Search Results (127)

Background: Genetic alterations in CSF3R, typically associated with chronic neutrophilic leukemia (CNL) and atypical chronic myeloid leukemia (aCML), rarely occur in other myeloid neoplasms. Methods: This study characterized the clinical, morphologic, cytogenetic, and molecular features of 13 patients with non-CNL non-aCML myeloid neoplasms with CSF3R alterations. Patients (median age, 77 years) were categorized into groups with a myelodysplastic/myeloproliferative neoplasm (MDS/MPN) (n = 5), acute leukemia (n = 4), and other myeloid neoplasms (n = 4) based on the WHO 2022 and ICC criteria. Results: The CSF3R p.Thr618Ile mutation was most frequent (11/13), with additional pathogenic variants including p.Gln743Ter and frameshift mutations affecting the cytoplasmic tail. Variant allele frequencies (VAFs) ranged from 2% to 49%, with the highest median VAF in the MDS/MPN group. Co-mutations varied by subtype; MDS/MPN, NOS, and CMML cases frequently harbored mutations in epigenetic regulators (ASXL1, TET2) and splicing factors (SF3B1, SRSF2, ZRSR2), while acute leukemia cases showed alterations in JAK3, STAT3, and NRAS. Survival analysis revealed distinct patterns across the three diagnostic groups, with MDS/MPN having the poorest prognosis. Conclusion: This study expands the recognized spectrum of CSF3R-related myeloid neoplasms and highlights the clinical and molecular heterogeneity associated with these mutations, emphasizing the need for comprehensive molecular profiling and the potential for targeted therapies. Full article

Acute myeloid leukemia (AML), a heterogeneous and aggressive clonal disease, is predominantly observed in older individuals, with a median age at diagnosis of 68–69 years. With the aging population, there is a significant increase in the occurrence of some genetic alterations, including detrimental gene mutations and cytogenetic abnormalities, and a higher incidence of secondary AML (s-AML) and therapy-related AML (t-AML), compared to younger AML patients. Outcomes of AML patients and their response to therapy are associated with the molecular features of AML subtypes and with individual variables. The current criteria for risk classification predict outcomes in younger AML patients treated with intensive chemotherapy but are less predictive for older AML patients treated with lower-intensity treatments. Thus, this review analyzes and discusses the development of new risk stratification models adapted to the study of older AML patients and how these new criteria may significantly contribute to a more rational classification and treatment of older AML patients. Full article

This study aimed to identify genetic variants using a customized next-generation sequencing (NGS) panel for pediatric myelodysplastic syndrome (pMDS) and to explore their associations with cytogenetic and clinical characteristics. Cytogenetic analyses were conducted using G-banding and fluorescence in situ hybridization. NGS was performed with the Ion Torrent Personal Genome Machine for the following genes: GATA2, RUNX1, CEBPA, ANKRD26, ETV6, SAMD9, SAMD9L, PTPN11, NRAS, SETBP1, DDX41, TP53, FLT3, SRP72, and JAK3. Analyses were performed with Ion Reporter 5.20.8.0 software. Genetic variants were classified using the dbSNP, 1000 Genomes, COSMIC, and Varsome databases. We analyzed 25 cases of pMDS; 15 presented abnormal karyotypes, and 19 showed genetic variants. Among the 29 variants identified across 12/15 genes, 27% were pathogenic and 14% were likely pathogenic, with NRAS and GATA2 most frequently associated with disease progression. A new somatic variant of uncertain significance in SETBP1 was detected in seven patients showing heterogeneous clinical outcomes. Genetic variants were found in 7/10 patients with normal karyotypes, indicating that submicroscopic alterations can shed light on disease biology. Our results highlight the critical role of a targeted NGS panel in identifying molecular alterations associated with pMDS pathogenesis, thereby enhancing diagnostic precision, prognosis, and aiding in treatment selection. Full article

