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1.
J Obstet Gynaecol ; 44(1): 2348085, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38708796

ABSTRACT

BACKGROUND: Primary amenorrhoea (PA) refers to an ailment when adolescent girls do not attain menarche naturally. It is one of the most common gynaecological disorders specified. Chromosomal abnormalities play a pivotal role in PA. Cytogenetic analysis is an indispensable diagnostic tool to determine the abnormality of the chromosome. In an emerging country like India, cytogenetic analysis is at a nascent stage. There are very few studies on Cytogenetics present in eastern India, including West Bengal. In rural and suburban areas PA sufferers often experience late diagnosis and struggle to access suitable curative management. The aim of the study is to evaluate the various types of chromosomal abnormalities in patients suffering from PA for accurate, better management of the same and further counselling. METHODS: A total of 40 PA cases were referred by obstetricians and gynaecologists to the Department of Genetics of Nirnayan Health Care, Kolkata. To screen the chromosomal abnormalities, human leukocyte culture was accomplished with their peripheral venous blood followed by G-banding and then karyotyping was executed according to ISCN-2020. RESULT: Out of 40 patients, 29 were normal among which 46,XX was found in 70% cases (n = 28) and 46,XX,9qh + in 2.5% (n = 1). The remaining 11 showed different types of abnormalities. 45,X was found in 10% (n = 4), 46,X,i(X)(q10) in 2.5% (n = 1), 46,X,del(X)(p11.2) in 2.5% (n = 1), 46,X,del(X)(p22.1) in 2.5% (n = 1), 46,X,del(X)(q24) in 2.5% (n = 1), 46,XY in 2.5% (n = 1), mos 45,X[22]/46,Xi(X)(q.10)[8] in 2.5% (n = 1) and mos 45,X[16]/46,XY[14] (2.5%) in 2.5% (n = 1). CONCLUSION: This study indicates the importance of chromosomal study which must be included in early diagnosis of PA. Karyotyping at the appropriate phase of life will not only help in the judicial management of this disorder but will also give young girls a better lifestyle.


Primary amenorrhoea is a common gynecological disorder reported in adolescent girls, often linked to chromosomal abnormalities. In Eastern India, including West Bengal, where cytogenetic analysis is still in its nascent stage, late diagnosis and limited access to curative management are prevalent issues. A study conducted from January 2021 to May 2023 at Nirnayan Healthcare, Kolkata aimed to evaluate chromosomal abnormalities in 40 PA cases. Out of these, 28 exhibited normal karyotypes (46,XX); one patient was reported with 46,XX,9qh + which is considered a normal karyotype, while the remaining 11 revealed diverse abnormalities, including 45,X; sex reversal & several structural variations. The study underscores the significance of cytogenetic analysis in the early diagnosis of Primary Amenorrhoea. Early karyotyping not only facilitates judicious management but also ensures a better lifestyle for affected girls.


Subject(s)
Amenorrhea , Chromosome Aberrations , Cytogenetic Analysis , Karyotyping , Humans , Female , India , Amenorrhea/genetics , Adolescent , Adult , Chromosome Aberrations/statistics & numerical data , Young Adult
2.
Gac Med Mex ; 160(1): 76-85, 2024.
Article in English | MEDLINE | ID: mdl-38753554

ABSTRACT

BACKGROUND: Chromosomal abnormalities are present in 50 to 60% of miscarriages and in 6 to 19% of stillbirths. Although microarrays are preferred for studying chromosomal abnormalities, many hospitals cannot offer this methodology. OBJECTIVE: To present the results of the cytogenetic analysis of 303 products of conception (POC), which included 184 miscarriages, 49 stillbirths and 17 cases of undefined age. MATERIAL AND METHODS: Karyotyping, fluorescence in situ hybridization, short tandem repeats and microarrays were used, depending on the type of loss and available sample. RESULTS: In 29 POCs we found maternal tissue and were eliminated from the analyses. Informative results were obtained in 250 (91.2 %)/274 cases; the karyotyping success rate was 80.7%; that of single nucleotide polymorphism microarrays, 94.5%; and that of fluorescence in situ hybridization and short tandem repeat, 100%. Cytogenetic abnormalities were observed in 57.6% of miscarriages and in 24.5% of stillbirths; 94% of total anomalies were numerical and 6% were submicroscopic. CONCLUSIONS: Karyotyping with simultaneous short tandem repeat study to rule out contamination of maternal cells is effective for studying miscarriages; in stillbirths, microarrays are recommended.


