Optical genome mapping improves the accuracy of classification, risk stratification, and personalized treatment strategies for patients with acute myeloid leukemia.

Cytogenomic characterization is crucial for the classification and risk stratification of acute myeloid leukemia (AML), thereby facilitating therapeutic decision-making. We examined the clinical utility of optical genome mapping (OGM) in 159 AML patients (103 newly diagnosed and 56 refractory/relapsed), all of whom also underwent chromosomal banding analysis (CBA), fluorescence in situ hybridization, and targeted next-generation sequencing. OGM detected nearly all clinically relevant cytogenetic abnormalities that SCG identified with >99% sensitivity, provided the clonal burden was above 20%. OGM identified additional cytogenomic aberrations and/or provided information on fusion genes in 77 (48%) patients, including eight patients with normal karyotypes and four with failed karyotyping. The most common additional alterations identified by OGM included chromoanagenesis (n = 23), KMT2A partial tandem duplication (n = 11), rearrangements involving MECOM (n = 7), NUP98 (n = 2), KMT2A (n = 2), JAK2 (n = 2), and other gene fusions in 17 patients, with 10 showing novel fusion gene partners. OGM also pinpointed fusion genes in 17 (11%) patients where chromosomal rearrangements were concurrently detected by OGM and CBA. Overall, 24 (15%) aberrations were identified exclusively by OGM and had the potential to alter AML classification, risk stratification, and/or clinical trial eligibility. OGM emerges as a powerful tool for identifying fusion genes and detecting subtle or cryptic cytogenomic aberrations that may otherwise remain undetectable by CBA.

Primary mediastinal germ cell tumor and clonally related and unique hematologic neoplasms with i(12p) and TP53 mutation: A report of two cases.

The development of clonally related hematologic neoplasms in the setting of primary mediastinal germ cell tumors (PMGCTs) has been recognized previously and is associated with a dismal prognosis. However, the presentation of hematologic neoplasms as chronic myelomonocytic leukemia (CMML) and hemophagocytic lymphohistiocytosis (HLH) has been rarely reported. Here we report two patients with PMGCTs and hematologic neoplasms. The PMGCT was composed mostly of yolk sac tumor whereas the hematologic neoplasms had morphologic features that resembled CMML and HLH. The hematologic neoplasms from both patients harbored isochromosome 12p [i(12p)] and TP53 mutations, supporting a clonal relationship between these tumors. This association represents a unique clinical syndrome that likely contributes to the poor clinical outcome of these patients.

Critical care for lung cancer patients: surgical treatment during COVID-19 pandemic.

BACKGROUND: During the COVID-19 pandemic, some factors have led to changes in the management of patients with lung cancer. In our study, we aimed to present our surgical treatment approach to patients with NSCLC during the COVID-19 pandemic. METHODS: Patients who underwent surgery for NSCLC in our thoracic surgery clinic between March 2020 and March 2021 were evaluated retrospectively. The patients operated on were retrospectively evaluated in terms of sex, age, tumor staging, lung resection type, histopathological type, COVID-19 status, length of stay, complications, and mortality. RESULTS: Thirty-five patients, 27 men and 8 women, underwent surgery for lung cancer. The 2 most common types of surgery were lobectomy (in 32 patients) and pneumonectomy (in 3 patients). According to cancer staging based on 8th TNM, 14 patients were stage 2B, 12 patients were stage 2A, and 9 patients were stage 3A. The morbidity rate was 14 %. No postoperative mortality was observed. Nine patients had a history of COVID- 19 before surgery. No significant difference was found in terms of complications in patients with a preoperative history of COVID-19. In the postoperative period, COVID-19 was observed in no patient in our clinic. CONCLUSION: We think that surgical treatments should not be postponed for diseases such as lung cancer, where the mortality rate is high and early diagnosis and treatment are very important. There will be no delay or inadequacy in the treatment of patients if the rules determined during the COVID-19 pandemic and other types of pandemic possibly occurring in the future are followed (Tab. 1, Ref. 23).

Chronic myeloid leukemia with insertion-derived BCR-ABL1 fusion: redefining complex chromosomal abnormalities by correlation of FISH and karyotype predicts prognosis.