Oral cancer, the most common form of head and neck cancer, is worldwide a serious public health problem. Most patients present a locally advanced disease, and face poor prognosis, even with multimodality treatment. They may also develop second primary tumors in the entirety of their upper aerodigestive tract. The most altered signaling pathways are the PI3K/AKT/mTOR, TP53, RB, and the WNT/β-catenin pathways. Genomic and molecular cytogenetic analyses have revealed frequent losses at 3p, 8p, 9p, and 18q, along with gains at 3q, 7p, 8q, and 11q, and several genes frequently affected have been identified, such as TP53, CCND1, CTTN, CDKN2A, EGFR, HRAS, PI3K, ADAM9, MGAM, SIRPB1, and FAT1, among others. Various epigenetic alterations were also found, such as the global hypomethylation and hypermethylation of CDKN2A, APC, MGMT, PTEN, CDH1, TFP12, SOX17, GATA4, ECAD, MGMT, and DAPK. Several microRNAs are upregulated in oral cancer, including miR-21, miR-24, miR-31, miR-184, miR-211, miR-221, and miR-222, while others are downregulated, such as miR-203, miR-100, miR-200, miR-133a, miR-133b, miR-138, and miR-375. The knowledge of this molecular pathogenesis has not yet been translated into clinical practice, apart from the use of cetuximab, an EGFR antibody. Oral tumors are also genetically heterogenous and affect several pathways, which means that, due to the continuous evolution of these genetic alterations, a single biopsy is not sufficient to fully evaluate the most adequate molecular targets when more drugs become available. Liquid biopsies, either resorting to circulating tumor cells, extracellular vesicles or cell-free nucleic acids, have the potential to bypass this problem, and have potential prognostic and staging value. We critically review the current knowledge on the molecular, genetic and epigenetic alterations in oral cancer, as well as the applications and challenges of liquid biopsies in its diagnosis, follow-up, and prognostic stratification. Full article

Plant tissue culture has been recognized as an essential technology in plant science research. This process is widely used to regenerate and conserve phenotypically and genetically identical plant resources. The advancements in tissue culture methods have become a feasible option for the micropropagation of plants at the commercial level. The success of commercial micropropagation necessitates genetic stability among regenerated plants. Sometimes, in vitro-grown plants show genetic and epigenetic alterations due to stressful artificial culture conditions, media compositions, and explant types. As a result, it is essential to ensure genetic stability among tissue culture-derived plantlets at a very early stage. Somaclonal variations can be detected by phenotypic assessment, cytogenetic, DNA-based molecular markers, bisulfite sequencing, and RNA sequencing. This review aims to describe the causes behind somaclonal variation, the selection of somaclonal variants, and their uses in crop and plant improvement at the commercial level. This study discusses the optimization processes of undesirable genetic and epigenetic variation among micropropagated plants and their application in global horticulture, agriculture, and forestry. Full article

Anaplastic Large Cell Lymphoma (ALCL) represents a diverse group of mature T-Cell Lymphomas unified by strong CD30 expression but with different molecular and clinical subtypes. This review summarizes recent molecular advances in ALCL, highlighting key discoveries that have refined its classification, diagnosis, and therapeutic strategies. ALCL comprises four major entities: systemic ALK-positive ALCL, systemic ALK-negative ALCL, Breast Implant-Associated ALCL (BIA-ALCL), and primary cutaneous ALCL. Each subtype exhibits unique phenotypes, along with cytogenetic and molecular alterations that affect clinical outcomes. Nevertheless, different oncogenic mechanisms mediate STAT3 activation. In ALK-positive ALCL, ALK fusion proteins drive oncogenesis via constitutive activation of STAT3 and other signaling pathways. ALK-negative ALCL comprises heterogeneous genetic subtypes, in which JAK/STAT3 pathway alterations and novel gene fusions are gaining recognition as potential therapeutic targets. This review emphasizes the need for integrative molecular diagnostics to improve stratification of ALCL subtypes and targeted treatment approaches. Future research should focus on elucidating the biological mechanisms underlying these alterations and on translating molecular insights into clinical practice. Full article

The biology of Monosomal Karyotype Acute Myeloid Leukemia (MK AML) remains unclear, and its mutational profile has not been exclusively assessed. We sought to determine the genomic profile of MK AML patients and its correlation with overall survival (OS). We conducted a retrospective study involving 664 AML patients, identifying 156 (23.5%) with MK AML. The most common monosomies were -17 (41%) and -7 (37%), with 149 (95%) and 138 (88%) having myelodysplasia-related (MR) cytogenetics and complex karyotype (CK), respectively. Frequent mutations included TP53 (69%), DNMT3A (19%), TET2 (13%), and IDH1 (7%). Patients with MK AML with TP53 mutation (TP53 Mut) had shorter OS compared to those with TP53 wild-type (WT) (median OS, 3.9 versus 9.2 months, p = 0.002). Our validation study further supports this finding. There was no significant difference in OS related to the presence or absence of CK (p = 0.252), MR mutations (p = 0.252), DNMT3A (p = 0.264), TET2 (p = 0.264), and IDH1 (p = 0.183) alterations. Co-mutation with novel EPI6 and TAZI signature alterations did not significantly impact OS among MK AML TP53 Mut patients, suggesting that TP53 Mut remains the dominant driver of outcome in this subgroup. In conclusion, MK AML is a genotypically diverse and high-risk group, with MK AML TP53 Mut indicating worse prognosis. Full article