ANTECEDENTES: Las alteraciones cromosómicas están presentes en 50 a 60 % de los abortos espontáneos y en 6 a 19 % de los mortinatos. Aunque se prefieren los microarreglos para estudiarlos, numerosos hospitales no pueden ofrecerlos. OBJETIVO: Presentar los resultados del estudio citogenético de 303 productos de la concepción (POC), 184 se obtuvieron de abortos espontáneos, 49 fueron mortinatos y en 17 no se identificó la de edad gestacional. MATERIAL Y MÉTODOS: Se empleó cariotipo, hibridación in situ con fluorescencia, secuencias cortas repetidas en tándem y microarreglos, según el tipo de pérdida y la muestra disponible. RESULTADOS: En 29 POC se encontró tejido materno, por lo que fueron eliminados de los análisis. En 250 (91.2 %)/274 casos se obtuvieron resultados informativos; la tasa de éxito del cariotipo fue de 80.7 %; la de los microarreglos de SNP, de 94.5 %; y la de la hibridación fluorescente in situ y la repetición corta en tándem, de 100 %. Se observaron anomalías citogenéticas en 57.6 % de los abortos espontáneos y en 24.5 % de los mortinatos; 94 % de las anomalías fueron numéricas y 6 %, submicroscópicas. CONCLUSIONES: El cariotipo en conjunto con el estudio de secuencias cortas repetidas en tándem para descartar contaminación de células maternas es efectivo para estudiar abortos espontáneos; los microarreglos se recomiendan en los mortinatos.


Subject(s)
Abortion, Spontaneous , Chromosome Aberrations , In Situ Hybridization, Fluorescence , Karyotyping , Humans , Female , Abortion, Spontaneous/epidemiology , Abortion, Spontaneous/genetics , Mexico/epidemiology , Pregnancy , Karyotyping/methods , Stillbirth/genetics , Stillbirth/epidemiology , Adult , Cytogenetic Analysis/methods , Microsatellite Repeats , Polymorphism, Single Nucleotide , Young Adult
3.
Genes (Basel) ; 15(5)2024 Apr 27.
Article in English | MEDLINE | ID: mdl-38790188

ABSTRACT

Cytogenetic studies are essential in the diagnosis and follow up of patients with bone marrow failure syndromes (BMFSs), but obtaining good quality results is often challenging due to hypocellularity. Optical Genome Mapping (OGM), a novel technology capable of detecting most types chromosomal structural variants (SVs) at high resolution, is being increasingly used in many settings, including hematologic malignancies. Herein, we compared conventional cytogenetic techniques to OGM in 20 patients with diverse BMFSs. Twenty metaphases for the karyotype were only obtained in three subjects (15%), and no SVs were found in any of the samples. One patient with culture failure showed a gain in chromosome 1q by fluorescence in situ hybridization, which was confirmed by OGM. In contrast, OGM provided good quality results in all subjects, and SVs were detected in 14 of them (70%), mostly corresponding to cryptic submicroscopic alterations not observed by standard techniques. Therefore, OGM emerges as a powerful tool that provides complete and evaluable results in hypocellular BMFSs, reducing multiple tests into a single assay and overcoming some of the main limitations of conventional techniques. Furthermore, in addition to confirming the abnormalities detected by conventional techniques, OGM found new alterations beyond their detection limits.


Subject(s)
In Situ Hybridization, Fluorescence , Humans , Male , Female , Middle Aged , Adult , Aged , In Situ Hybridization, Fluorescence/methods , Chromosome Mapping/methods , Bone Marrow Failure Disorders/genetics , Chromosome Aberrations , Adolescent , Cytogenetic Analysis/methods , Bone Marrow Diseases/genetics , Karyotyping/methods , Young Adult
4.
Cancer Med ; 13(8): e7172, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38651186

