Chromosomal Gene Research Articles

Marker Assisted Characterization of TGMS Gene in Rice Cultigen Ts 29 (Oryza Sativa L.) to Develop Two Line Hybrids

The application of the thermsensitive genic male sterility (TGMS) system has great potential for revolutionizing hybrid rice production through simple and effective seed production technology. For the successful utilization of this novel male sterility system, knowledge of the fertility behaviour and genetic control of a TGMS line is essential. In this study, an investigation was carried out to characterize the TGMS gene present in the mapping population of TS 29 x CO(R)49. Through Bulk Segregant Analysis RM 3476 alone produced a polymorphic relationship between the parents and corresponding bulks and was used for surveying the individual plants of F3/F4 population. The marker RM 3476 produced contrasting fragments between sterile and fertile plants. The result was associated with the phenotypic observations on pollen fertility under the field conditions, confirming co-segregation of the marker with the gene of interest. Hence, the tight linkage of marker with TGMS gene was identified by RM 3476 which was already identified as a marker located near tms 6 gene in chromosome 5. From this study four TGMS lines were also identified with desirable floral traits for high out crossing and medium slender grain type. Bangladesh J. Bot. 53(2): 345-351, 2024 (June)

Physical chromosomal mapping of major ribosomal genes in 15 ant species with a review of hypotheses regarding evolution of the number and position of NORs in ants.

Recently, hypotheses regarding the evolutionary patterns of ribosomal genes in ant chromosomes have been under discussion. One of these hypotheses proposes a relationship between chromosomal location and the number of rDNA sites, suggesting that terminal locations facilitate the dispersion of rDNA clusters through ectopic recombination during meiosis, while intrachromosomal locations restrict them to a single chromosome pair. Another hypothesis suggests that the multiplication of rDNA sites could be associated with an increase in the chromosome number in Hymenoptera due to chromosomal fissions. In this study, we physically mapped rDNA sites in 15 new ant species and also reviewed data on rDNA available since the revision by Teixeira et al. (2021a). Our objectives were to investigate whether the new data confirm the relationship between chromosomal location and the number of rDNA sites, and whether the increase in the chromosome number is significant in the dispersion of rDNA clusters in ant karyotypes. Combining our new data with all information on ant cytogenetics published after 2021, 40 new species and nine new genera were assembled. Most species exhibited intrachromosomal rDNA sites on a single chromosome pair, while three species showed these genes in terminal regions of multiple chromosome pairs. On one hand, the hypothesis that the chromosomal location of rDNA clusters may facilitate the dispersion of rDNA sites in the ant genome, as previously discussed, was strengthened, but, on the other hand, the hypothesis of chromosomal fission as the main mechanism for dispersion of ribosomal genes in ants is likely to be refuted. Furthermore, in certain genera, the location of rDNA sites remained similar among the species studied, whereas in others, the distribution of these genes showed significant variation between species, suggesting a more dynamic chromosomal evolution.

Detection of Klebsiella pneumoniae Carbapenem Resistance Genes by qPCR: Choosing the Right Method for Total DNA Extraction.

Rapid and accurate detection of Klebsiella pneumoniae carbapenem resistance is important for infection control and targeted antibiotic therapy. PCR-based assay performance heavily depends on the quality and quantity of template DNA. Challenges arise from the necessity to isolate chromosomal and large plasmid-encoded resistance genes simultaneously from a limited number of target cells and to remove PCR inhibitors. qPCRs for the detection of K. pneumoniae strains carrying blaOXA-48, blaNDM-1, blaKPC-2, and blaVIM-1 carbapenemase genes were developed. We compared the performance of template DNA extracted with silica column-based methods, reversed elution systems, and lysis-only methods either from diluted culture fluid or from a synthetic stool matrix which contained PCR inhibitors typically present in stool. The synthetic stool matrix was chosen to mimic K. pneumoniae containing rectal swabs or stool samples in a reproducible manner. For total DNA isolated from culture fluid, resistance gene detection by qPCR was always possible, independent of the extraction method. However, when total DNA was isolated from synthetic stool matrix spiked with K. pneumoniae, most methods were insufficient. The best performance of template DNA was obtained with reversed elution. This highlights the importance of choosing the right DNA extraction method for consistent carbapenem resistance detection by PCR.

