The Use of Genomic Screening for the Detection of Chromosomal Abnormalities in the Domestic Horse: Five New Cases of 65,XXY Syndrome in the Pura Raza Español Breed.

Sex chromosomal abnormalities are a well-established cause of reproductive failure in domestic horses. Because of its difficult diagnosis, the Pura Raza Español breeding program established a routine screening for chromosomal abnormalities in all the horses prior to enrolling in the studbook. This genomic procedure combines an initial assessment based on the results from Short Tandem Repeat (STR) parentage testing followed by a Single-Nucleotide Polymorphism (SNP) based copy number aberration (CNA) confirmative analysis in positive cases. Using this methodology, we identified five new individuals carrying a 65,XXY chromosomal number aberration (CNA) among 27,330 foals enrolled over the past two reproductive seasons. The animals were initially flagged as CNA candidates due to abnormal results in STR testing. Subsequent analysis genotyping using an STR sex-linked dedicated panel and a medium-density SNP array in ECAX and ECAY confirmed the diagnosis as 65,XXY carriers. Four cases (upon sample availability) underwent further analysis using in situ fluorescent hybridization with ECAX and ECAY probes, showing identical results. Phenotypic analysis revealed abnormal gonad development in one of the cases, showing that the remaining four had a normal reproductive morphology. To our knowledge, this represents the largest number of horses exhibiting the equine form of Klinefelter syndrome (65,XXY) reported to date. Our study highlights the importance of genomic screening in the accurate detection of chromosomal abnormalities in horses.

Flow cytometric expression of Bcl-2, Mcl-1, and their ratios correlates with primary and secondary cytogenetic changes and their combinations in multiple myeloma.

Response to BH3 mimetics in multiple myeloma (MM) correlates with CCND1-rearrangement or expression of anti-apoptotic molecules, particularly Bcl-2 and Mcl-1. Our study investigates the relationship between cytogenetic abnormalities (CGAs) and intracellular Bcl-2 and Mcl-1 expression in myeloma plasma cells (MPCs) using flow cytometry (FCM). We measured median fluorescence intensity (MFI) of Bcl-2 and Mcl-1 in 163 bone marrow samples (143 MM, 20 controls) across various cell types. Both Bcl-2MFI and Mcl-1MFI were significantly higher in MPCs compared to other cells, with Bcl-2 MFI exceeding Mcl-1 MFI in MPCs. Bcl-2 expression peaked in CCND1-rearranged cases, while Mcl-1 expression was highest in cases with 1q21 gain/amplification. Notably, 65-74% of cases with other CGAs exhibited moderate to strong Bcl-2 or Mcl-1 expression, indicating potential utility of BH3 mimetics in this group, while 25% showed dim to absent expression of one or both markers, suggesting potential futility in these patients. Our study highlights FCM's potential for rapid Bcl-2 and Mcl-1 quantification, surpassing traditional methods. We propose that direct measurement of Bcl-2 and Mcl-1 expression in PCs by FCM, combined with cytogenetic characterization, could improve therapeutic decision-making regarding the use of BH3 mimetics in MM, potentially enhancing outcomes and overcoming resistance.

Satellitome analysis on the pale-breasted thrush Turdus leucomelas (Passeriformes; Turdidae) uncovers the putative co-evolution of sex chromosomes and satellite DNAs.

Do all birds' sex chromosomes follow the same canonical one-way direction of evolution? We combined cytogenetic and genomic approaches to analyze the process of the W chromosomal differentiation in two selected Passeriform species, named the Pale-breasted Thrush Turdus leucomelas and the Rufous-bellied thrush T. rufiventris. We characterized the full catalog of satellite DNAs (satellitome) of T. leucomelas, and the 10 TleSatDNA classes obtained together with 16 microsatellite motifs were in situ mapped in both species. Additionally, using Comparative Genomic Hybridization (CGH) assays, we investigated their intragenomic variations. The W chromosomes of both species did not accumulate higher amounts of both heterochromatin and repetitive sequences. However, while T. leucomelas showed a heterochromatin-poor W chromosome with a very complex evolutionary history, T. rufiventris showed a small and partially heterochromatic W chromosome that represents a differentiated version of its original autosomal complement (Z chromosome). The combined approach of CGH and sequential satDNA mapping suggest the occurrence of a former W-autosomal translocation event in T. leucomelas, which had an impact on the W chromosome in terms of sequence gains and losses. At the same time, an autosome, which is present in both males and females in a polymorphic state, lost sequences and integrated previously W-specific ones. This putative W-autosomal translocation, however, did not result in the emergence of a multiple-sex chromosome system. Instead, the generation of a neo-W chromosome suggests an unexpected evolutionary trajectory that deviates from the standard canonical model of sex chromosome evolution.