ABSTRACT

BACKGROUND: Quantitative measurement of minimal residual disease (MRD) is the "gold standard" for estimating the response to therapy in childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Nevertheless, the speed of the MRD response differs for different cytogenetic subgroups. Here we present results of MRD measurement in children with BCP-ALL, in terms of genetic subgroups with relation to clinically defined risk groups. METHODS: A total of 485 children with non-high-risk BCP-ALL with available cytogenetic data and MRD studied at the end-of-induction (EOI) by multicolor flow cytometry (MFC) were included. All patients were treated with standard-risk (SR) of intermediate-risk (ImR) regimens of "ALL-MB 2008" reduced-intensity protocol. RESULTS AND DISCUSSION: Among all study group patients, 203 were found to have low-risk cytogenetics (ETV6::RUNX1 or high hyperdiploidy), while remaining 282 children were classified in intermediate cytogenetic risk group. For the patients with favorable and intermediate risk cytogenetics, the most significant thresholds for MFC-MRD values were different: 0.03% and 0.04% respectively. Nevertheless, the most meaningful thresholds were different for clinically defined SR and ImR groups. For the SR group, irrespective to presence/absence of favorable genetic lesions, MFC-MRD threshold of 0.1% was the most clinically valuable, although for ImR group the most informative thresholds were different in patients from low-(0.03%) and intermediate (0.01%) cytogenetic risk groups. CONCLUSION: Our data show that combining clinical risk factors with MFC-MRD measurement is the most useful tool for risk group stratification of children with BCP-ALL in the reduced-intensity protocols. However, this algorithm can be supplemented with cytogenetic data for part of the ImR group.


Subject(s)
Flow Cytometry , Neoplasm, Residual , Humans , Neoplasm, Residual/genetics , Child , Flow Cytometry/methods , Male , Female , Child, Preschool , Adolescent , Infant , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Cytogenetic Analysis/methods , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/genetics , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/diagnosis , Core Binding Factor Alpha 2 Subunit/genetics
5.
Genes (Basel) ; 15(4)2024 Mar 28.
Article in English | MEDLINE | ID: mdl-38674364

ABSTRACT

Satellite DNA (satDNA) consists of sequences of DNA that form tandem repetitions across the genome, and it is notorious for its diversity and fast evolutionary rate. Despite its importance, satDNA has been only sporadically studied in reptile lineages. Here, we sequenced genomic DNA and PCR-amplified microdissected W chromosomes on the Illumina platform in order to characterize the monomers of satDNA from the Henkel's leaf-tailed gecko U. henkeli and to compare their topology by in situ hybridization in the karyotypes of the closely related Günther's flat-tail gecko U. guentheri and gold dust day gecko P. laticauda. We identified seventeen different satDNAs; twelve of them seem to accumulate in centromeres, telomeres and/or the W chromosome. Notably, centromeric and telomeric regions seem to share similar types of satDNAs, and we found two that seem to accumulate at both edges of all chromosomes in all three species. We speculate that the long-term stability of all-acrocentric karyotypes in geckos might be explained from the presence of specific satDNAs at the centromeric regions that are strong meiotic drivers, a hypothesis that should be further tested.


Subject(s)
Centromere , Cytogenetic Analysis , DNA, Satellite , Karyotype , Lizards , Telomere , Animals , Lizards/genetics , Centromere/genetics , DNA, Satellite/genetics , Telomere/genetics , Cytogenetic Analysis/methods , In Situ Hybridization, Fluorescence
6.
BMC Cancer ; 24(1): 530, 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38664756

ABSTRACT

BACKGROUND: In low-income countries there is insufficient evidence on hematological, clinical, cytogenetic and molecular profiles among new CML patients. Therefore, we performed this study among newly confirmed CML patients at Tikur Anbesa Specialized Hospital (TASH), Ethiopia. OBJECTIVE: To determine the hematological, clinical, cytogenetic and molecular profiles of confirmed CML patients at tertiary care teaching hospital in Addis Ababa, Ethiopia. METHODS: A facility-based cross-sectional study was conducted to evaluate hematological, clinical, cytogenetic and molecular profiles of confirmed CML patients at TASH from August 2021 to December 2022. A structured questionnaire was used to collect the patients' sociodemographic information, medical history and physical examination, and blood samples were also collected for hematological, cytogenetic and molecular tests. Descriptive statistics were used to analyze the sociodemographic, hematological, clinical, cytogenetic and molecular profiles of the study participants. RESULTS: A total of 251 confirmed new CML patients were recruited for the study. The majority of patients were male (151 [60.2%]; chronic (CP) CML, 213 [84.7%]; and had a median age of 36 years. The median (IQR) WBC, RBC, HGB and PLT counts were 217.7 (155.62-307.4) x103/µL, 3.2 (2.72-3.6) x106/µL, 9.3 (8.2-11) g/dl and 324 (211-499) x 103/µL, respectively. All patients had leukocytosis, and 92.8%, 95.6% and 99.2% of the patients developed anemia, hyperleukocytosis and neutrophilia, respectively. Fatigue, abdominal pain, splenomegaly and weight loss were the common signs and symptoms observed among CML patients. Approximately 86.1% of the study participants were Philadelphia chromosome positive (Ph+) according to fluorescence in situ hybridization (FISH). P210, the major breakpoint protein, transcript was detected by both qualitative polymerase chain reaction (PCR) and quantitative real time polymerase chain reaction (PCR). CONCLUSION: During presentation, most CML patients presented with hyperleukocytosis, neutrophilia and anemia at TASH, Addis Ababa. Fatigue, abdominal pain, splenomegaly and weight loss were the most common signs and symptoms observed in the CML patients. Most CML patients were diagnosed by FISH, and p120 was detected in all CML patients diagnosed by PCR. The majority of CML patients arrive at referral center with advanced signs and symptoms, so better to decentralize the service to peripheral health facilities.