Optical genome mapping (OGM) is a novel, high-resolution technology for genome-wide detection of structural variants, offering clear advantages over conventional cytogenetics in hematologic malignancies. We applied OGM to a large cohort of patients with acute myeloid leukemia (AML), myelodysplastic syndromes (MDSs), and B-cell acute lymphoblastic leukemia (B-ALL) to evaluate its clinical utility. In AML and MDS, it revealed high-risk alterations such as deletions in 5q31–5q32 and 7q22, and cryptic fusions like NUP98::NSD1 that were missed by karyotyping or FISH. It also identified chromoanagenesis, a catastrophic chromosomal event linked to poor prognosis and often undetectable by standard methods. In B-ALL, OGM uncovered clinically relevant deletions in CDKN2A/B, PAX5, and IKZF1, as well as high-risk ploidy changes like hypodiploidy and hyperdiploidy, all important for risk assessment and frequently underdetected. OGM not only refines diagnosis and improves risk stratification but can also uncover cryptic and complex genomic abnormalities. Our findings support its integration into routine diagnostics to enhance classification, guide treatment decisions, and improve patient outcomes. Full article

The nucleoprotein structures known as telomeres provide genomic integrity by protecting the ends of chromosomes. Tumorigenesis is associated with alterations in telomere function and stability. This narrative review provides evidence of the potential prognostic value of telomere length and telomerase in leukemias. On the one hand, oxidative stress and mitochondrial dysfunction can accelerate telomere shortening, leading to higher susceptibility and the progression of leukemia. On the other hand, cytogenetic alterations (such as gene fusions and chromosomal abnormalities) and genomic complexity can result from checkpoint dysregulation, the induction of the DNA damage response (DDR), and defective repair signaling at telomeres. This review thoroughly outlines the ways by which telomere dysfunction can play a key role in the development and progression of four primary leukemias, including chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML), and acute leukemias of myeloid or lymphoid origin, highlighting the potential prognostic value of telomere length in this field. However, telomerase, which is highly active in leukemias, can prevent the rate of telomere attrition. In line with this, leukemia cells can proliferate, suggesting telomerase as a promising therapeutic target in leukemias. For this reason, telomerase-based immunotherapy is analyzed in the fight against leukemias, leveraging the immune system to eliminate leukemia cells with uncontrolled proliferation. Full article

Artificial intelligence (AI) has entered the medical subspecialty of cytogenetics with the recent introduction of AI-guided karyotyping into the clinical laboratory. Karyotyping is an essential component of the cytogenetic analysis process; however, it is both labor-intensive and time-consuming. The introduction of AI algorithms into karyotyping software streamlines this process to provide accurate and abundant auto-karyotyped images for laboratory professionals to review and, also, alters the paradigm for chromosome analysis. Herein, we provide an overview of the AI-guided karyotyping products currently available for clinical use, discuss their utilization in the cytogenetics laboratory, and highlight changes AI-guided karyotyping has brought for early users. Finally, we reflect on our own laboratory observations and experience to discuss issues and practices that may need to adapt to best utilize this promising new technology. Full article

Background: Cytogenetic abnormalities and the persistence of minimal residual disease (MRD) following autologous stem cell transplantation (ASCT) are two established prognostically unfavorable biomarkers in multiple myeloma (MM). Previous studies have shown that post-transplant MRD status is a powerful predictor of progression-free survival (PFS) and overall survival (OS). However, the impact of MRD remains poorly characterized in MM patients with high- or ultra-high-risk cytogenetics. Objectives: This study investigated the prognostic value of post-transplant MRD in standard- versus high- and ultra-high-risk MM. To this aim, we performed a retrospective analysis of 137 MM patients who underwent high-dose chemotherapy (HDCT) and ASCT at our institution between January 2019 and December 2021. Cytogenetics were assessed by fluorescence in situ hybridization. High-risk genomic alterations included del(17p), t(4;14), t(14;16), t(14;20), gain(1q), and TP53 mutations, with two or more alterations defining the ultra-high-risk category. MRD was assessed in bone marrow aspirates post-ASCT using flow cytometry. Results: Eighty-two (60%) patients were categorized as being at standard risk, forty (29%) as high risk, and fifteen (11%) as ultra-high risk. Median follow-up was 47 months. MRD negativity was achieved in 76 (55%) patients. At 48 months, the overall PFS rate was 61% (72%, 50%, and 32% for the standard-, high-, and ultra-high-risk subgroups, respectively; p = 0.0004), while the OS rate was 85% (89%, 79%, and 80% in standard-, high-, and ultra-high-risk MM patients, respectively; p = 0.1494). Within the standard-risk subgroup, longer PFS was observed for patients achieving MRD negativity (p = 0.0172). High- and ultra-high-risk patients showed no significant differences in PFS when stratified by MRD status, possibly due to prompt progression to MRD positivity. Conclusions: Our results suggest that high- and ultra-high-risk MM patients might benefit from closer response monitoring, including dynamic MRD assessment. Further, high- and ultra-high-risk patients might require a more intensive peri-transplant treatment. Full article

