Cytogenomic description of a Mexican cohort with differences in sex development.

BACKGROUND: Differences in Sex Development (DSD) is a heterogeneous group of congenital alterations that affect inner and/or outer primary sex characters. Although these conditions do not represent a mortality risk, they can have a severe psycho-emotional impact if not appropriately managed. The genetic changes that can give rise to DSD are diverse, from chromosomal alterations to single base variants involved in the sexual development network. Epidemiological studies about DSD indicate a global frequency of 1:4500-5500, which can increase to 1:200-300, including isolated anatomical defects. To our knowledge, this study is the first to describe epidemiological and genetic features of DSD in a cohort of Mexican patients of a third-level care hospital. METHODS: Descriptive and retrospective cross-sectional study that analyzed DSD patients from 2015 to 2021 attended a Paediatric Hospital from Mexico City. RESULTS: One hundred one patients diagnosed with DSD were registered and grouped into different entities according to the Chicago consensus statement and the diagnosis defined by the multidisciplinary group. Of the total, 54% of them belong to the chromosomal DSD classification, 16% belongs to 46, XX and 30% of them belongs to the 46, XY classification. CONCLUSION: The frequency for chromosomal DSDs was consistent with the literature; however, we found that DSD 46, XY is more frequent in our cohort, which may be due to the age of the patients captured, the characteristics of our study population, or other causes that depend on the sample size.

Radiomic nomogram for predicting high-risk cytogenetic status in multiple myeloma based on fat-suppressed T2-weighted magnetic resonance imaging.

Rationale and Objectives: Radiomics has demonstrated potential in predicting the cytogenetic status of multiple myeloma (MM). However, the role of single-sequence radiomic nomograms in predicting the high-risk cytogenetic (HRC) status of MM remains underexplored. This study aims to develop and validate radiomic nomograms based on fat-suppressed T2-weighted images (T2WI-FS) for predicting MM's HRC status, facilitating pre-treatment decision-making and prognostic assessment. Materials and methods: A cohort of 159 MM patients was included, comprising 71 HRC and 88 non-HRC cases. Regions of interest within the most significant tumor lesions on T2WI-FS images were manually delineated, yielding 1688 features. Fourteen radiomic features were selected using 10-fold cross-validation, employing methods such as variance thresholds, Student's t-test, redundancy analysis, and least absolute shrinkage and selection operator (LASSO). Logistic regression was utilized to develop three prediction models: a clinical model (model 1), a T2WI-FS radiomic model (model 2), and a combined clinical-radiomic model (model 3). Receiver operating characteristic (ROC) curves evaluated and compared the diagnostic performance of these models. Kaplan-Meier survival analysis and log-rank tests assessed the prognostic value of the radiomic nomograms. Results: Models 2 and 3 demonstrated significantly greater diagnostic efficacy compared to model 1 (p < 0.05). The areas under the ROC curve for models 1, 2, and 3 were as follows: training set-0.650, 0.832, and 0.846; validation set-0.702, 0.730, and 0.757, respectively. Kaplan-Meier survival analysis indicated comparable prognostic values between the radiomic nomogram and MM cytogenetic status, with log-rank test results (p < 0.05) and concordance indices of 0.651 and 0.659, respectively; z-score test results were not statistically significant (p = 0.153). Additionally, Kaplan-Meier analysis revealed that patients in the non-HRC group, low-RS group, and aged ≤ 60 years exhibited the longest overall survival, while those in the HRC group, high-RS group, and aged > 60 years demonstrated the shortest overall survival (p = 0.004, Log-rank test). Conclusions: Radiomic nomograms are capable of predicting the HRC status in MM. The cytogenetic status, radiomics model Rad score, and age collectively influence the overall survival of MM patients. These factors potentially contribute to pre-treatment clinical decision-making and prognostic assessment.

A Cytogenetic Study of Turkish Children with Global Developmental Delay.