Molecular Dating of the Teleost Whole Genome Duplication (3R) Is Compatible With the Expectations of Delayed Rediploidization.

Vertebrate evolution has been punctuated by three whole genome duplication events that have been implicated causally in phenotypic evolution, from the origin of phenotypic novelties to explosive diversification. Arguably, the most dramatic of these is the 3R whole genome duplication event associated with the origin of teleost fishes which comprise more than half of all living vertebrate species. However, tests of a causal relationship between whole genome duplication and teleost diversification have proven difficult due to the challenge of establishing the timing of these phenomena. Here we show, based on molecular clock dating of concatenated gene alignments, that the 3R whole genome duplication event occurred in the early-middle Permian (286.18 to 267.20 million years ago; Ma), 52.02 to 12.84 million years (Myr) before the divergence of crown-teleosts in the latest Permian-earliest Late Triassic (254.36 to 234.16 Ma) and long before the major pulses of teleost diversification in Ostariophysi and Percomorpha (56.37 to 100.17 Myr and at least 139.24 to 183.29 Myr later, respectively). The extent of this temporal gap between putative cause and effect precludes 3R as a deterministic driver of teleost diversification. However, these age constraints remain compatible with the expectations of a prolonged rediploidization process following whole genome duplication which, through the effects of chromosome rearrangement and gene loss, remains a viable mechanism to explain the evolution of teleost novelties and diversification.

YABBY transcription factor family in the octoploid Fragaria × ananassa and five diploid Fragaria species.

YABBY genes encode specific TFs of seed plants involved in development and formation of leaves, flowers, and fruit. In the present work, genome-wide and expression analyses of the YABBY gene family were performed in six species of the Fragaria genus: Fragaria × ananassa, F.daltoniana, F.nilgerrensis, F.pentaphylla, F.viridis, and F.vesca. The chromosomal location, synteny pattern, gene structure, and phylogenetic analyses were carried out. By combining RNA-seq data and RT-qPCR analysis we explored specific expression of YABBYs in F. × ananassa and F.vesca. We also analysed the promoter regions of FaYABBYs and performed MeJA application to F. × ananassa fruit to observe effects on gene expression. We identified and characterized 25 YABBY genes in F. × ananassa and six in each of the other five species, which belong to FIL/YAB3 (YABBY1), YAB2 (YABBY2), YAB5 (YABBY5), CRC, and INO clades previously described. Division of the YABBY1 clade into YABBY1.1 and YABBY1.2 subclades is reported. We observed differential expression according to tissue, where some FaYABBYs are expressed mainly in leaves and flowers and to a minor extent during fruit development of F. × ananassa. Specifically, the FaINO genes contain jasmonate-responsive cis-acting elements in their promoters which may be functional since FaINOs are upregulated in F. × ananassa fruit under MeJA treatment. This study suggests that YABBY TFs play an important role in the development- and environment-associated responses of the Fragaria genus.

Spatial Chromosome Organization and Adaptation of Escherichia coli under Heat Stress.

The spatial organization of bacterial chromosomes is crucial for cellular functions. It remains unclear how bacterial chromosomes adapt to high-temperature stress. This study delves into the 3D genome architecture and transcriptomic responses of Escherichia coli under heat-stress conditions to unravel the intricate interplay between the chromosome structure and environmental cues. By examining the role of macrodomains, chromosome interaction domains (CIDs), and nucleoid-associated proteins (NAPs), this work unveils the dynamic changes in chromosome conformation and gene expression patterns induced by high-temperature stress. It was observed that, under heat stress, the short-range interaction frequency of the chromosomes decreased, while the long-range interaction frequency of the Ter macrodomain increased. Furthermore, two metrics, namely, Global Compactness (GC) and Local Compactness (LC), were devised to measure and compare the compactness of the chromosomes based on their 3D structure models. The findings in this work shed light on the molecular mechanisms underlying thermal adaptation and chromosomal organization in bacterial cells, offering valuable insights into the complex inter-relationships between environmental stimuli and genomic responses.