Translocation (11;14) is a common cytogenetic abnormality in clonal plasma cells in monoclonal immunoglobulin deposition disease.

Monoclonal Immunoglobulin deposition disease (MIDD) is characterised by deposits of intact monoclonal light chains in the kidney leading to renal dysfunction. In this study, we retrospectively investigated the underlying plasma cell cytogenetic abnormalities in MIDD. CyclinD1 (11;14) translocation was identified in 12/27 (45%) patients. Among the patients without translocation, del13q and hyperdiploidy were the most common abnormalities. Patients in the non-t (11;14) group had a higher baseline light-chain ratio, higher proteinuria and lower eGFR as compared to patients with t (11;14). Haematological VGPR or higher was seen in 58% of t (11;14), and 30% without t (11;14), possibly related to higher use of Daratumumab-based therapy in the t (11;14) group. With a median follow-up of 750 days, 30% (8/24) progressed to end stage renal disease (ESRD). eGFR <20 mL/min (HR 25, 95% CI 2.09-298, p = 0.01) and 24 urine protein >3 g/24 h (HR 9, 95% CI 1.27-63.90, p = 0.02) at diagnosis were significantly associated with progression to ESRD. Renal survival was better in t (11;14) as compared to the non-t (11;14) group (HR 0.11, p = 0.06). Translocation (11;14) is a common abnormality in MIDD and affects the presentation and outcomes. Identification of this abnormality should lead to exploration of BCL2 inhibitors in this disease.

BR-ChromNet: Banding resolution localization of chromosome structural abnormality with conditional random field.

Detecting chromosome structural abnormalities in medical genetics is essential for diagnosing genetic disorders and understanding their implications for an individual's health. However, existing computational methods are formulated as a binary-class classification problem trained only on representations of positive/negative chromosome pairs. This paper introduces an innovative framework for detecting chromosome abnormalities with banding resolution, capable of precisely identifying and masking the specific abnormal regions. We highlight a pixel-level abnormal mapping strategy guided by banding features. This approach integrates data from both the original image and banding characteristics, enhancing the interpretability of prediction results for cytogeneticists. Furthermore, we have implemented an ensemble approach that pairs a discriminator with a conditional random field heatmap generator. This combination significantly reduces the false positive rate in abnormality screening. We benchmarked our proposed framework with state-of-the-art (SOTA) methods in abnormal screening and structural abnormal region segmentation. Our results show cutting-edge effectiveness and greatly reduce the high false positive rate. It also shows superior performance in sensitivity and segmentation accuracy. Being able to identify abnormal regions consistently shows that our model has demonstrated significant clinical utility with high model interpretability. BRChromNet is open-sourced and available at https://github.com/frankchen121212/BR-ChromNet.

Cancer cytogenetics in the era of artificial intelligence: shaping the future of chromosome analysis.

Artificial intelligence (AI) has rapidly advanced in the past years, particularly in medicine for improved diagnostics. In clinical cytogenetics, AI is becoming crucial for analyzing chromosomal abnormalities and improving precision. However, existing software lack learning capabilities from experienced users. AI integration extends to genomic data analysis, personalized medicine and research, but ethical concerns arise. In this article, we discuss the challenges of the full automation in cytogenetic test interpretation and focus on its importance and benefits.

Cytogenetics and genomics in CML and other myeloproliferative neoplasms.