Chromosomal insertion-derived BCR-ABL1 fusion is rare and mostly cryptic in chronic myeloid leukemia (CML). Most of these cases present a normal karyotype, and their risk and/or prognostic category are uncertain. We searched our database and identified 41 CML patients (20 M/21 F, median age: 47 years, range 12-78 years) with insertion-derived BCR-ABL1 confirmed by various FISH techniques: 31 in chronic phase, 1 in accelerated phase, and 9 in blast phase at time of diagnosis. Conventional cytogenetics analysis showed a normal karyotype (n = 19); abnormal karyotype with morphologically normal chromosomes 9 and 22 (n = 5); apparent ins(9;22) (n = 2) and abnormal karyotype with apparent abnormal chromosomes 9, der(9) and/or 22, der(22) (n = 15). The locations of insertion-derived BCR-ABL1 were identified on chromosome 22 (68.3%), 9 (29.3%), and 19 (2.4%). Complex chromosomal abnormalities were often overlooked by conventional cytogenetics but identified by FISH tests in many cases. After a median follow-up of 58 months (range 1-242 months), 11 patients died, and 3 lost contact, while the others achieved different cytogenetic/molecular responses. The locations of BCR-ABL1 (der(22) vs. non-der(22)) and the karyotype results (complex karyotype vs. noncomplex karyotype) by conventional cytogenetics were not associated with overall survival in this cohort. However, redefining the complexity of chromosomal abnormality by correlating karyotype and FISH findings, CML cases with simple chromosomal abnormalities had a more favorable overall survival than that with complex chromosomal abnormalities. We conclude that insertion-derived BCR-ABL1 fusions often involve complex chromosomal abnormalities which are overlooked by conventional cytogenetics, but can be identified by one or more FISH tests. We also suggest that the traditional cytogenetic response criteria may not apply in these patients, and the complexity of chromosomal abnormalities redefined by correlating karyotype and FISH findings can plays a role in stratifying patients into more suitable risk groups for predicting prognosis. (Word count: 292).

Correction: Chronic myeloid leukemia with insertion-derived BCR-ABL1 fusion: redefining complex chromosomal abnormalities by correlation of FISH and karyotype predicts prognosis.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Surgical outcomes of sleeve resections performed for non-small cell lung cancer; A single center experience.

BACKGROUND: Although bronchial sleeve resections were performed instead of pneumonectomy in patients with insufficient pulmonary function initially, it is currently available as an alternative to pneumonectomy even in patients with adequate pulmonary reserve. AIMS: In this study, we aimed to evaluate the sleeve resections performed for lung cancer in terms of technical, postoperative complication mortality, survival rates and survival factors, complication and to compare them with the literature. METHODS: Patients who underwent sleeve lung resection with diagnosis of non-small cell lung cancer at our department between January 2012 and December 2017 were included in the study. Patients' data were analyzed according to tumor size, tumor histopathology, hilar/mediastinal lymph nodes invasion status, postoperative complications, operative mortality, resection type, overall survival and diseases-free survival, tumor location, and length of stay in intensive care unit. RESULTS: A total of 71 patients included the study. Right upper sleeve lobectomy was applied to 40 (56.3%) patients and left upper sleeve lobectomy was performed to 19 (26.8%) patients. The most common histopathological diagnosis was squamous cell carcinoma. The mean tumor diameter was 3.39 (SD: 2.25) cm. There was no nodal invasion in 41 (57.7%) patients and N1 nodal positivity was detected in 18 (25.4%) patients and N2 positivity in 12 (16.9%) patients. Median survival time was 43.6 months (35.4-51.8 months), the 3- and 5-year overall survival were 65.7% and 40.6%, respectively. There was a statistically significant correlation relationship between nodal invasion and recurrence, but this relation was not found in overall survival. CONCLUSION: In our study, no significant correlation was found between mediastinal lymph node invasion and overall survival. Supporting this result with multi-centered and prospective studies may encourage surgeons for sleeve resection in indicated patients had lung cancer with nodal invasion.

Effects of thoracic epidural or intravenous analgesia on the neutrophil-to-lymphocyte ratio in thoracotomy cases.