Genome-Wide Identification of WRKY Transcription Factor Family in Chinese Rose and Response to Drought, Heat, and Salt Stress.

The WRKY gene family is a key transcription factor family for plant development and the stress response. However, few studies have investigated the WRKY gene family in Chinese rose (Rosa chinensis). In this study, 68 RcWRKY genes were identified from the Chinese rose genome and classified into three primary groups and five subgroups based on the structural and phylogenetic characteristics. The analysis of the conserved domains, motifs, and gene structure revealed that the RcWRKY genes within the same group had the same exon-intron organization and composition. Chromosome mapping and gene duplication revealed that the RcWRKY genes were randomly dispersed across seven chromosomes. Fragment duplication and refined selection may have influenced the evolution of the WRKY gene family in Chinese rose. The cis-acting elements in the WRKY promoter region revealed that the RcWRKY genes contained numerous abiotic stress response elements. The results of qRT-PCR revealed that the expression of RcWRKY was tissue-specific, with high expression being observed under drought, heat, and salt stress. Notably, RcWRKY49's expression increased more than fivefold following salt stress, indicating that it is a crucial gene mediating the salt stress response of Chinese rose. These findings shed light on the regulatory role of RcWRKY in the growth and development of Chinese rose, and they serve as a foundation for future molecular breeding programs and gene discovery.

Beckwith-Wiedemann syndrome with Hirschsprung’s disease in a newborn case report and literature review

Background: Beckwith-Wiedemann Syndrome (BWS) is a genetic condition related to changes in the genes of chromosome 11 which result in the overgrowth of many parts of the body and are associated with multiple congenital anomalies. Hirschsprung’s disease is a congenital disorder characterized by a complete absence of ganglion cells in the myenteric and submucosal plexus of the colon. So far, only 2 patients with Beckwith-Wiedemann syndrome and intestinal obstruction due to Hirschsprung’s disease were reported.

Chromosomal qnrB19-carrying Escherichia coli isolated from the stool sample of a community resident in Ecuador.

We identified a chromosomal qnrB19 gene within a transposon in a colistin-resistant Escherichia coli strain isolated from the stool sample of an Ecuadorian resident. This finding suggests a more stable acquisition of quinolone resistance on chromosomes than that on plasmids and the potential for propagation to other DNA structures.

Single cell regulatory architecture of human pancreatic islets suggests sex differences in β cell function and the pathogenesis of type 2 diabetes.

Biological sex affects the pathogenesis of type 2 and type 1 diabetes (T2D, T1D) including the development of β cell failure observed more often in males. The mechanisms that drive sex differences in β cell failure is unknown. Studying sex differences in islet regulation and function represent a unique avenue to understand the sex-specific heterogeneity in β cell failure in diabetes. Here, we examined sex and race differences in human pancreatic islets from up to 52 donors with and without T2D (including 37 donors from the Human Pancreas Analysis Program [HPAP] dataset) using an orthogonal series of experiments including single cell RNA-seq (scRNA-seq), single nucleus assay for transposase-accessible chromatin sequencing (snATAC-seq), dynamic hormone secretion, and bioenergetics. In cultured islets from nondiabetic (ND) donors, in the absence of the in vivo hormonal environment, sex differences in islet cell type gene accessibility and expression predominantly involved sex chromosomes. Of particular interest were sex differences in the X-linked KDM6A and Y-linked KDM5D chromatin remodelers in female and male islet cells respectively. Islets from T2D donors exhibited similar sex differences in differentially expressed genes (DEGs) from sex chromosomes. However, in contrast to islets from ND donors, islets from T2D donors exhibited major sex differences in DEGs from autosomes. Comparing β cells from T2D and ND donors revealed that females had more DEGs from autosomes compared to male β cells. Gene set enrichment analysis of female β cell DEGs showed a suppression of oxidative phosphorylation and electron transport chain pathways, while male β cell had suppressed insulin secretion pathways. Thus, although sex-specific differences in gene accessibility and expression of cultured ND human islets predominantly affect sex chromosome genes, major differences in autosomal gene expression between sexes appear during the transition to T2D and which highlight mitochondrial failure in female β cells.