Subject(s)
Hospitals, Teaching , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Humans , Male , Cross-Sectional Studies , Female , Ethiopia/epidemiology , Adult , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/blood , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , Middle Aged , Young Adult , Adolescent , Tertiary Care Centers/statistics & numerical data , Aged , Cytogenetic Analysis , Fusion Proteins, bcr-abl/genetics , Tertiary Healthcare
7.
Int J Radiat Biol ; 100(6): 875-889, 2024.
Article in English | MEDLINE | ID: mdl-38647504

ABSTRACT

PURPOSE: To examine the distortion of the linear quadratic (LQ) model of in vitro cytogenetic dose response over an extended range of γ-ray doses by analyzing the available literature data, and to establish the dose ranges, in which the LQ dose response curve (DRC) can be most accurately fitted for biological dosimetry. MATERIALS AND METHODS: Data on yields of dicentrics (Dic) or dicentrics plus centric rings (Dic + CR) induced in vitro in human lymphocytes by acute γ-rays were extracted from 108 open sources. The overall dose response dataset in the dose range up to 50 Gy was fitted to a fractional-rational (FR) model, which included a 'basic' LQ function in the numerator, and a reduction factor dependent on the square of the dose in the denominator. Cytogenetic dose response data obtained at Grigoriev Institute for Medical Radiology, Kharkiv, Ukraine (GIMRO) in the range 0.1 - 20.3 Gy acute γ-rays were fitted to the LQ model with the progressive changing minimum or maximum radiation dose. RESULTS: The overall dose response, as expected, followed the LQ function in the dose range ≤5 Gy, but in the extended dose range appeared to be S-shaped, with intensive saturation and a plateau at doses ≥22 Gy. Coefficients of the 'basic' LQ equation in FR model were very close to many published DRCs; calculated asymptote was 17. Fitting of the GIMRO dataset to the LQ model with the shift of the dose range showed the increase in linear coefficient with the increment of either minimum or maximum radiation dose, while the decline of the quadratic coefficient was regulated mostly by the increase of the highest dose. The best goodness of fit, assessed by lower χ2 values, occurred for dose ranges 0.1 - 1.0 Gy; 0.5 - 5.9 Gy; 1.0 - 7.8 Gy; 2.0 - 9.6 Gy, 3.9 - 16.4 Gy and 5.9 - 20.3 Gy. The 'see-saw' effect in changes of LQ coefficients was confirmed by re-fitting datasets published by other laboratories. CONCLUSIONS: The classical LQ model with fixed coefficients appears to have limited applicability for cytogenetic dosimetry at radiation doses >5 Gy due to the saturation of the dose response. Different response of the LQ coefficients to the changes of the dose range must be considered during the DRC construction. Proper selection of minimum and maximum dose in calibration experiments makes it possible to improve the goodness of fit of the LQ DRC.


Subject(s)
Chromosome Aberrations , Dose-Response Relationship, Radiation , Gamma Rays , Humans , Chromosome Aberrations/radiation effects , Cytogenetic Analysis , Lymphocytes/radiation effects , Radiation Dosage , Radiometry/methods
8.
Int J Mol Sci ; 25(7)2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38612873