Global developmental delay (GDD)/intellectual disability (ID) is common in children and its etiology is unknown in many cases. Chromosomal abnormalities are predominant genetic causes of GDD/ID. The aim of this study is to determine the genetic risk factors that may be involved in the etiology of GDD/ID. In this study, 810 children with moderate to severe, clinically unexplained GDD/ID for whom cytogenetic analysis were performed were retrospectively rescreened. The results showed that GDD/ID affected more females than males (2 girls:1 boy). A total of 54 children (6.7%) with GDD showed chromosomal aberrations (CAs): 59.3% of these CAs were structural aberrations, and the rest were numerical aberrations (40.7%). Specifically, inversions, deletions, and reciprocal and robertsonian translocations, which were detected in 1, 0.7, 0.8, and 0.4% of the children, respectively, constituted important categories of structural CAs. Among numerical CAs, classic Turner and mosaics were detected in 1.2% of all children. Trisomy 21 and mosaic trisomy 21 were detected in 1% of the children. Marker chromosomes and 47,XXY karyotypes were found in two children each. Our results suggest that female sex is more affected by CAs among GDD/ID cases, and cytogenetic analysis is useful in the etiological diagnosis of GDD/ID.

Triaging and Evaluation of Products of Conception in Abortions and Post-Partum Hemorrhage.

The proper evaluation of abortion specimens and placentas from stillbirth and post-partum cases is important for adequate clinical care of post-abortion and post-partum patients. The following topics will be reviewed: (1) the importance of evaluation of both fetal and placental tissue in first trimester abortions to confirm an intrauterine pregnancy versus an ectopic pregnancy; (2) the clinical history associated with an abortion specimen or retained products of conception (POC) influences how the pathologist should triage the specimen; (3) the criteria for diagnosis of a molar pregnancy, which is critical for clinicians to know which patients need follow-up; (4) the utility of genetic studies for both diagnosis and appropriate follow-up of the patient; and (5) the pathologic evaluation of specimens from patients with post-partum hemorrhage for placenta accreta spectrum and subinvolution of maternal vessels.

Exploring the Effects of Robertsonian Translocation 1/29 (Rob (1;29)) on Genetic Diversity in Minor Breeds of Spanish Berrenda Cattle via Genome-Wide Analysis.

Most of the previous studies on the genetic variability in Spanish "Berrenda" breeds have been carried out using DNA microsatellites. The present work aimed to estimate the genetic diversity, population structure, and potential genetic differences among individuals of both Berrenda breeds and groups based on the presence of the Robertsonian chromosomal translocation, rob (1;29). A total of 373 samples from animals belonging to the two breeds, including 169 cases diagnosed as rob (1;29)-positive, were genotyped using an SNP50K chip. The genetic diversity at the breed level did not show significant differences, but it was significantly lower in those subpopulations containing the rob (1;29). Runs of homozygosity identified a region of homozygosity on chromosome 6, where the KIT (KIT proto-oncogene, receptor tyrosine kinase) gene, which determines the typical spotted coat pattern in both breeds, is located. The four subpopulations considered showed minor genetic differences. The regions of the genome that most determined the differences between the breeds were observed on chromosomes 4, 6, 18, and 22. The presence of this Robertsonian translocation did not result in sub-structuring within each of the breeds considered. To improve the reproductive performance of Berrenda breeds, it would be necessary to implement strategies considering the involvement of potential breeding stock carrying rob (1;29).

Blueberry Muffin Syndrome and Hyperleukocytosis in a Newborn: A Diagnostic Challenge.

Blueberry muffin syndrome (BMS) in neonates, characterized by widespread nodular lesions, presents diagnostic challenges due to its diverse etiologies. Hyperleukocytosis, with leukocyte counts exceeding 100,000/µL, is a rare phenomenon associated with severe complications in neonates. Congenital leukemia (CL), a rare diagnosis within the first month of life, is linked to high mortality. This case report presents a unique case of BMS with hyperleukocytosis as the initial presentation of CL. A full-term male newborn, born after an uncomplicated pregnancy, except for Kell isoimmunization, with an Apgar score of 9/10, and an irrelevant family history, showed widespread purple nodules consistent with BMS at birth. Laboratory workup revealed mild anemia, hyperleukocytosis with immature granulocytes on peripheral blood (PB) smear, positive direct antiglobulin test, and elevated alanine aminotransferase and lactate dehydrogenase, without hyperbilirubinemia. Empirical antibiotics and hyperhydration were started, and the neonate was transferred to a level 3 neonatal intensive care unit for further evaluation. A comprehensive etiological investigation was conducted, comprising infectious, immunological, metabolic, and neoplastic factors. A skin nodule biopsy revealed an infiltrate of blast cells, indicative of leukemia cutis, and a bone marrow aspirate confirmed acute myeloid leukemia (AML). The patient successfully completed the NOPHO-DBH-2012 chemotherapy protocol at five months and remains in complete remission at nine months. This case report contributes to the literature by highlighting the diagnostic approach and management strategies for CL presenting with BMS and hyperleukocytosis. This case aims to enhance awareness and understanding of BMS as an initial manifestation of CL. Additionally, the challenges of treating leukemia in neonates, coupled with the lack of specific guidelines for this age group, further underscore the complexities in managing such patients.