Copy number variations of CCND1 gene and chromosome 11 centromere in acral melanoma

Objective: To study the correlation between the copy number variations of CCND1 gene and chromosome 11 and their associations with clinicopathologic features in acral melanoma. Methods: Thirty-three acral melanoma cases diagnosed at the Department of Pathology of Peking University Third Hospital, Beijing, China from January 2018 to August 2021 were collected. Fluorescence in situ hybridization (FISH) was used to detect the copy number of CCND1 gene and centromere of chromosome 11. The relationship between the copy numbers of CCND1 and chromosome 11 centromere, and the correlation between CCND1 copy number and clinicopathologic characteristics were analyzed. Results: There were 15 male and 18 female patients, with an age ranging from 22-86 years. 63.6% (21/33) of the patients had an increased CCND1 gene copy number. 21.2% (7/33) of patients with increased CCND1 copy number had an accompanying chromosome 11 centromere copy number increase. 27.3% (9/33) of the cases had a low copy number of CCND1 gene, and 4 of them (4/33, 12.1%) were accompanied by chromosome 11 centromere copy number increase. 36.4% (12/33) of the cases had a high copy number of CCND1 gene, and 3 (3/33, 9.1%) of them were accompanied by chromosome 11 centromere copy number increase. No cases with CCND1 low copy number increase showed CCND1/CEP11 ratio greater than 2.00. The 11 cases with CCND1 high copy number increase showed CCND1/CEP11 ratio greater than or equal to 2.00. However, there was no significant correlation between CCND1 copy number increase and any of the examined clinicopathologic features such as age, sex, histological type, Breslow thickness, ulcer and Clark level. Conclusions: CCND1 copy number increase is a significant molecular alteration in acral melanoma. In some cases, CCND1 copy number increase may be accompanied by the copy number increase of chromosome 11. For these cases the copy number increase in CCND1 gene may be a result of the copy number change of chromosome 11.

Selection Shapes the Genomic Landscape of Introgressed Ancestry in a Pair of Sympatric Sea Urchin Species.

A growing number of recent studies have demonstrated that introgression is common across the tree of life. However, we still have a limited understanding of the fate and fitness consequence of introgressed variation at the whole-genome scale across diverse taxonomic groups. Here, we implemented a phylogenetic hidden Markov model to identify and characterize introgressed genomic regions in a pair of well-diverged, nonsister sea urchin species: Strongylocentrotus pallidus and Strongylocentrotus droebachiensis. Despite the old age of introgression, a sizable fraction of the genome (1% to 5%) exhibited introgressed ancestry, including numerous genes showing signals of historical positive selection that may represent cases of adaptive introgression. One striking result was the overrepresentation of hyalin genes in the identified introgressed regions despite observing considerable overall evidence of selection against introgression. There was a negative correlation between introgression and chromosome gene density, and two chromosomes were observed with considerably reduced introgression. Relative to the nonintrogressed genome-wide background, introgressed regions had significantly reduced nucleotide divergence (dXY) and overlapped fewer protein-coding genes, coding bases, and genes with a history of positive selection. Additionally, genes residing within introgressed regions showed slower rates of evolution (dN, dS, dN/dS) than random samples of genes without introgressed ancestry. Overall, our findings are consistent with widespread selection against introgressed ancestry across the genome and suggest that slowly evolving, low-divergence genomic regions are more likely to move between species and avoid negative selection following hybridization and introgression.

Sex differences in acute early life stress-enhanced fear learning in adult rats.