ABSTRACT

The Philadelphia chromosome-negative myeloproliferative neoplasms (Ph-MPNs) are a heterogeneous group of clonal hematopoietic malignancies that include polycythemia vera (PV), essential thrombocythemia (ET), and the prefibrotic form of primary myelofibrosis (prePMF). In this study, we retrospectively reviewed the karyotypes from conventional cytogenetics (CC) and array Comparative Genomic Hybridization + Single Nucleotide Polymorphism (aCGH + SNP) in patients with ET or prePMF to determine whether the combined analysis of both methodologies can identify patients who may be at a higher risk of disease progression. We performed a comprehensive genomic review on 169 patients with a clinical diagnosis of ET (154 patients) or prePMF (15 patients). Genomic alterations detected by CC or array-CGH + SNP were detected in 36% of patients. In patients who progressed, 68% had an abnormal genomic finding by either technology. There was a shorter progression-free survival (PFS) among patients who were cytogenetically abnormal or who were cytogenetically normal but had an abnormal aCGH + SNP result. Leveraging the ability to detect submicroscopic copy number alterations and regions of copy neutral-loss of heterozygosity, we identified a higher number of patients harboring genomic abnormalities than previously reported. These results underscore the importance of genomic analysis in prognostication and provide valuable information for clinical management and treatment decisions.


Subject(s)
Primary Myelofibrosis , Thrombocythemia, Essential , Humans , Comparative Genomic Hybridization , Thrombocythemia, Essential/diagnosis , Thrombocythemia, Essential/genetics , Polymorphism, Single Nucleotide , Primary Myelofibrosis/diagnosis , Primary Myelofibrosis/genetics , Retrospective Studies , Cytogenetic Analysis , Disease Progression
9.
Methods Mol Biol ; 2787: 95-103, 2024.
Article in English | MEDLINE | ID: mdl-38656484

ABSTRACT

Our method describes how to collect forest tree root tips in the field, to store them for transfer to the lab, to pretreat root tips in order to arrest cells in metaphase, fix root tips to preserve specific morphological organizations, to stain fixed root tips by Feulgen's Reaction in order to increase contrast, and to prepare the root meristem for analyzing mitotic stages and chromosomal aberrations via light microscopy. We further describe how to classify chromosomal abnormalities and quantify them via aberration indices.


Subject(s)
Meristem , Trees , Meristem/genetics , Trees/genetics , Chromosome Aberrations , Plant Roots/genetics , Plant Roots/growth & development , Cytogenetic Analysis/methods
10.
JAMA Netw Open ; 7(3): e243689, 2024 Mar 04.
Article in English | MEDLINE | ID: mdl-38530313

ABSTRACT

Importance: Ultrasonographic measurement of fetal nuchal translucency is used in prenatal screening for trisomies 21 and 18 and other conditions. A cutoff of 3.5 mm or greater is commonly used to offer follow-up investigations, such as prenatal cell-free DNA (cfDNA) screening or cytogenetic testing. Recent studies showed a possible association with chromosomal anomalies for levels less than 3.5 mm, but extant evidence has limitations. Objective: To evaluate the association between different nuchal translucency measurements and cytogenetic outcomes on a population level. Design, Setting, and Participants: This population-based retrospective cohort study used data from the Better Outcomes Registry & Network, the perinatal registry for Ontario, Canada. All singleton pregnancies with an estimated date of delivery from September 1, 2016, to March 31, 2021, were included. Data were analyzed from March 17 to August 14, 2023. Exposures: Nuchal translucency measurements were identified through multiple-marker screening results. Main Outcomes and Measures: Chromosomal anomalies were identified through all Ontario laboratory-generated prenatal and postnatal cytogenetic tests. Cytogenetic testing results, supplemented with information from cfDNA screening and clinical examination at birth, were used to identify pregnancies without chromosomal anomalies. Multivariable modified Poisson regression with robust variance estimation and adjustment for gestational age was used to compare cytogenetic outcomes for pregnancies with varying nuchal translucency measurement categories and a reference group with nuchal translucency less than 2.0 mm. Results: Of 414 268 pregnancies included in the study (mean [SD] maternal age at estimated delivery date, 31.5 [4.7] years), 359 807 (86.9%) had a nuchal translucency less than 2.0 mm; the prevalence of chromosomal anomalies in this group was 0.5%. An increased risk of chromosomal anomalies was associated with increasing nuchal translucency measurements, with an adjusted risk ratio (ARR) of 20.33 (95% CI, 17.58-23.52) and adjusted risk difference (ARD) of 9.94% (95% CI, 8.49%-11.39%) for pregnancies with measurements of 3.0 to less than 3.5 mm. The ARR was 4.97 (95% CI, 3.45-7.17) and the ARD was 1.40% (95% CI, 0.77%-2.04%) when restricted to chromosomal anomalies beyond the commonly screened aneuploidies (excluding trisomies 21, 18, and 13 and sex chromosome aneuploidies). Conclusions and Relevance: In this cohort study of 414 268 singleton pregnancies, those with nuchal translucency measurements less than 2.0 mm were at the lowest risk of chromosomal anomalies. Risk increased with increasing measurements, including measurements less than 3.5 mm and anomalies not routinely screened by many prenatal genetic screening programs.


