberrações Cromossômicas , Feminino , Humanos , Gravidez , Síndrome da Trissomia do Cromossomo 13
14.
Georgian Med News ; (314): 139-145, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34248044

RESUMO

Objective - to study the ability of 2,6-dimethylpyridine-N-oxide to modify the cytogenetic effects in mouse bone marrow cells caused by the pro-oxidant mutagen Dioxidine. The cytogenetic activity and mutagen-modifying effect of the plant growth regulator 2,6-dimethylpyridine-N-oxide (Ivin) were studied by the method of accounting for chromosomal aberrations in the bone marrow cells of CD-1 mice (males) with a single joint exposure with Dioxidine. Ivin was administered single orally in the form of an aqueous solution at doses of 710, 71, and 0.7 mg/kg bw, which corresponds to 1/2, 1/20, 1/2000 of LD50 after intraperitoneally administered of Dioxidine at a dose 100 mg/kg. The animals of the positive control group were treated Dioxidine intraperitoneally at a dose of 100 mg/kg bw. Intact animals (negative control group) were orally administered purified, UV-sterilized, deionized water. It was shown that when combined with Dioxidine, Ivin at doses of 710, 71, and 0,7 mg/kg bw significally reduced the frequency of metaphases chromosome aberrations, relative to positive control by 55,56%, 66,70%, and 74,08% respectively. No multi-aberrant and polyploid cells were observed. In all variants of the experiment, only chromatid-type chromosome aberrations with single fragments were detected in the spectrum of chromosome aberrations. The severity of this effect had an inverse dose dependence: with a decrease in the dose of Ivin, the cytogenetic effects of Dioxidine decreased to a greater extent than with high doses of Ivin. The high antimutagenic effect of Ivin was confirmed, which is expressed to a greater extent when it is combined with Dioxidine than with Cyclophosphamide. These findings may be associated with the genoprotective effect of Ivin, due to the stabilization of membranes and its antioxidant effect.


Assuntos
Aberrações Cromossômicas , Óxidos , Animais , Células da Medula Óssea , Análise Citogenética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Quinoxalinas
15.
Gan To Kagaku Ryoho ; 48(7): 971-974, 2021 Jul.
Artigo em Japonês | MEDLINE | ID: mdl-34267039

RESUMO

The patient developed Stage Ⅳ transverse colon cancer at the age of 72 years and was treated with an 8-course XELOX regimen(capecitabine and oxaliplatin)every 3 weeks after resection. Six years and 9 months after the end of treatment, at the age of 79 years, WBC levels were found to have markedly increased to 10×104/µL in the patient, and acute leukemia was suspected; subsequently, the patient was hospitalized. Bone marrow was aspirated and analyzed, and the results showed that 95% of leukemic cells were positive for esterase staining. Chromosomal examination revealed t(6 ; 11)(q27 ; q23), ie, the diagnosis of therapy-related acute myeloid leukemia(t-AML)with 11q23 abnormality. CR was achieved by chemotherapy, but the disease soon recurred; the patient died 7 months after the onset of t-AML, with the cause being t- AML with 11q23 abnormality that developed 6 years and 9 months after treatment for colorectal cancer with oxaliplatin and capecitabine without undergoing MDS. Since there is a possibility of leukemia induction following oxaliplatin treatment, more such cases need to be monitored in the future.


Assuntos
Neoplasias Colorretais , Leucemia Mieloide Aguda , Idoso , Aberrações Cromossômicas , Neoplasias Colorretais/tratamento farmacológico , Histona-Lisina N-Metiltransferase , Humanos , Leucemia Mieloide Aguda/induzido quimicamente , Leucemia Mieloide Aguda/tratamento farmacológico , Proteína de Leucina Linfoide-Mieloide/genética
16.
Radiol Med ; 126(9): 1226-1235, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34159496

RESUMO

OBJECTIVES: We aimed to investigate the feasibility of predicting high-risk cytogenetic abnormalities (HRCAs) in patients with multiple myeloma (MM) using a spinal MRI-based radiomics method. MATERIALS AND METHODS: In this retrospective study, we analyzed the radiomic features of 248 lesions (HRCA [n = 111] and non-HRCA [n = 137]) using T1WI, T2WI, and fat suppression T2WI. To construct the radiomics model, the top nine most frequent radiomic features were selected using logistic regression (LR) machine-learning processes. A combined LR model incorporating radiomic features and basic clinical characteristics (age and sex) was also built. Fivefold external cross-validation was performed, and a comparative analysis of 10 random fivefold cross-validation sets was used to verify result stability. Model performance was compared by plotting receiver operating characteristic curves and the area under the curve (AUC). RESULTS: Comparable AUC values were observed between the radiomics model and the combined model in validation cohorts (AUC: 0.863 vs. 0.870, respectively, p = 0.206). The radiomics model had an AUC of 0.863, with a sensitivity of 0.789, a specificity of 0.787, a positive predictive value of 0.753, a negative predictive value of 0.824, and an accuracy of 0.788 in the validation cohort, which were comparable with the performance in the training cohorts. CONCLUSIONS: Radiomic features of routine spinal MRI reflect differences between HRCAs and non-HRCAs in patients with MM. This MRI-based radiomics model might be a useful and independent tool to predict HRCAs in patients MM.