Outcomes with ibrutinib in patients with chronic lymphocytic leukaemia: Results from the German multicentre REALITY study.

OBJECTIVES: To assess treatment adherence, effectiveness and safety outcomes of patients with chronic lymphocytic leukaemia (CLL) receiving ibrutinib in a real-world setting. METHODS: Patients enrolled in REALITY were ≥18 years with a confirmed diagnosis of CLL and were receiving ibrutinib as a first-line (1L), 2L or ≥3L therapy. Treatment retention, adherence, progression-free survival (PFS), overall survival (OS) and time to next therapy were assessed at 1 and 2 years overall, by typology and by cytogenetic subgroups. PFS and OS were analysed using Kaplan-Meier methods. RESULTS: Exactly 302 patients were enrolled across 57 sites in Germany, from January 2017 to July 2021. One-year retention rates were 69.9% overall (primary endpoint), 77.9% for 1L patients, and 77.6%/78.8% for high-risk patients with del17p/TP53. At 2 years, PFS/OS rates were 77.8%/90.7% overall (1L, 82.7%/90.4%), and were consistent across cytogenetic subgroups. PFS rates were higher for 1L versus ≥3L patients. Patients with the low-acceptance/low-control typology at baseline were less likely to retain treatment at 1 year versus the high-acceptance/high-control typology. No new safety signals were observed. CONCLUSIONS: The REALITY study provides further evidence of the effectiveness and safety of ibrutinib in patients with CLL in a real-world setting, particularly in earlier treatment lines.

Isolated Increased Nuchal Translucency With Normal Chromosomal Study: A Case Report.

Increased nuchal translucency (NT) leads to a higher risk of fetal structural abnormalities. The measurement between 11 and 14 weeks gestation is a reliable marker for associated chromosomal abnormalities. Here, we present the case of a 33-year-old female with isolated high NT in the range of 5.6 mm at 12 weeks of gestational age. She was evaluated for chromosomal and structural abnormality and followed up meticulously. None of the tests showed any chromosomal or obvious structural abnormality. Fetal echocardiography revealed no structural cardiac defect. The pregnancy was uneventful and she delivered a healthy baby at term through lower (uterine)-segment cesarean section. The baby girl is living in good health without any developmental abnormalities. Although there is a high risk of chromosomal/structural defects with increased NT, it is not mandatory to terminate the pregnancy without a thorough evaluation.

From Genes to Ambiguity: A Case Study Exploring the Enigmatic Connection Between Chromosome 13q Deletion Syndrome and Ambiguous Genitalia.

During development, the deletion of DNA from chromosome 13's short arm (q) causes a chromosomal abnormality known as chromosome 13q deletion syndrome. Chromosome 13 terminal deletions are rare and may cause various congenital disabilities, and only a few cases have been reported in the literature. The extent of chromosome 13q deletion syndrome changes lacks consistent clinical features, with no recorded cases of genital ambiguity until now. We report the case of a newborn male patient whose testes had descended on both sides; he had ambiguous genitalia, and the dorsal surface of his penis was attached to his scrotal sac. An abnormal karyotype (46, XY, deletion (13) q33) was discovered by using a G-banding analysis of chromosomes in a blood sample taken from the periphery, which revealed a deletion of chromosome 13 at the end of the first 10 cells. We can better characterize chromosome 13q deletions by establishing stronger correlations between karyotype and the distinctive phenotypes of haploinsufficient genes found on the chromosome.