Patients diagnosed with posttraumatic stress disorder (PTSD) present with a spectrum of debilitating anxiety symptoms resulting from exposure to trauma. Women are twice as likely to be diagnosed with anxiety and PTSD compared to men; however, the reason for this vulnerability remains unknown. We conducted four experiments where we first demonstrated a female vulnerability to stress-enhanced fear learning (SEFL) with a moderate, acute early life stress (aELS) exposure (4 footshocks in a single session), compared to a more intense aELS exposure (15 footshocks in a single session) where males and females demonstrated comparable SEFL. Next, we demonstrated that this female vulnerability does not result from differences in footshock reactivity or contextual fear conditioning during the aELS exposure. Finally, using gonadectomy or sham surgeries in adult male and female rats, we showed that circulating levels of gonadal steroid hormones at the time of adult fear conditioning do not explain the female vulnerability to SEFL. Additional research is needed to determine whether this vulnerability can be explained by organizational effects of gonadal steroid hormones or differences in sex chromosome gene expression. Doing so is critical for a better understanding of increased female vulnerability to certain psychiatric diseases.

Clinical Impact of C-myc Oncogenic Diversity on Solid and Lymphoid Malignancies.

Onset and progression of malignant tumors is a multistep process including a variety of gross chromosomal and specific genes' deregulation. Among oncogenes that are frequently altered in solid and also in hematological malignancies, the C-myc (gene locus: 8q24.21) plays a pivotal role. C-myc is a proto-oncogene encoding for a nuclear phosphoprotein implicated in cell cycle progression, apoptosis and cellular differentiation and transformation. The purpose of the current molecular review was to explore the differences of C-myc oncogenic activity in solid and lymphoid malignancies that modify its clinical impact on them. A systematic review of the literature in the international database PubMed was carried out. The year 2010 was set as a prominent time limit for the publication date of articles in the majority of them, whereas specific references of great importance and historical value in the field of C-myc gene discovery and analysis were also included. The following keywords were used: C-myc, oncogene, signaling pathway, malignancies, carcinoma, lymphoma. A pool of 43 important articles were selected for the present study at the basis of combining molecular knowledge with new targeted therapeutic strategies. C-myc oncogene demonstrates two different mechanisms of deregulation: amplification, mutation and translocation patterns. These particular aspects of gene alteration are unique for solid and non-solid (hematological) malignancies, respectively. C-myc is characterized by diversity regarding its deregulation mechanisms in malignancies derived from different tissues. C-myc translocation is sporadically combined with amplification ("complicon" formation) or mutations creating exotic genetic signatures. This "bi-phasic" C-myc deregulation model in the corresponding malignant tumor categories clinically affects the corresponding patients, also modifying the targeted therapeutic strategies on them.

C-Jun Transcription Factor Oncogenic Activation in Oral Carcinoma.

Oral carcinogenetic is based on a variety of genomic imbalances (gross chromosome or specific gene alterations) that drive the normal oral mucosa to its neoplastic/dysplastic epithelial form and finally to a totally malignant tissue transformation. In this multi-step procedure, down-regulation of suppressor genes combined with overactivation of oncogenes are two crucial and partially early genetic events involved in the onset and progression of neoplastic/malignant epithelia transformation. More specifically, deregulation of strong transcription factors negatively affects the normal expression of a broad spectrum of genes that are involved in cell proliferation and signalling transduction to the nucleus. The purpose of the current molecular review was to explore the c-Jun (chromosome location: 1p32-p31) transcription factor transformation mechanisms to oncogene in oral squamous cell carcinoma (OSCC). A systematic review of the literature was carried out by searching in PubMed international database. The year 2010 was set as a prominent time limit for the publication date of the articles in the majority of them, whereas specific references of great importance and historical value in the field of the c-Jun gene discovery and analysis were also included. The following keywords were used: c-Jun, oncogene, signaling pathway, oral, carcinoma, transcription. A pool of 45 important articles were selected for the present study at the basis of combining molecular knowledge with new targeted therapeutic strategies. C-Jun - as a part of the c-Jun/c-Fos transcription factors' complex -critically regulates the expression levels in a variety of genes inside the cellular microenvironment. A broad spectrum of malignancies, including OSCC, demonstrate c-Jun alterations driving the gene to its oncogenic phenotype. Interestingly, c-Jun oncogenic activation is mediated by high-risk human papilloma virus (HR-HPV) persistent infection in significant subsets of these malignancies. C-Jun was the first oncogene - acting as a strong transcription factor - that was discovered and cloned 35 years ago. C-Jun is the living history of oncogenes and its discovery marks a significant step in the evolution of molecular biology.

