OBJECTIVE: We explored the feasibility of using total tumor apparent diffusion coefficient (ttADC) histogram parameters to predict high-risk cytogenetic abnormalities (HRCA) in patients with multiple myeloma (MM) and compared the performance of an image prediction model based on these parameters with that of a combined prediction model based on these parameters and clinical indicators.
METHODS: We retrospectively analyzed the parameters of the ttADC histogram based on whole-body diffusion-weighted images(WB-DWI) and clinical indicators in 92 patients with MM. The patients were divided into HRCA and non-HRCA groups according to the results of the fluorescence in situ hybridization. Logistic regression analysis was used to construct the image prediction and combined prediction models. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was used to evaluate the performance of the models to identify HRCA. The DeLong test was used to compare the AUC differences of each prediction model.
RESULTS: Logistic regression analysis results revealed that the ttADC histogram parameter, ttADC entropy < 7.959 (OR: 39.167; 95% confidence interval [CI]: 3.891-394.208; P < 0.05), was an independent risk factor for HRCA. The image prediction model consisted of ttADC entropy and ttADC SD. The combined prediction model included ttADC entropy along with patient clinical indicators such as biological sex and M protein percentage. The AUCs of the image prediction and combined prediction models were 0.739 and 0.811, respectively (P < .05). The image prediction model showed a sensitivity of 73.9% and a specificity of 68.1%. The combined prediction model showed 82.6% sensitivity and 72.5% specificity.
CONCLUSIONS: Using ttADC histogram parameters based on WB-DWI images to predict HRCA in patients with MM is feasible, and combining ttADC parameters with clinical indicators can achieve better predictive performance.

(1) Background: The introduction of novel therapies has led to a considerable evolution in the management of Multiple Myeloma, and chromosomal abnormalities predict the success of treatment. We aimed to characterize cytogenetic abnormalities for risk stratification in the patient population and to evaluate the predictive and prognostic value of the specified abnormalities in distinct treatment modalities. (2) Methods: This study included patients with Multiple Myeloma who applied to the Internal Medicine Clinic of the Cukurova University Faculty of Medicine. Between 2010 and 2023, 98 cases with cytogenetic abnormality data were identified. We analysed the effects of cytogenetic abnormalities on survival and response rates to first chemotherapies. (3) Results: P53 del was the most prevalent abnormality, and t(11;14) was the most common translocation. There was no significant difference in the mean survival and treatment response rates for specific cytogenetic abnormalities. When chemotherapies based on lenalidomide were initiated, patients\' life-death statuses differed significantly from those of treatments without lenalidomide. Regardless of the type of chromosomal aberration, lenalidomide-based treatments independently enhanced average survival 14-fold, while there was no significant difference in overall survival among treatments. (4) Conclusions: In individuals with cytogenetic abnormalities, lenalidomide-based treatments should be started regardless of the chemotherapy to be used for the condition.

The potential prognostic influence of genetic aberrations on chronic lymphocytic leukaemia (CLL) can vary based on various factors, such as the immunoglobulin heavy variable (IGHV) status. We conducted an integrative analysis on genetic abnormalities identified through cytogenetics and targeted next-generation sequencing in 536 CLL patients receiving first-line chemo(immuno)therapies (CIT) as part of two prospective trials. We evaluated the prognostic implications of the main abnormalities, with specific attention to their relative impact according to IGHV status. In the entire cohort, unmutated (UM)-IGHV, complex karyotype, del(11q) and ATM mutations correlated significantly with shorter progression-free survival (PFS). Focusing on the subset of mutated IGHV (M-IGHV) patients, univariate analysis showed that complex karyotype, del(11q), SF3B1 and SAMHD1 mutations were associated with significant lower PFS. The prognostic influence varied based on the patient\'s IGHV status, as these abnormalities did not affect outcomes in the UM-IGHV subgroup. TP53 mutations had no significant impact on outcomes in the M-IGHV subgroup. Our findings highlight the diverse prognostic influence of genetic aberrations depending on the IGHV status in symptomatic CLL patients receiving first-line CIT. The prognosis of gene mutations and cytogenetic abnormalities needs to be investigated with a compartmentalized methodology, taking into account the IGVH status of patients receiving first-line BTK and/or BCL2 inhibitors.