BACKGROUND AND PURPOSE: Postoperative pain is a significant problem in thoracotomy patients. Our aim in this study was to investigate the relationship between postoperative pain and neutrophil-to-lymphocyte ratio (NLR) which is a marker of acute inflammatory response. MATERIALS AND METHODS: Thoracic epidural or intravenous analgesia was administered to thoracotomy patients who elected to undergo a planned surgery. Patients were divided into two groups according to the analgesia method applied postoperatively. Thoracic epidural analgesia was recorded as Group 1 and intravenous analgesia as Group 2. Whole blood counts were recorded from preoperative and postoperative 24th- and 48th-hour routine blood samples, and NLRs were recorded as retrospective file scanning. Postoperative 24th- and 48th-hour NLRs and preoperative NLR values were recorded. RESULTS: Demographic data of the patients included in the study were similar except for age. Preoperative NLR was significantly higher in Group 1 at 3.50 (P = 0.004) than in Group 2 at 2.51. Postoperative NLRs were similar among both groups. Postoperative NLR values at both the 24th- and 48th-hour increased by4.9 times in Group 1 and 9.23 times in Group 2 from the 24th-hour preoperative period, when the preoperative NLRs were evaluated. The rate of increase in Group 1 was significantly lower than in Group 2 (P = 0.006). CONCLUSION: Postoperative NLR alterations when compared with preoperative values were related to the analgesic regimen used.

MicroRNA expression changes in association with changes in interleukin-1ß/interleukin10 ratios produced by monocytes in autism spectrum disorders: their association with neuropsychiatric symptoms and comorbid conditions (observational study).

BACKGROUND: MicroRNAs (miRNAs) play a major role in regulating immune responses at post-transcriptional levels. Previously, we have reported fluctuating interlukine-1ß (IL-1ß)/IL-10 ratios produced by peripheral blood monocytes (PBMo) in some patients with autism spectrum disorders (ASD). This study examined whether changes in miRNA expression by PBMo are associated with changes in IL-1ß/IL-10 ratios and how such changes are associated with ASD clinical features. METHODS: miRNA expression by purified PBMo from ASD subjects (N = 69) and non-ASD controls (N = 27) were determined by high-throughput sequencing. Cytokine production by PBMo in responses to stimuli of innate immunity, and behavioral symptoms [assessed by aberrant behavioral checklist (ABC)] were also evaluated at the same time of sample obtainment. RESULTS: As a whole, there was no difference in miRNA expression between ASD and control non-ASD PBMo. However, when ASD cells were subdivided into 3 groups with high, normal, or low IL-1ß/IL-10 ratios as defined in the "Results" section, in comparison with the data obtained from non-ASD controls, we observed marked changes in miRNA expression. Namely, over 3-fold changes in expression of miR-181a, miR-93, miR-223, miR-342, and miR-1248 were observed in ASD PBMo with high or low IL-1ß/IL-10 ratios, but not in ASD PBMo with normal ratios. These miRNAs that had altered in expression are those closely associated with the regulation of key signaling pathways. With changes in IL-1ß/IL-10 ratios, we also observed changes in the production of cytokines (IL-6, TNF-α, and TGF-ß) other than IL-1ß/IL-10 by ASD PBMo. The association between behavioral symptoms and cytokine levels was different when ASD cells exhibit high/low IL-1ß/IL-10 ratios vs. when ASD cells exhibited normal ratios. Non-IgE-mediated food allergy was also observed at higher frequency in ASD subjects with high/low IL-1ß/IL-10 ratios than with normal ratios. CONCLUSIONS: Changes in cytokine profiles and miRNA expression by PBMo appear to be associated with changes in ASD behavioral symptoms. miRNAs that are altered in expression in ASD PBMo with high/low IL-1ß/IL-10 ratios are those associated with inflammatory responses. Changes in IL-1ß/IL-10 ratios along with changes in miRNA expression may serve as biomarkers for immune-mediated inflammation in ASD.

Changes in retinal vessels related to varicocele: a pilot investigation.

The aim of this study was to investigate whether retinal vasculature changes had occurred (retinal artery diameter, retinal vein diameter and artery/vein ratio) in patients with varicocele. This pilot study included 50 healthy subjects with any eye disease apart from slight refractive errors and 55 patients with varicocele. Retinal arteriolar and venular diameters were measured and summarised as central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE). Retinal microvascular diameters and the arteriolar-to-venular ratio (AVR) were assessed with a digital retinal camera. All measurements and calculations were performed using a computer-based program. The mean CRAE value was 151.8 ± 3.6 µm in the study group and 150.4 ± 4.5 µm in the control group. Mean CRVE value was 209.4 ± 5.9 µm in the study group and 200.1 ± 8.7 µm in the control group. AVR was found 0.72 ± 0.02 in the study group and 0.75 ± 0.03 in the control group. There were significant differences between groups in terms of CRVE and AVR. There were no significant differences between groups in terms of CRAE. The results of this study showed that the patients with varicocele showed significant changes on retinal vascular diameter.