X-chromosome inactivation in human iPSCs provides insight into X-regulated gene expression in autosomes

BackgroundVariation in X chromosome inactivation (XCI) in human-induced pluripotent stem cells (hiPSCs) can impact their ability to model biological sex biases. The gene-wise landscape of X chromosome gene dosage remains unresolved in female hiPSCs. To characterize patterns of de-repression and escape from inactivation, we performed a systematic survey of allele specific expression in 165 female hiPSC lines.ResultsXCI erosion is non-random and primarily affects genes that escape XCI in human tissues. Individual genes and cell lines vary in the frequency and degree of de-repression. Bi-allelic expression increases gradually after modest decrease of XIST in cultures, whose loss is commonly used to mark lines with eroded XCI. We identify three clusters of female lines at different stages of XCI. Increased XCI erosion amplifies female-biased expression at hypomethylated sites and regions normally occupied by repressive histone marks, lowering male-biased differences in the X chromosome. In autosomes, erosion modifies sex differences in a dose-dependent way. Male-biased genes are enriched for hypermethylated regions, and de-repression of XIST-bound autosomal genes in female lines attenuates normal male-biased gene expression in eroded lines. XCI erosion can compensate for a dominant loss of function effect in several disease genes.ConclusionsWe present a comprehensive view of X chromosome gene dosage in hiPSCs and implicate a direct mechanism for XCI erosion in regulating autosomal gene expression in trans. The uncommon and variable reactivation of X chromosome genes in female hiPSCs can provide insight into X chromosome’s role in regulating gene expression and sex differences in humans.

The complete sequence and comparative analysis of ape sex chromosomes

Apes possess two sex chromosomes—the male-specific Y chromosome and the X chromosome, which is present in both males and females. The Y chromosome is crucial for male reproduction, with deletions being linked to infertility1. The X chromosome is vital for reproduction and cognition2. Variation in mating patterns and brain function among apes suggests corresponding differences in their sex chromosomes. However, owing to their repetitive nature and incomplete reference assemblies, ape sex chromosomes have been challenging to study. Here, using the methodology developed for the telomere-to-telomere (T2T) human genome, we produced gapless assemblies of the X and Y chromosomes for five great apes (bonobo (Pan paniscus), chimpanzee (Pan troglodytes), western lowland gorilla (Gorilla gorilla gorilla), Bornean orangutan (Pongo pygmaeus) and Sumatran orangutan (Pongo abelii)) and a lesser ape (the siamang gibbon (Symphalangus syndactylus)), and untangled the intricacies of their evolution. Compared with the X chromosomes, the ape Y chromosomes vary greatly in size and have low alignability and high levels of structural rearrangements—owing to the accumulation of lineage-specific ampliconic regions, palindromes, transposable elements and satellites. Many Y chromosome genes expand in multi-copy families and some evolve under purifying selection. Thus, the Y chromosome exhibits dynamic evolution, whereas the X chromosome is more stable. Mapping short-read sequencing data to these assemblies revealed diversity and selection patterns on sex chromosomes of more than 100 individual great apes. These reference assemblies are expected to inform human evolution and conservation genetics of non-human apes, all of which are endangered species.

Identification of SMC2 and SMC4 as prognostic markers in breast cancer through bioinformatics analysis.