Lam et al. compared trisomy acute myeloid leukaemia (AML) patients (inclusive of single trisomy, double trisomy or tetrasomy cases) with cytogenetically normal AML to uncover distinguishing molecular and prognostic features of trisomy AML. The study contributes to our understanding of trisomy AML, but the heterogeneity of trisomy subtypes remains a barrier to its study. Commentary on: Lam et al. Distinct karyotypic and mutational landscape in trisomy AML. Br J Haematol 2024;204:939-944.

Genetic data are becoming increasingly essential in the management of hematological neoplasms as shown by two classifications published in 2022: the 5th edition of the World Health Organization Classification of Hematolymphoid Tumours and the International Consensus Classification of Myeloid Neoplasms and Acute Leukemias. Genetic data are particularly important for acute myeloid leukemias (AMLs) because their boundaries with myelodysplastic neoplasms seem to be gradually blurring. The first objective of this review is to present the latest updates on the most common cytogenetic abnormalities in AMLs while highlighting the pitfalls and difficulties that can be encountered in the event of cryptic or difficult-to-detect karyotype abnormalities. The second objective is to enhance the role of cytogenetics among all the new technologies available in 2023 for the diagnosis and management of AML.

The number of predisposing genes is continuously growing with the widespread availability of DNA sequencing, increasing the prevalence of hematologic malignancies with germline predisposition. Cytogenetic analyses provide an effective approach for the recognition of these malignancies with germline predisposition, which is critical for proper diagnosis, optimal treatment and genetic counseling. Based on the World Health Organization and the international consensus classifications as well as the European LeukemiaNet recommendations, this review first presents an advanced classification of neoplasms with germline predisposition focused on the acquired cytogenetic alterations during leukemogenesis. The various genetic rescue mechanisms and the progression to transformation are then explained. The review also outlines the specific constitutional and somatic cytogenetic aberrations indicative of germline predisposition disorders in B-acute lymphoblastic leukemia (ALL), T-ALL, bone marrow failure syndrome and myeloid neoplasms. An emphasis is made on monosomy 7 in the predisposition field, its frequency and diagnosis impact as well as its various circumstances of occurrence. Lastly, we propose cytogenetic technical recommendations and guidelines for clinical reporting of these specific aberrations.

Acute myeloid leukemia (AML) is an aggressive hematopoietic malignancy with several patient- and disease-associated variables known to impact prognosis. Tobacco smoking is an environmental factor associated with a greater incidence of AML, but there have been limited studies that evaluated smoking toward overall survival. We retrospectively searched for AML cases and collected clinical and diagnostic data for each case. We also used an independent next-generation sequencing (NGS) data set to assess for a distinct mutational signature associated with smoking. When stratified by smoking status, there was a greater number of males, patients aged ≥60 years, and patients with ≥2 comorbidities within the smoking category (P < .05). Survival analysis demonstrated decreased survival probability in the smokers, male smokers, smokers with 1 other comorbidity, and smokers without a prior history of nonhematopoietic malignancy (P < .05) as compared to nonsmokers. Smoking was associated with a decrease in survival within the World Health Organization categories of AML, not otherwise specified (AML NOS; P = .035) and AML with recurrent genetic abnormalities (AML RGA; P = .002). Multivariate analysis showed that patients who were smokers had a greater hazard ratio than nonsmokers after adjusting for the other covariates. Our findings demonstrated that smoking was independently associated with decreased overall survival after adjusting for other potentially confounding factors. In addition, our results suggest that a mutational signature can be recognized using NGS data in a subset of AML patients who smoke.