Detection of clinically actionable gene fusions by next-generation sequencing-based RNA sequencing of non-small cell lung cancer cytology specimens: A single-center experience with comparison to fluorescence in situ hybridization.

BACKGROUND: Genomic profiling is needed to identify actionable alterations in non-small cell lung cancer (NSCLC). Panel-based testing such as next-generation sequencing (NGS) is often preferred to interrogate multiple alterations simultaneously. In this study, we evaluate the utility of an RNA-based NGS assay to detect genomic alterations in NSCLC cytology specimens and compare these results to fluorescence in situ hybridization (FISH) testing. METHODS: A retrospective review was performed of 264 NSCLC cytology specimens that were concurrently tested for gene fusions by RNA-based NGS and ALK, RET, and/or ROS1 by FISH. RESULTS: Genomic alterations were detected in 29 cases by NGS, including ALK, RET, ROS1, NTRK, NUTM1, and FGFR3 fusions and MET exon 14 skipping alterations. Of the 20 cases with ALK, RET, and ROS1 fusions detected by NGS, 16 (80%) were concordant with the corresponding FISH results. Three cases showed discordance, where EML4::ALK (n = 2) and SLC34A2::ROS1 (n = 1) fusions were not detected by the corresponding FISH assay; one case with EZR::ROS1 was inadequate for FISH. No gene fusions were detected in 181 cases by NGS and 54 cases failed testing. The concordance rates for detecting ALK, RET, and ROS1 fusions using NGS and FISH were 97%, 100%, and 99.5%, respectively. CONCLUSION: RNA-based NGS can be used to detect gene fusions in NSCLC cytology cases with high concordance with FISH results. However, RNA-based NGS may have high failure rates and therefore a low threshold for reflexing inadequate cases to an orthogonal testing method is essential for comprehensive genomic profiling.

Optical genomic mapping is a helpful tool for detecting CCND1 rearrangements in CD5-negative small B-cell lymphoma: Two cases of leukemic non-nodal mantle cell lymphoma.

Optical genome mapping (OGM) is a new DNA-based technology which provides comprehensive examination of the entire genome. We report two patients who presented with splenomegaly and leukocytosis with lymphocytosis including villous lymphocytes. Neither patient had lymphadenopathy. Bone marrow evaluation showed involvement by small B-cell lymphoma in a sinusoidal and interstitial distribution, and immunophenotypic analysis showed that the neoplastic cells were positive for B-cell markers and cyclin D1 but were negative for SOX11 and CD5. Initially, the clinicopathologic features in both patients were thought to be suspicious for hairy cell leukemia variant or splenic marginal zone lymphoma. However, OGM detected CCND1 rearrangement: t(2;11)/IGK::CCND1 in one case and t(11;14)/IGH::CCND1 in the other case. These cases illustrate the valuable role OGM can play in establishing the diagnosis of MCL. Case 1 also contributes to the paucity of literature on the rare occurrence of IGK::CCND1 in MCL.

A lactotransferrin single nucleotide polymorphism demonstrates biological activity that can reduce susceptibility to caries.

Streptococcus mutans is prominently linked to dental caries. Saliva's influence on caries is incompletely understood. Our goal was to identify a salivary protein with anti-S. mutans activity, characterize its genotype, and determine genotypic variants associated with S. mutans activity and reduced caries. An S. mutans affinity column was used to isolate active moieties from saliva obtained from a subject with minimal caries. The bound and eluted protein was identified as lactotransferrin (LTF) by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) analysis and confirmed by Western blotting with LTF antibody. A single nucleotide polymorphism (SNP) that produced a shift from arginine (R) to lysine (K) at amino acid position 47 in the LTF antimicrobial region (rs: 1126478) killed S. mutans in vitro. Saliva from a subject with moderate caries and with the LTF "wild-type" R form at position 47 had no such activity. A pilot genetic study (n = 30) showed that KK subjects were more likely to have anti-S. mutans activity than RR subjects (P = 0.001; relative risk = 3.6; 95% confidence interval [95% CI] = 1.5 to 11.13). Pretreatment of KK saliva with antibody to LTF reduced S. mutans killing in a dose-dependent manner (P = 0.02). KK subjects were less likely to have caries (P = 0.02). A synthetic 11-mer LTF/K peptide killed S. mutans and other caries-related bacteria, while the LTF/R peptide had no effect (P = 0.01). Our results provide functional evidence that the LTF/K variant results in both anti-S. mutans activity and reduced decay. We suggest that the LTF/K variant can influence oral microbial ecology in general and caries-provoking microbes specifically.