Breast cancer (BRCA) is one of the most common malignant tumors. The structural maintenance of chromosome (SMC) gene family has been shown to play an important role in human cancers. However, the role of SMC families in BRCA is unclear. This study aimed to explore the role and potential clinical value of whole SMCs in BRCA. TIMER and UALCAN database were used to analysis the expression level. Genetic variations were analyzed by cBioPortal. Promoter methylation and protein level were analyzed by UCLCAN. GO and KEGG were analyzed by Metascape database. Prognostic value of SMCs was analyzed by Kaplan-Meier and multivariate cox regression analyses. Immune infiltration analysis was conducted by CIBERSORT. Immunotherapy outcome prediction was conducted by Cancer Immunome Atlas. Targeted drug therapy outcome prediction was taken by GDSC and R language. The cell viability was tested by CCK8 and migration was tested by wound healing assay. Xenograft model was used to investigate the in vivo role of SMC2. Expression levels of SMC1A, SMC2, SMC4, SMC5 and SMC6 mRNA were increased in BRCA tissues, and negatively correlated with promoter methylation. Overexpression of SMC2 and SMC4 was negatively correlated with survival. Function of SMCs family regulatory genes was mainly related to ATPase activity. Expression of most SMCs was negatively correlated with immunotherapy and drug therapy outcomes. Interfere SMC2 and SMC4 decreased IC50 values of 5-fluorouracil and oxaliplatin and inhibited the migration of MCF7 cells. Tumor growth and weights were significantly decreased in si-SMC2 groups. Combined bioinformatics and clinical specimen analysis verified SMC2 and SMC4 as independent prognostic factors in BRCA, suggesting their significance for the diagnosis and treatment of BRCA.

Chromosomal damage, gene expression and alternative transcription in human lymphocytes exposed to mixed ionizing radiation as encountered in space

Astronauts travelling in space will be exposed to mixed beams of particle radiation and photons. Exposure limits that correspond to defined cancer risk are calculated by multiplying absorbed doses by a radiation-type specific quality factor that reflects the biological effectiveness of the particle without considering possible interaction with photons. We have shown previously that alpha radiation and X-rays may interact resulting in synergistic DNA damage responses in human peripheral blood lymphocytes but the level of intra-individual variability was high. In order to assess the variability and validate the synergism, blood from two male donors was drawn at 9 time points during 3 seasons of the year and exposed to 0–2 Gy of X-rays, alpha particles or 1:1 mixture of both (half the dose each). DNA damage response was quantified by chromosomal aberrations and by mRNA levels of 3 radiation-responsive genes FDXR, CDKN1A and MDM2 measured 24 h post exposure. The quality of response in terms of differential expression of alternative transcripts was assessed by using two primer pairs per gene. A consistently higher than expected effect of mixed beams was found in both donors for chromosomal aberrations and gene expression with some seasonal variability for the latter. No synergy was detected for alternative transcription.

Comprehensive insights into AML relapse: genetic mutations, clonal evolution, and clinical outcomes.

Acute myeloid leukemia (AML) is a complex hematologic malignancy characterized by uncontrolled proliferation of myeloid precursor cells within bone marrow. Despite advances in understanding of its molecular underpinnings, AML remains a therapeutic challenge due to its high relapse rate and clonal evolution. In this retrospective study, we analyzed data from 24 AML patients diagnosed at a single institution between January 2017 and August 2023. Comprehensive genetic analyses, including chromosomal karyotyping, next-generation sequencing, and gene fusion assays, were performed on bone marrow samples obtained at initial diagnosis and relapse. Clinical data, treatment regimens, and patient outcomes were also documented. Mutations in core genes of FLT3, NPM1, DNMT3A, and IDH2 were frequently discovered in diagnostic sample and remained in relapse sample. FLT3-ITD, TP53, KIT, RUNX1, and WT1 mutation were acquired at relapse in one patient each. Gene fusion assays revealed stable patterns, while chromosomal karyotype analyses indicated a greater diversity of mutations in relapsed patients. Clonal evolution patterns varied, with some cases showing linear or branching evolution and others exhibiting no substantial change in core mutations between diagnosis and relapse. Our study integrates karyotype, gene rearrangements, and gene mutation results to provide a further understanding of AML heterogeneity and evolution. We demonstrate the clinical relevance of specific mutations and clonal evolution patterns, emphasizing the need for personalized therapies and measurable residual disease monitoring in AML management. By bridging the gap between genetics and clinical outcome, we move closer to tailored AML therapies and improved patient prognoses.