Clinical profile and cytogenetic correlations in females with primary amenorrhea.

OBJECTIVE: This study was conducted to investigate chromosomal abnormalities and their correlations with clinical and radiological findings in females with primary amenorrhea (PA). METHODS: Detailed forms were recorded for 470 females, including the construction of three-generation pedigrees. Peripheral venous blood was drawn, with informed consent, for cytogenetic analysis. RESULTS: An abnormal karyotype was found in 16.38% of participants. The incidence of structural abnormalities (6.8%) exceeded that of numerical abnormalities (6.15%). Turner syndrome represented 45% of all numerical abnormalities. Furthermore, the Y chromosome was detected in 5% of females with PA. Among the structural chromosomal abnormalities detected (n=32) were mosaicism (25%), deletions (12.5%), isochromosomes (18.75%), fragile sites (3.12%), derivatives (3.12%), marker chromosomes (3.12%), and normal variants (29.125%). An examination of secondary sexual characteristics revealed that 29.6% of females had a complete absence of breast development, 29.78% lacked pubic hair, and 36.88% exhibited no axillary hair development. Radiological findings revealed that 51.22% of females had a hypoplastic uterus and 26.66% had a completely absent uterus. Abnormal ovarian development, such as the complete absence of both ovaries, absence of one ovary, one absent and other streak, or both streak ovaries, was observed in 69.47% of females with PA. Additionally 43.1%, 36.1%, 67.4%, and 8% of females had elevated levels of serum follicle-stimulating hormone, luteinizing hormone, thyroid-stimulating hormone, and prolactin, respectively. CONCLUSION: This study underscores the importance of karyotyping as a fundamental diagnostic tool for assessing PA. The cytogenetic correlation with these profiles will aid in genetic counseling and further management of the condition.

Unravelling the Impact of an Additional Sex Chromosome in an Adult Female.

Women with Triple X syndrome (TXS) appear to be at increased risk for decreased ovarian reserve; however, available data are limited. We present an asyndromic adult female with features of recurrent pregnancy loss and decreased ovarian reserve detected with mosaic Triple X syndrome (TXS). The patient was initially evaluated by a low-cost peripheral blood (PB) conventional karyotyping using standard cytogenetic protocols. Interphase fluorescence in situ hybridisation was performed to confirm the diagnosis. Chromosomal microarray, which is a more expensive test, substantiated the presence of additional X chromosomes but failed to detect the presence of low level of mosaicism. Our case study emphasised the recommendation of performing a strategy-based cost-effective cytogenetic evaluation of all cases of decreased ovarian reserve or low anti-Müllerian hormone levels in a resource-constrained setting. It also highlighted the need for additional research to understand the natural history of ovarian function in TXS affected women throughout their lifespans.

BCR::ABL1-like acute lymphoblastic leukaemia: a single institution experience on identification of potentially therapeutic targetable cases.

BACKGROUND: BCR::ABL1-like acute lymphoblastic leukaemia (BCR::ABL1-like ALL) is characterized by inferior outcomes. Current efforts concentrate on the identification of molecular targets to improve the therapy results. The accessibility to next generation sequencing, a recommended diagnostic method, is limited. We present our experience in the BCR::ABL1-like ALL diagnostics, using a simplified algorithm. RESULTS: Out of 102 B-ALL adult patients admitted to our Department in the years 2008-2022, 71 patients with available genetic material were included. The diagnostic algorithm comprised flow cytometry, fluorescent in-situ hybridization, karyotype analysis and molecular testing with high resolution melt analysis and Sanger Sequencing. We recognized recurring cytogenetic abnormalities in 32 patients. The remaining 39 patients were screened for BCR::ABL1-like features. Among them, we identified 6 patients with BCR::ABL1-like features (15.4%). Notably, we documented CRLF2-rearranged (CRLF2-r) BCR::ABL1-like ALL occurrence in a patient with long-term remission of previously CRLF2-r negative ALL. CONCLUSIONS: An algorithm implementing widely available techniques enables the identification of BCR::ABL1-like ALL cases in settings with limited resources.