Subject(s)
Cell-Free Nucleic Acids , Down Syndrome , Infant, Newborn , Female , Pregnancy , Humans , Child, Preschool , Nuchal Translucency Measurement , Cohort Studies , Retrospective Studies , Trisomy , Aneuploidy , Cytogenetic Analysis , Ontario/epidemiology
11.
Sci Rep ; 14(1): 6962, 2024 03 23.
Article in English | MEDLINE | ID: mdl-38521884

ABSTRACT

Salinity is one of the most important abiotic stress factors that negatively affect plant growth and development. In contrast, fusaric acid (FA), a mycotoxin produced by Fusarium and Giberella fungal genera, has biological and metabolic effects in various plants. In this study, it was aimed to investigate the protective effect of externally applied FA (0.1 nM) against the damage caused by salt (0.15 M NaCl) stress in onion (Allium cepa L.) plant. Salt stress resulted in an increase in the chromosomal aberrations (CAs) and micronucleus (MN) frequency, a decrease in the mitotic index (MI), fresh weight, root number, germination percentage, and root length. It promoted CAs such as irregular mitosis, bilobulated nuclei, chromosome loss, bridge, unequal seperation of chromosome, vagrant chromosome and polar slip in root meristem cells. In addition, salt stress caused a enhancement in free proline (PR), catalase (CAT), superoxide dismutase (SOD) and malondialdehyde (MDA) contents in the roots of onion plant. Moreover, it revealed damage and changes that include the accumulation of some chemical substances such as proline and sugars in epidermis and cortex layer cells, epidermal cell injury, flattening of the cell nucleus, wall thickening in cortex cells, necrotic areas and indistinct transmission tissue in the anatomical structure of onion roots. On the other hand, FA application promoted bulb germination and mitotic activity, strengthened the antioxidant defense system, and reduced chromosome and anatomical structure damages. In conclusion; it has been revealed that exogenous FA application may have a positive effect on increasing the resistance of onion plants to salt stress.


Subject(s)
Mycotoxins , Onions , Fusaric Acid/pharmacology , Sodium Chloride/pharmacology , Sodium Chloride/metabolism , Mycotoxins/metabolism , Antioxidants/pharmacology , Antioxidants/metabolism , Plant Roots/metabolism , Proline/metabolism , Cytogenetic Analysis
12.
J Clin Exp Hematop ; 64(1): 10-20, 2024.
Article in English | MEDLINE | ID: mdl-38538316

ABSTRACT

High-risk cytogenetic abnormalities (HRCAs) influence the prognosis of multiple myeloma (MM). However, additional cytogenetic aberrations can lead to poor outcomes. This study aimed to clarify whether HRCAs and additional chromosomal abnormalities affect MM prognosis. Patients with newly diagnosed MM who were treated with novel agents were retrospectively evaluated. The primary objective was to assess the difference in progression-free survival (PFS) and overall survival (OS) between patients with/without HRCAs and between patients with/without complex karyotype (CK). The secondary objectives were to identify factors affecting PFS/OS and factors related to CK. HRCAs were defined as del(17p), t(4;14), t(14;16), and gain/amplification(1q) assessed using fluorescence in situ hybridization. CK was defined as ≥3 chromosomal abnormalities on G-banding. Among 110 patients, 40 had HRCAs and 15 had CK. In this study, survival durations between patients with/without HRCAs were similar, while the CK group had significantly poorer PFS/OS than the no-CK group (median PFS: 9 vs. 24 months and median OS: 29 vs. 97 months, respectively), and a poor prognostic impact of CK was maintained in patients with HRCAs. In multivariate analysis, CK was correlated with poor PFS/OS (hazard ratio [HR]: 2.39, 95% confidence interval [95% CI]: 1.22-4.66 and HR: 2.66, 95% CI: 1.10-6.45, respectively). Bone marrow plasma cell (BMPC) ≥60% (odds ratio [OR] = 6.40, 95% CI: 1.50-27.2) and Revised International Staging System III (OR = 7.53, 95% CI: 2.09-27.1) were associated with CK. Our study suggests that CK may contribute to the poor prognosis of MM. Aggressive disease status including high BMPC proliferation could be relevant to CK.