Assuntos
Aberrações Cromossômicas , Imageamento por Ressonância Magnética , Mieloma Múltiplo/genética , Coluna Vertebral/diagnóstico por imagem , Idoso , Área Sob a Curva , Feminino , Humanos , Modelos Logísticos , Aprendizado de Máquina , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico por imagem , Mieloma Múltiplo/patologia , Valor Preditivo dos Testes , Curva ROC , Estudos Retrospectivos , Coluna Vertebral/patologia
17.
Nat Med ; 27(6): 1012-1024, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34099924

RESUMO

Age is the dominant risk factor for infectious diseases, but the mechanisms linking age to infectious disease risk are incompletely understood. Age-related mosaic chromosomal alterations (mCAs) detected from genotyping of blood-derived DNA, are structural somatic variants indicative of clonal hematopoiesis, and are associated with aberrant leukocyte cell counts, hematological malignancy, and mortality. Here, we show that mCAs predispose to diverse types of infections. We analyzed mCAs from 768,762 individuals without hematological cancer at the time of DNA acquisition across five biobanks. Expanded autosomal mCAs were associated with diverse incident infections (hazard ratio (HR) 1.25; 95% confidence interval (CI) = 1.15-1.36; P = 1.8 × 10-7), including sepsis (HR 2.68; 95% CI = 2.25-3.19; P = 3.1 × 10-28), pneumonia (HR 1.76; 95% CI = 1.53-2.03; P = 2.3 × 10-15), digestive system infections (HR 1.51; 95% CI = 1.32-1.73; P = 2.2 × 10-9) and genitourinary infections (HR 1.25; 95% CI = 1.11-1.41; P = 3.7 × 10-4). A genome-wide association study of expanded mCAs identified 63 loci, which were enriched at transcriptional regulatory sites for immune cells. These results suggest that mCAs are a marker of impaired immunity and confer increased predisposition to infections.


Assuntos
Envelhecimento/genética , Doenças Transmissíveis/genética , Pneumonia/genética , Sepse/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/patologia , Bancos de Espécimes Biológicos , Aberrações Cromossômicas , Doenças Transmissíveis/complicações , Doenças Transmissíveis/microbiologia , Doenças do Sistema Digestório/epidemiologia , Doenças do Sistema Digestório/genética , Doenças do Sistema Digestório/microbiologia , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Mosaicismo , Pneumonia/epidemiologia , Pneumonia/microbiologia , Fatores de Risco , Sepse/epidemiologia , Sepse/microbiologia , Anormalidades Urogenitais/epidemiologia , Anormalidades Urogenitais/genética , Anormalidades Urogenitais/microbiologia , Adulto Jovem
18.
Nucleic Acids Res ; 49(12): 6817-6831, 2021 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-34125900

RESUMO

Chromosome fusions threaten genome integrity and promote cancer by engaging catastrophic mutational processes, namely chromosome breakage-fusion-bridge cycles and chromothripsis. Chromosome fusions are frequent in cells incurring telomere dysfunctions or those exposed to DNA breakage. Their occurrence and therefore their contribution to genome instability in unchallenged cells is unknown. To address this issue, we constructed a genetic assay able to capture and quantify rare chromosome fusions in budding yeast. This chromosome fusion capture (CFC) assay relies on the controlled inactivation of one centromere to rescue unstable dicentric chromosome fusions. It is sensitive enough to quantify the basal rate of end-to-end chromosome fusions occurring in wild-type cells. These fusions depend on canonical nonhomologous end joining (NHEJ). Our results show that chromosome end protection results from a trade-off at telomeres between positive effectors (Rif2, Sir4, telomerase) and a negative effector partially antagonizing them (Rif1). The CFC assay also captures NHEJ-dependent chromosome fusions induced by ionizing radiation. It provides evidence for chromosomal rearrangements stemming from a single photon-matter interaction.