Hallazgos citogenéticos y edad materna en pacientes con síndrome down en un hospital de referencia pediátrico en el Perú

Introducción: El síndrome Down es un trastorno congénito originado por una trisomía total o parcial del cromosoma 21 y es considerada la causa genética más común de malformaciones congénitas y discapacidad intelectual. El objetivo de este estudio fue describir las alteraciones citogenéticas de pacientes con Síndrome Down y su relación con la edad materna. Métodos: Estudio transversal, descriptivo-analítico. Se incluyó 436 pacientes con Síndrome Down admitidos en el Instituto Nacional de Salud del Niño durante el período 2017-2019. Se analizaron las variables: alteración citogenética y edad materna. Resultados: Se encontró que el 99,3% (n=433) de pacientes presentaron algún tipo de alteración citogenética y tres pacientes presentaron cariotipo normal. La edad de los pacientes al momento de la toma de muestra estuvo comprendida entre los 0,03 y 17 años, la relación masculino/femenino fue de 1.2:1. La alteración citogenética más frecuente fue la trisomía 21 libre (94,7%), seguida por la translocación Robertsoniana (n=16) y el mosaicismo (n=6). En el caso de la edad materna se encontró una mediana de 37 años (rango: 13-47). Conclusiones: La trisomía 21 libre es la alteración citogenética más común en Síndrome Down; sin embargo, la translocación Robertsoniana y los mosaicismos fueron más frecuentes en edad materna menor de 35 años, sugiriendo que existe otros factores de riesgo diferentes a la edad materna avanzada en este grupo etario.

Introduction: Down syndrome is a congenital disorder caused by a total or partial trisomy of chromosome 21 and is considered the most common genetic cause of congenital malformations and intellectual disability. The objective of this study was to describe the cytogenetic alterations of patients with Down syndrome and their relationship with maternal age. Methods: Cross-sectional, descriptive-analytical study. 436 patients with Down syndrome admitted to the Instituto Nacional de Salud del Niño during the 2017-2019 period were included. The variables analyzed were: cytogenetic diagnosis and maternal age. Results: It was found that 99,3% (n=433) of patients presented some type of cytogenetic alteration and three patients presented a normal karyotype. The age of the patients at the time of sampling was between 0,03 and 17 years, the male/female ratio was 1.2:1. The most frequent cytogenetic alteration was free trisomy 21 (94,7%), followed by Robertsonian translocation (n=16) and mosaicism (n=6). In the case of maternal age, a median of 37 years was found (range: 13-47). Conclusions: Free trisomy 21 is the most common cytogenetic condition in Down syndrome; however, the Robertsonian translocation and mosaicisms were more frequent in patients whose mothers were les than 35 years old, suggesting that there are other risk factors than advanced maternal age in this group.

Molecular genetic analysis of 1,980 cases of male infertility.

The present study aimed to investigate the occurrence of chromosomal karyotype abnormalities and azoospermia factor (AZF) microdeletion on the long arm of the Y chromosome (Yq) in infertile men, and to determine their association with infertility to ultimately improve clinical outcomes in these patients. A total of 1,980 azoospermic and oligospermic men from the outpatient department of the Fujian Maternity and Child Health Hospital (Fuzhou, China) were recruited between January 2016 and December 2019. Peripheral blood was used for karyotype analysis; AZF microdeletion analysis of the Yq was performed using capillary electrophoresis. Among the 1,980 patients, 178 had chromosomal abnormalities (9.0%; 178/1,980), of whom 98 had an abnormal number of chromosomes. Among the abnormal karyotypes, the most common was 47, XXY (80/178; 44.9%). AZF microdeletion on the Yq occurred at a rate of 10.66% (211/1,980); the most common type was the AZFb/c deletion (sY1192; 140/211; 66.4%). The present findings showed that karyotype abnormalities and AZF gene microdeletion are important drivers of male infertility. Specifically, men with Yqh- and del(Y)(q11) had a higher risk of AZF microdeletion. These results suggested that patient treatment could be personalized based on routine molecular genetic analysis, which could further alleviate the economic and emotional burden of undergoing redundant or ineffective treatments.

Individual Risk Assessment for Population Living on the Territories Long-Term Polluted by Organochlorine Pesticides.