Subject(s)
Multiple Myeloma , Humans , Multiple Myeloma/diagnosis , Multiple Myeloma/genetics , Multiple Myeloma/therapy , Prognosis , In Situ Hybridization, Fluorescence , Retrospective Studies , Cytogenetic Analysis , Chromosome Aberrations , Karyotype
15.
Best Pract Res Clin Haematol ; 37(1): 101539, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38490767

ABSTRACT

Improvements made during the last decades in the management of patients with hematologic neoplasia have resulted in increase of overall survival. These advancements have become possible through progress in our understanding of genetic basis of different hematologic malignancies and their role in the current risk-adapted treatment protocols. In this review, we provide an overview of current cytogenetic and molecular genetic methods, commonly used in the genetic characterization of hematologic malignancies, describe the current developments in the cytogenetic and molecular diagnostics, and give an outlook into their future development. Furthermore, we give a brief overview of the most important public databases and guidelines for sequence variant interpretation.


Subject(s)
Hematologic Neoplasms , Humans , Hematologic Neoplasms/diagnosis , Hematologic Neoplasms/genetics , Cytogenetic Analysis , Molecular Biology
16.
Best Pract Res Clin Haematol ; 37(1): 101533, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38490763

ABSTRACT

The diversity of genetic and genomic abnormalities observed in acute myeloid leukemia (AML) reflects the complexity of these hematologic neoplasms. The detection of cytogenetic and molecular alterations is fundamental to diagnosis, risk stratification and treatment of AML. Chromosome rearrangements are well established in the diagnostic classification of AML, as are some gene mutations, in several international classification systems. Additionally, the detection of new mutational profiles at relapse and identification of mutations in the pre- and post-transplant settings are illuminating in understanding disease evolution and are relevant to the risk assessment of AML patients. In this review, we discuss recurrent cytogenetic abnormalities, as well as the detection of recurrent mutations, within the context of a normal karyotype, and in the setting of chromosome abnormalities. Two new classification schemes from the WHO and ICC are described, comparing these classifications in terms of diagnostic criteria and entity definition in AML. Finally, we discuss ways in which genomic sequencing can condense the detection of gene mutations and chromosome abnormalities into a single assay.


Subject(s)
Leukemia, Myeloid, Acute , Humans , Leukemia, Myeloid, Acute/diagnosis , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/therapy , Chromosome Aberrations , Mutation , Genomics , Cytogenetic Analysis
17.
PLoS One ; 19(3): e0300477, 2024.
Article in English | MEDLINE | ID: mdl-38466706

ABSTRACT

Acute myeloid leukemia (AML) is an aggressive and lethal cancer of the blood, which leads to the death of over 11,000 patients in the United States each year. Research on identifying, characterizing, and treating AML is crucial in the fight against this deadly disease. Recent studies have examined the role of CLEC11A in cancer, including AML. However, there have been conflicting reports related to tumor progression and survival. Because survival is based on a variety of factors, including classification of the tumor, genetic risk factors, and demographics, it is imperative that we determine what role CLEC11A may have in cancer survival. Therefore, utilizing data from the Genomic Data Commons, we analyzed CLEC11A methylation in 108 AML patients compared to FAB classification, cytogenetic risk factors, age, race, and gender. Our results show statistically significant correlations between methylation of CLEC11A and FAB classification as well as poor genetic risk factors. However, no difference was observed in CLEC11A methylation when compared to demographic data. Our results, matched with a known biological function of CLEC11A in early hematopoiesis, indicate that CLEC11A may be an important marker for AML diagnosis and prognosis and provide relevant data in the ongoing search for novel therapeutics to improve AML survival.


Subject(s)
Leukemia, Myeloid, Acute , Humans , Cytogenetic Analysis , Demography , Leukemia, Myeloid, Acute/pathology , Methylation , Prognosis , Risk Factors
18.
Article in English | MEDLINE | ID: mdl-38432778

ABSTRACT

The dosimetry and control of exposure for individuals chronically exposed to ionizing radiation are important and complex issues. Assessment may be optimized by evaluating individual adaptation and radiosensitivity, but it is not possible for a single model to account for all relevant parameters. Our goal was to develop approaches for the calculation of doses for persons chronically exposed to ionizing radiation, taking their radiosensitivities into consideration. On the basis of ex vivo radiation of blood samples, dose-effect models were constructed for dose ranges 0.01-2.0 and 0.01-0.4 Gy, using different cytogenetic criteria. The frequencies of "dicentric chromosomes and rings" at low doses are too low to have predictive value. The different responses of subjects to radiation made it possible to categorize them according to their radiosensitivities and to generate separate dose-effect curves for radiosensitive, average, and radioresistant individuals, reducing the amount of error in retrospective dosimetry.