Assuntos
Aberrações Cromossômicas , Reparo do DNA por Junção de Extremidades/efeitos da radiação , Telômero , Centrômero , Técnicas Genéticas , Radiação Ionizante , Saccharomyces cerevisiae/genética , Telômero/metabolismo , Homeostase do Telômero
19.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(6): 573-576, 2021 Jun 10.
Artigo em Chinês | MEDLINE | ID: mdl-34096029

RESUMO

OBJECTIVE: To determine the chromosomal karyotype of a fetus with copy number variation (CNV) of the X chromosome signaled by non-invasive prenatal testing (NIPT). METHODS: NIPT was performed on the peripheral blood sample taken from the pregnant women. Amniotic fluid and cord blood samples were subjected to conventional G banded karyotyping, and were further analyzed by high-throughput sequencing for chromosome microdeletion/microduplication. The results were then verified by fluorescence in situ hybridization (FISH) on metaphase cells. RESULTS: The NIPT test of pregnant women suggested low risk for 21-trisomy, 18-trisomy, and 13-trisomy, whilst indicated the number of chromosome X to be low. The G banded karyotype of the amniotic fluid and cord blood cells was 46,XX. The result of high-throughput sequencing chromosome microdeletion/microduplication detection was seq[hg19](X)× 1, (Y)× 2. FISH showed a clear red signal at each end of a whole chromosome, and a green signal on the other chromosome, with a karyotype of 46,X,ish idic(Y) (q11.23) (SRY++, DXZ1+). C banding showed that there is a dense and a slightly loose centromere at both ends of the Y chromosome, and the parachromatin region was missing. The karyotype of amniotic fluid and cord blood cells was finally determined to be 46,X, pus idic(Y) (q11.23). CONCLUSION: For chromosome anomalies suggested by auxiliary report of NIPT, conventional karyotyping combined with high-throughput sequencing for chromosome microdeletion/microduplication should be adopted for the prevention and reduction of the rate of chromosome microdeletion/microduplication syndromes.


Assuntos
Variações do Número de Cópias de DNA , Diagnóstico Pré-Natal , Aberrações Cromossômicas , Feminino , Humanos , Hibridização in Situ Fluorescente , Gravidez , Cromossomo X
20.
Zhonghua Bing Li Xue Za Zhi ; 50(6): 604-608, 2021 Jun 08.
Artigo em Chinês | MEDLINE | ID: mdl-34078047

RESUMO

Objective: To investigate the clinicopathological features, molecular genetics, treatment and prognosis of Burkitt-like lymphoma with 11q aberration (BLL-11q). Methods: Six cases of BLL-11q diagnosed at the First Affiliated Hospital of Zhengzhou University, from January 2016 to January 2020 were reviewed and analyzed using hematoxylin-eosin staining, immunohistochemistry, EBER in situ hybridization and fluorescence in situ hybridization. Clinical information including follow-up data was collected and analyzed. Results: The median age of the six immunocompetent patients was 29 years (range 20-38 years) and the male to female ratio was 5∶1. All patients had nodal disease in the head and neck region. Five patients had Ann Arbor stage Ⅰ-Ⅱ disease, while one patient had stage Ⅳ disease. Lymph nodes showed partial or total architectural effacement by a diffuse proliferation of monomorphic lymphocytes. Four cases were morphologically similar to Burkitt lymphoma, and two cases were unclassified with histological features between Burkitt lymphoma and diffuse large B-cell lymphoma. Mitotic figures, apoptosis and necrosis were conspicuous. Five cases exhibited the"starry sky"pattern. CD20, CD10 and bcl-6 were diffusely and strongly positive. The Ki-67 index was more than 95%. The follicular-dendritic-cell meshwork was noted in one case using CD21 stain. C-MYC was expressed variably. CD3, bcl-2, MUM-1, CD30 and TDT were negative in all cases. EBER in situ hybridization was also all negative. FISH analyses using C-MYC, bcl-2 and bcl-6 break-apart probes were all negative. All cases had the 11q23.3 gain/11q24.3 loss pattern, and 11q23.3 amplification was found in one case. IgH and IRF4 break-apart probes analysis was also negative. All patients were alive with no disease after a follow-up of 4 to 19 months. Conclusion: BLL-11q is a rare lymphoma that resembles Burkitt lymphoma morphologically and phenotypically, but lacks C-MYC gene rearrangements. Instead, it has a chromosome-11q alteration characterized by proximal gains and telomeric losses. It's necessary to improve our understanding of BLL-11q to avoid misdiagnosis and missed diagnosis.


Assuntos
Linfoma de Burkitt , Linfoma Difuso de Grandes Células B , Adulto , Linfoma de Burkitt/genética , Aberrações Cromossômicas , Feminino , Genes myc/genética , Humanos , Hibridização in Situ Fluorescente , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , Masculino , Biologia Molecular , Translocação Genética , Adulto Jovem
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