PDE5 inhibitors: considerations for preference and long-term adherence.

INTRODUCTION: Erectile dysfunction (ED) is a highly prevalent condition affecting nearly one in five men worldwide. The advent of phosphodiesterase type 5 inhibitors (PDE5i) has revolutionised the ED treatment landscape and provided effective, minimally invasive therapies to restore male sexual function. MATERIALS AND METHODS: A pubmed search was performed of all English language articles from 1996 to present reviewing PDE5i, including pharmacokinetics, efficacy profiles and comparisons, where available. RESULTS: Currently available PDE5i in the United States include sildenafil, vardenafil, tadalafil and avanafil, each of which has unique side effect, pharmacokinetic and outcome profiles. Sildenafil is associated with increased rate of visual changes, vardenafil with QT prolongation and tadalafil with lower back pain. Avanafil and vardenafil orodispersible tablet rapidly achieve peak plasma concentration, which results in faster onset of action, whereas tadalafil exhibits the longest half-life. First time response to PDE5i is approximately 60-70%, with no significant differences in efficacy noted among therapies. The literature does not clearly demonstrate a preference for one drug. High-treatment success rates (89%) were reported when patients were prescribed all available PDE5i. Daily dosing with tadalafil is associated with improved erectile function (EF) over time. Finally, novel modes of patient-provider interaction, including internet-based education, communication and prescribing, may also improve long-term adherence. CONCLUSIONS: PDE5i represent first line therapy for ED with excellent overall efficacy and satisfactory side effect profiles. Enhanced communciation, coupled with increased knowledge of drug characteristics, comparative treatment regimens and optimal prescribing patterns, offer compelling tools to improve long-term treatment success.

Clinical impact of 5'MYC or 3'MYC gain/loss detected by FISH in patients with aggressive B-cell lymphomas.

FISH analysis using MYC break-apart probes is a widely used technique to assess for MYC rearrangement (MYC-R). Occasionally, FISH results in atypical signal patterns, such as gain or loss of 5'MYC or 3'MYC. The clinical impact and/or relationship of these atypical signal patterns to MYC-R are unknown. In this study, we assessed 35 patients who had aggressive B-cell lymphomas and exhibited atypical FISH signal patterns: 3'MYC deletion (n = 16) or 3'MYC deletion plus 5'MYC amplification (n = 5), 5'MYC gain (n = 10), 5'MYC deletion (n = 3), and 3'MYC gain (n = 1). For comparison, we also included 9 patients who showed an unbalanced MYC-R. Patients with 5'MYC gain showed MYC expression and were often refractory to chemotherapy (n = 7) or had early relapse (n = 2). By contrast, lymphomas with 3'MYC deletion were negative or had low expression of MYC (16 of 18), and patients often responded to chemotherapy (16 of 19). The median event-free survival was 24, 6, and 4 months for patients with 3'MYC deletion, 5'MYC gain and unbalanced MYC-R, respectively (p = 0.0048). We conclude that 5'MYC gain is associated with MYC expression and a poorer prognosis and likely represents an unbalanced MYC-R. By contrast, 3'MYC deletions are not associated with MYC expression or a poorer prognosis and this finding may be unrelated to MYC-R.

Recurrent Somatic Copy Number Alterations and Their Association with Oncogene Expression Levels in High-Grade Ovarian Serous Carcinoma.