This study presents a comprehensive genetic characterization of the H9c2 cell line, a widely used model for cardiac myoblast research. We established a short tandem repeat (STR) profile for H9c2 that is useful to confirm the identity and stability of the cell line. Additionally, we prepared H9c2 metaphase chromosomes and performed karyotyping and molecular cytogenetics to further investigate chromosomal characteristics. The genetic analysis showed that H9c2 cells exhibit chromosomal instability, which may impact experimental reproducibility and data interpretation. Next-generation sequencing (NGS) was performed to analyze the transcriptome, revealing gene expression patterns relevant to cardiac biology. Western blot analysis further validated the expression levels of selected cardiac genes identified through NGS. Additionally, Phalloidin staining was used to visualize cytoskeletal organization, highlighting the morphological features of these cardiac myoblasts. Our findings collectively support that H9c2 cells are a reliable model for studying cardiac myoblast biology, despite some genetic alterations identified resembling sarcoma cells. The list of genes identified through NGS analysis, coupled with our comprehensive genetic analysis, will serve as a valuable resource for future studies utilizing this cell line in cardiovascular medicine. Full article

Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer, comprising almost 25% of all malignancies diagnosed in children younger than 20 years, and its incidence is still increasing. ALL is a blood cancer arising from the unregulated proliferation of clonal lymphoid progenitor cells. To make a diagnosis of B-cell ALL, bone marrow morphology and immunophenotyping are needed; cerebrospinal fluid examination, and chromosomal analysis are currently used as stratification exams. Currently, almost 70% of children affected by B-cell ALL are characterized by well-known cytogenetic abnormalities. However, the integration of results with “omic” techniques (genomics, transcriptomics, proteomics, and metabolomics, both individually and integrated) able to analyze simultaneously thousands of molecules, has enabled a deeper definition of the molecular scenario of B-cell ALL and the identification of new genetic alterations. Studies based on omics have greatly deepened our knowledge of ALL, expanding the horizon from the traditional morphologic and cytogenetic point of view. In this review, we focus our attention on the “omic” approaches mainly used to improve the understanding and management of B-cell ALL, crucial for the diagnosis, prognosis, and treatment of the disease, offering a pathway toward more precise and personalized therapeutic interventions. Full article

The cell line Sarcoma 180, which is also called S-180 (or S180), was established about 110 years ago from a murine axillary sarcoma. It has been applied in >5000 studies but was never genetically characterized in detail; this study fills that gap. The cell line Sarcoma 180 was analyzed for its chromosomal constitution using molecular cytogenetic approaches, specifically murine multicolor banding (mcb). Additionally, array comparative genomic hybridization was performed to characterize copy number alterations. Sarcoma 180 has a near tetraploid karyotype without Y-chromosome material and only two X-chromosomes. The complex karyotype includes dicentrics and simple and complex rearrangements and shows a relatively high chromosomal instability. An in silico translation of the obtained results to the human genome indicated that Sarcoma 180 is suitable as a model for advanced human mesenchymal chondrosarcoma. Full article

Abdominal wall endometriosis (AWE) is a clinical disorder with unknown pathogenesis with an incidence between 0.03% and 1% in women affected by cutaneous/scar endometriosis. We investigated the pathological, molecular cytogenetic and cell proliferation features of a primary AWE developed in rectus abdominis muscle in a patient without co-existing pelvic endometriosis. An investigational model of cultured stromal cells was additionally established. Histologically, the lesion revealed areas of endometrial-like glands surrounded by a thick stromal layer in addition to numerous disseminated foci composed exclusively of stromal cells. Beyond the strong expression of Estrogen (ER) and Progesterone receptors (PRs), consistent immunolabeling for several mesenchymal stromal/stem cell antigens and oncoproteins was revealed in both the endometrioma as well as in the cultured stromal cells. The Fluorescence in situ hybridization (FISH) analysis of the endometrioma demonstrated a structural alteration of the c-MYC protooncogene, with a mean of three gene copies in 3% to 5% of both glandular and stromal cells. The FISH assay applied on the cultured cells showed c-MYC gene amplification, with an average number of more than six gene copies in 18% to 25% of the cellular nuclei. Altogether, these results markedly highlight the pathological and molecular features of idiopathic AWE essential for histo-pathogenetic categorization. Full article