BACKGROUND: Forty-six ,XY Differences/Disorders of Sex Development (DSD) are characterized by a broad phenotypic spectrum ranging from typical female to male with undervirilized external genitalia, or more rarely testicular regression with a typical male phenotype. Despite progress in the genetic diagnosis of DSD, most 46,XY DSD cases remain idiopathic.
METHODS: To determine the genetic causes of 46,XY DSD, we studied 165 patients of Tunisian ancestry, who presented a wide range of DSD phenotypes. Karyotyping, candidate gene sequencing, and whole-exome sequencing (WES) were performed.
RESULTS: Cytogenetic abnormalities, including a high frequency of sex chromosomal anomalies (85.4%), explained the phenotype in 30.9% (51/165) of the cohort. Sanger sequencing of candidate genes identified a novel pathogenic variant in the SRY gene in a patient with 46,XY gonadal dysgenesis. An exome screen of a sub-group of 44 patients with 46,XY DSD revealed pathogenic or likely pathogenic variants in 38.6% (17/44) of patients.
CONCLUSIONS: Rare or novel pathogenic variants were identified in the AR, SRD5A2, ZNRF3, SOX8, SOX9 and HHAT genes. Overall our data indicate a genetic diagnosis rate of 41.2% (68/165) in the group of 46,XY DSD.

OBJECTIVE: To elucidate the clinical characteristics of AA patients with cytogenetic abnormalities.
METHODS: We retrospectively screened 30 patients (30/1206, 2.5%) with cytogenetic abnormalities from 1206 patients with severe and very severe AA who received immunosuppressive therapy (IST) during the years 2012-2019.
RESULTS: The most common abnormalities were trisomy 8 (+8, 10/30, 33.3%) and loss of Y (-Y, 8/30, 26.7%). The abnormal clones disappeared 6 months after IST in 14 patients and sustained in 12 patients. Patients with sustained abnormal clones had a lower hematologic response at 6 months after IST than the disappeared (33.3% vs. 64.3%, p = .116). The hematologic response after IST, 5-year overall survival, 5-year event-free survival, myelodysplastic syndrome or acute myeloid leukemia transformation in AA patients with cytogenetic abnormalities were not statistically different from those in normal cytogenetic patients.
CONCLUSIONS: For AA patients with chromosome abnormalities but ineligible for hematopoietic stem cell transplant, IST is effective and appropriate as first-line treatment.

UNASSIGNED: Acute lymphoid leukemia (ALL) is the largest subset of hematologic malignancies, accounting for approximately 70%-80% of childhood leukemia, and is most common at age 4 years. The aim of this study was to define the frequency of chromosomal abnormalities in pediatric ALL.
UNASSIGNED: In this 11-year retrospective study, we investigated 99 patients which referred to our department due to ALL from 2010 to 2020. The age group of the patients ranged from 6 months to 14 years with a mean of 6.71 ± 4.09 years. Clinical and diagnostic findings were extracted from patients\' medical records.
UNASSIGNED: We showed cytogenetic abnormalities of 99 pediatric ALL patients, including 78 pre-B-ALL, 9 common B-ALL, and 12 T-ALL cases. The 5-year overall survival rate (OSR) and event-free survival (EFS) of all cytogenetic abnormalities (n = 99) were 48% and 43%, respectively. There was a significant relationship between the two cytogenetic abnormalities, hypodiploidy and t(9;22), with death (P < 0.05). On comparing the subjects with normal cytogenetics to the other cytogenetic abnormalities, EFS was significantly low for hypodiploidy (P = 0.0163, hazard ratio = 0.5308) and t(9;22) (P = 0.0131, hazard ratio = 0.4908), while other cytogenetic abnormalities did not have a statistically significant difference in EFS.
UNASSIGNED: Our results emphasized the importance of the cytogenetic findings in evaluating the survival outcomes, which allows identifying a variety of OSR and EFS, because some of the cytogenetic abnormalities may interfere with the death and prognosis.