Subject(s)
Radiation Tolerance , Radiation, Ionizing , Humans , Retrospective Studies , Cytogenetics , Radiation Tolerance/genetics , Cytogenetic Analysis
19.
J Mol Diagn ; 26(5): 374-386, 2024 May.
Article in English | MEDLINE | ID: mdl-38395407

ABSTRACT

Soft-tissue and bone tumors represent a heterogeneous group of tumors encompassing more than 100 histologic subtypes today. Identifying genetic aberrations increasingly is important in these tumors for accurate diagnosis. Although gene mutations typically are detected by second-generation sequencing, the identification of structural variants (SVs) and copy number alterations (CNAs) remains challenging and requires various cytogenetic techniques including karyotyping, fluorescence in situ hybridization, and arrays, each with important limitations. Optical Genome Mapping (OGM), a non-sequencing-based technique for high-resolution detection of SVs and CNAs, was applied in a retrospective series of diagnostic soft-tissue and bone tumor samples. Sample preparation was successful in 38 of 53 cases, with the highest success rate in nonadipocytic soft-tissue tumors (24 of 27 cases; 89%). In 32 of 35 cases carrying a diagnostic SV or CNA, OGM identified the aberration (91%), including a POU2AF3::EWSR1 fusion in a round cell sarcoma and a translocation t(1;5)(p22;p15) in a myxoinflammatory fibroblastic sarcoma. Interestingly, OGM shed light on the genomic complexity underlying the various aberrations. In five samples, OGM showed that chains of rearrangements generated the diagnostic fusion, three of which involved chromoplexy. In addition, in nine samples, chromothripsis was causal to the formation of giant marker/ring/double-minute chromosomes. Finally, compared with standard-of-care cytogenetics, OGM revealed additional aberrations, requiring further investigation of their potential clinical relevance.


Subject(s)
Bone Neoplasms , Sarcoma , Humans , In Situ Hybridization, Fluorescence , Retrospective Studies , Cytogenetic Analysis , Sarcoma/genetics , Bone Neoplasms/diagnosis , Bone Neoplasms/genetics , Bone Neoplasms/pathology , Chromosome Mapping
20.
Clin Cancer Res ; 30(7): 1319-1326, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38300723

ABSTRACT

PURPOSE: Hypomethylating agents (HMA) combined with venetoclax are an emerging therapeutic strategy for higher-risk myelodysplastic syndromes (HR-MDS). The cytogenetic and molecular factors associated with outcomes with this combination for HR-MDS are incompletely understood. EXPERIMENTAL DESIGN: We pooled patient data from 3 prospective trials evaluating HMA-venetoclax in HR-MDS to study associations between cytogenetic and molecular factors and overall response rate (ORR), overall survival (OS), and event-free survival (EFS). The Kaplan-Meier method was used to estimate time-to-event endpoints. Univariate and multivariate analyses using logistic regression (for ORR) or the Cox proportional hazards model (for OS and EFS) were used to identify associations between clinical, cytogenetic, and molecular factors and outcomes. RESULTS: A total of 80 patients (52 HMA-naïve, 28 HMA-failure) were included. ORR was 90% in HMA-naïve and 57% in HMA-failure. Median OS was 28.2 and 8.3 months in HMA-naïve and HMA-failure, respectively. Median EFS was 17.9 and 5.5 months in HMA-naïve and HMA-failure, respectively. In addition, 24/52 (46%) of the HMA-naïve and 3/28 (11%) of the HMA-failure patients proceeded to allogeneic stem cell transplantation (SCT). Factors associated with inferior outcomes were prior HMA failure, complex cytogenetics, trisomy 8, TP53 mutations, and RAS pathway mutations. Mutations in RNA splicing, DNA methylation, and ASXL1 appeared favorable. Blast percentage was not predictive of outcomes. CONCLUSIONS: Knowledge of cytogenetic and molecular alterations may help identify which patients with HR-MDS benefit the most from venetoclax.


Subject(s)
Bridged Bicyclo Compounds, Heterocyclic , Myelodysplastic Syndromes , Sulfonamides , Humans , Myelodysplastic Syndromes/drug therapy , Myelodysplastic Syndromes/genetics , Prospective Studies , DNA Methylation , Cytogenetic Analysis , Retrospective Studies
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