The long-term storage of unutilized pesticides raised new problems of long-term environmental contamination. The study presents the results of surveying 151 individuals in 7 villages living close to pesticide-contaminated localities. All individuals have been surveyed concerning their consumption habits and lifestyle characteristics. An assessment of the general exposure risks of the local population was carried out using the analysis of pollutants in food products and the average levels of their consumption in the region. The cohort risk evaluation revealed that the greatest risk was associated with the regular consumption of cucumbers, pears, bell peppers, meat, and milk. The new model to estimate individual risks of long-term pesticide pollution was proposed as a calculation of the combined action of 9 risk factors, including individual genotypes, age, lifestyle, and personal pesticide consumption rates. The analysis of the predictive ability of this model showed that the final score for individual health risks corresponded to the development of chronic diseases. A high level of chromosomal aberrations was evidenced for individual genetic risk manifestations. The combined influence of all risk factors revealed contributions of 24.7% for health status and 14.2% for genetic status, while other impacts go to all unaccounted factors.

Shallow whole-genome sequencing of bone marrow aspirates in myelodysplastic neoplasms: A retrospective comparison with cytogenetics.

Copy number alterations (CNA) are powerful prognostic markers in myelodysplastic neoplasms (MDS) and are routinely analyzed by conventional cytogenetic analysis (CCA) on bone marrow (BM). Although CCA is still the gold standard, it requires extensive hands-on time and highly trained staff for the analysis, making it a laborious technique. To reduce turn-around-time per case, shallow whole genome sequencing (sWGS) technologies offer new perspectives for the diagnostic work-up of this disorder. We compared sWGS with CCA for the detection of CNAs in 33 retrospective BM samples of patients with MDS. Using sWGS, CNAs were detected in all cases and additionally allowed the analysis of three cases for which CCA failed. The prognostic stratification (IPSS-R score) of 27 out of 30 patients was the same with both techniques. In the remaining cases, discrepancies were caused by the presence of balanced translocations escaping sWGS detection in two cases, a subclonal aberration reported with CCA that could not be confirmed by FISH or sWGS, and the presence of an isodicentric chromosome idic(17)(p11) missed by CCA. Since sWGS can almost entirely be automated, our findings indicate that sWGS is valuable in a routine setting validating it as a cost-efficient tool.

A New Case of Translocation T(2;7)(p23;q35) in Recurrent Pregnancy Loss.

Recurrent pregnancy loss is a phenomenon caused by many etiologies. The majority of these causes are chromosomal anomalies. In this case report, cytogenetic analysis was performed on the family who consulted our department with the complaint of recurrent pregnancy loss. A normal karyotype was found in the female (46, XX); however, t(2;7)(p23;q35) translocation was detected in the male. Reciprocal translocations are a common class of chromosomal abnormalities, and we anticipate this case of translocation will be a new cause for recurrent pregnancy loss. In the analysis, preparations at the level of 500 bands were examined, and at least 20 metaphase areas were evaluated. From the results of cytogenetic and FISH (fluorescence in situ hybridization) analysis, we determined the male had t(2;7)(p23;q35) chromosomal anomaly. The probe binding the patient's 2p23 region signaled at the q-terminal of chromosome 7; however, the other two chromosomes (2 and 7) were normal. There is no report of such a case in the literature for recurrent pregnancy loss complaints. With this case, it will be reported for the first time that an embryo formed with the gametes carrying unbalanced genetic material of an individual with the karyotype 46, XY, t(2;7)(p23;q35) is incompatible with life.

Clinical and Molecular Characteristics of Patients with Mixed Phenotype Acute Leukemia.