Somatic copy number alterations (SCNAs) are frequently observed in high-grade ovarian serous carcinoma (HGOSC). However, their impact on gene expression levels has not been systematically assessed. In this study, we explored the relationship between recurrent SCNA and gene expression using The Cancer Genome Atlas Pan Cancer dataset (OSC, TCGA, PanCancer Atlas) to identify cancer-related genes in HGOSC. We then investigated any association between highly correlated cancer genes and clinicopathological parameters, including age of diagnosis, disease stage, overall survival (OS), and progression-free survival (PFS). A total of 772 genes with recurrent SCNAs were observed. SCNA and mRNA expression levels were highly correlated for 274 genes; 24 genes were classified as a Tier 1 gene in the Cancer Gene Census in the Catalogue of Somatic Mutations in Cancer (CGC-COSMIC). Of these, 11 Tier 1 genes had highly correlated SCNA and mRNA expression levels: TBL1XR1, PIK3CA, UBR5, EIF3E, RAD21, EXT1, RECQL4, KRAS, PRKACA, BRD4, and TPM4. There was no association between gene amplification and disease stage or PFS. EIF3E, RAD21, and EXT1 were more frequently amplified in younger patients, specifically those under the age of 55 years. Patients with tumors carrying PRKACA, BRD4, or TPM4 amplification were associated with a significantly shorter OS. RECQL4 amplification was more frequent in younger patients, and tumors with this amplification were associated with a significantly better OS.

Optical Genome Mapping Helps to Identify BCR::JAK2 Rearrangement Arising from Cryptic Complex Chromosomal Aberrations: A Case Report and Literature Review.

We report a case of myeloproliferative neoplasm, not otherwise specified (MPN-NOS)-transformed AML with BCR::JAK2 rearrangement. Chromosomal analysis indicated a simple abnormal karyotype 46,XY,t(7;17)(q21;q24),t(9;22)(p24;q11.2). Fluorescence in situ hybridization (FISH) using a BCR/ABL1/ASS1 probe set suggested a possible BCR rearrangement and a reflex JAK2 breakapart probe indicated JAK2 rearrangement, most likely partnered with BCR. Optical genome mapping (OGM) analysis confirmed BCR::JAK2 derived through an inv(9)(p24p13) after a t(9;22)(p13;q11.2) in this case. Due to the complexity of chromosomal aberrations, disruption and/or rearrangement of other genes such as KIF24::BCR, JAK2::KIF24/UBAP1, and CDK6:SOX9 were also identified by OGM. Although the functionality and clinical importance of these novel rearrangements were unknown, disruption of these genes might be associated with a poorer response to chemotherapy and disease progression. We also reviewed all cases with BCR::JAK2 rearrangement reported in the literature. In conclusion, a suspected t(9;22)/BCR::JAK2 rearrangement warrants further characterization with genomic assays such as OGM, whole chromosome sequencing, and RNA sequencing to explore other gene disruptions and/or rearrangements.

Cytogenetic Profile in Monoclonal Gammopathy of Undetermined Significance, Smoldering and Symptomatic Multiple Myeloma: A Study of 1087 Patients with Highly Purified Plasma Cells.

The aim of this study was to examine the cytogenetic profiles of plasma cell neoplasms (PCNs) at various disease stages, encompassing 1087 patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), newly diagnosed multiple myeloma (NDMM), and refractory/relapsed multiple myeloma (RRMM). Fluorescence in situ hybridization (FISH) analyses were conducted on highly purified plasma cell samples, revealing that 96% of patients exhibited at least one cytogenetic abnormality. The genomic complexity escalated from MGUS to SMM and further to NDMM and RRMM, largely driven by 1q gain, del(17p), MYC-rearrangement (MYC-R), del(1p), and tetraploidy. Elevated frequencies of high-risk cytogenetics (59%), 1q gain (44%), and del(17p) (23%), as well as the presence of subclones (48%), were particularly notable in RRMM cases. IGH::CCND1 was observed in 26% of the cases, with no apparent variations across races, ages, or disease groups. Concurrent chromosomal analysis with FISH revealed that the incidence of abnormal karyotypes was strongly correlated with the extent of neoplastic plasma cell infiltration, genomic complexity, and the presence of specific abnormalities like del(17p) and MYC-R. Approximately 98% of the cases with abnormal karyotypes were complex, with most featuring five or more abnormalities. Chromosome 1 structural abnormalities were the most prevalent, found in 65% of cases. The frequent presence of subclones and composite karyotypes underscored the genomic heterogeneity and instability in this cohort.