INTRODUCTION: Mixed phenotype acute leukemia (MPAL) is a rare heterogeneous disease with a poor prognosis. This study analyzed the clinical, immunophenotypic, molecular, and cytogenetic characteristics of a group of patients with MPAL. METHODS: This prospective study included 75 patients diagnosed with MPAL according to the World Health Organization (WHO)-2016 diagnostic criteria, using cytochemistry, conventional cytogenetics, and molecular studies. Screening of BCR::ABL1 fusion gene was performed by Fluorescent in-situ hybridization (FISH) and polymerase chain reaction (PCR). RESULTS: Children represented 49.3% of MPAL patients. The main phenotype was B-lymphoid/myeloid (80%). Molecular alterations were detected in 17 patients (22.7%). The BCR::ABL1 fusion gene was detected in 10 patients (13.3%).. Myeloid protocols were used to treat 58 patients (77.3%), and lymphatic protocols in 17. By the end of the follow-up, 57 patients (76%) achieved complete remission (CR). There was no association between BCR::ABL1 and response to treatment. The cumulative overall survival (OS) at 12 months was 47.8%. The bone marrow transplantation (BMT) was associated with better OS (p = 0.027). The disease-free survival (DFS) was not affected by all tested prognostic factors. CONCLUSION: MPAL is a complex entity with heterogeneous features. BCR::ABL1 is a common abnormality. BMT is associated with better OS.

Physical mapping of a new powdery mildew resistance locus from Thinopyrum ponticum chromosome 4AgS.

Thinopyrum ponticum (Podp.) Barkworth and D.R. Dewey is a decaploid species that has served as an important genetic resource for improving wheat for the better part of a century. The wheat-Th. ponticum 4Ag (4D) disomic substitution line Blue 58, which was obtained following the distant hybridization between Th. ponticum and common wheat, has been stably resistant to powdery mildew under field conditions for more than 40 years. The transfer of 4Ag into the susceptible wheat cultivar Xiaoyan 81 resulted in powdery mildew resistance, indicating the alien chromosome includes the resistance locus. Irradiated Blue 58 pollen were used for the pollination of the recurrent parent Xiaoyan 81, which led to the development of four stable wheat-Th. ponticum 4Ag translocation lines with diverse alien chromosomal segments. The assessment of powdery mildew resistance showed that translocation line L1 was susceptible, but the other three translocation lines (WTT139, WTT146, and WTT323) were highly resistant. The alignment of 81 specific-locus amplified fragments to the Th. elongatum genome revealed that 4Ag originated from a group 4 chromosome. The corresponding physical positions of every 4Ag-derived fragment were determined according to a cytogenetic analysis, the amplification of specific markers, and a sequence alignment. Considering the results of the evaluation of disease resistance, the Pm locus was mapped to the 3.79-97.12 Mb region of the short arm of chromosome 4Ag. Because of its durability, this newly identified Pm locus from a group 4 chromosome of Th. ponticum may be important for breeding wheat varieties with broad-spectrum disease resistance.

Mutational profile, outcomes, and impact of allogeneic hematopoietic stem cell transplantation in adult patients with acute myeloid leukemia and inconclusive cytogenetic analysis.

BACKGROUND: Inconclusive cytogenetic analysis (IC) at baseline has been reported as a predictor of poor prognosis in patients with acute myeloid leukemia (AML). The mutational profile in this group of patients, and its impact on outcomes have not been reported. METHODS: We retrospectively analyzed adult patients (≥18 years) with newly diagnosed AML treated with intensive induction chemotherapy between 2015 and 2019. Patients with any documented cytogenetic abnormalities were excluded. Targeted next generation sequencing (NGS) was performed in all patients. Baseline characteristics, mutation profile, and outcomes were compared between patients with normal cytogenetics(NC) and those with IC. RESULTS: Sixty-one patients (males 39.3%; median age 59 years) had IC at diagnosis. The proportion of patients with mutations in genes with proven prognostic impact were not different between AML patients with IC and NC. AML patients with NC were more likely to harbor the prognostically favorable NPM1mut /FLT3-ITDwt mutational combination conferring "favorable" risk status. As a result, a larger proportion of patients in the IC group underwent allogeneic hematopoietic stem cell transplantation (allo HCT; 54.1% vs. 39.6%; p = .02). The 2-year RFS (55.9% vs. 58.5%; p = .29) and OS (61.9% vs. 66.9%; p = .48) were similar in IC and NC patients. There was no difference in survival of patients who underwent allo HCT when compared with patients who did not (p = .99). CONCLUSIONS: Inconclusive cytogenetic analysis may not be an independent prognostic indicator in AML. In such patients, molecular abnormalities detected through NGS or whole genome sequencing are more likely to be informative.