Chronic myeloid leukemia is defined by the presence of the Philadelphia translocation t (9; 22) resulting in the BCR::ABL1 fusion. The other myeloproliferative neoplasms (MPN) subtypes also carry typical chromosomal abnormalities, which however are not pathognomonic for a specific entity of MPN. According to the WHO classification the distinction between these entities is still based on the integration of cytological, histopathological and molecular findings. Progression of CML into accelerated and blastic phase is usually driven by additional chromosome abnormalities and ABL1 kinase mutations. In the other MPN subtypes the additional mutations besides driver gene mutations in JAK2, MPL and CALR have a decisive impact on the propensity for progression. In addition, the sequence in which the driver mutations and risk conveying additional mutations have been acquired appears to play an important role. Here, we review cytogenetic and molecular changes in CML and MPN that should be evaluated during diagnosis and disease monitoring.

The challenges and opportunities of offering and integrating training in clinical molecular genetics and clinical cytogenetics: A survey of LGG Fellowship Program Directors.

Purpose: The specialty of Laboratory Genetics and Genomics (LGG) was created in 2017 in an effort to reflect the increasing convergence in technologies and approaches between clinical molecular genetics and clinical cytogenetics. However, there has not yet been any formal evaluation of the merging of these disciplines and the challenges faced by Program Directors (PDs) tasked with ensuring the successful training of laboratory geneticists under the new model. Methods: An electronic multi-question Qualtrics survey was created and was sent to the PD for each of the Accreditation Council for Graduate Medical Education-accredited LGG fellowship programs at the time. The data were collected, and the responses were aggregated for each question. Results: All of the responding PDs had started training at least 1 LGG fellow. PDs noted challenges with funding, staff shortages, molecular/cytogenetics content integration, limited total training time, increased remote work, increased sendout testing, and a lack of prior cytogenetics knowledge among incoming fellows. Conclusion: This survey attempted to assess the challenges that LGG PDs have been facing in offering and integrating clinical molecular genetics and clinical cytogenetics fellowship training. Common challenges between programs were noted, and a set of 6 concluding comments are provided to facilitate future discussion.

Genomic structural variants analysis in leukemia by a novel cytogenetic technique: Optical genome mapping.

Genomic structural variants (SVs) play a pivotal role in driving the evolution of hematologic malignancies, particularly in leukemia, in which genetic abnormalities are crucial features. Detecting SVs is essential for achieving precise diagnosis and prognosis in these cases. Karyotyping, often complemented by fluorescence in situ hybridization and/or chromosomal microarray analysis, provides standard diagnostic outcomes for various types of SVs in front-line testing for leukemia. Recently, optical genome mapping (OGM) has emerged as a promising technique due to its ability to detect all SVs identified by other cytogenetic methods within one single assay. Furthermore, OGM has revealed additional clinically significant SVs in various clinical laboratories, underscoring its considerable potential for enhancing front-line testing in cases of leukemia. This review aims to elucidate the principles of conventional cytogenetic techniques and OGM, with a focus on the technical performance of OGM and its applications in diagnosing and prognosticating myelodysplastic syndromes, acute myeloid leukemia, acute lymphoblastic leukemia, and chronic lymphocytic leukemia.

Breaking the association between gametocidal gene(s) and leaf rust resistance gene (LrS2427) in Triticum aestivum-Aegilops speltoides derivative by gamma irradiation.

Utilization of crop wild relatives of wheat can be very effective in building the genetic diversity to cater to the evolving strains of disease pathogens. Aegilops speltoides is a rich source of rust resistance genes however transferring those to wheat genome can be tedious due to co-transfer and preferential transmission of undesirable genes causing gametocidal activity. Such an unholy association was observed in Triticum aestivum-Ae. speltoides derivative line Sel. 2427 which possess the broad-spectrum leaf rust seedling resistance gene (LrS2427). Molecular analysis based on 35 K wheat breeder's array revealed the maximum percentage of Ae. speltoides genome introgression on homoeologous group 2. In situ hybridization studies revealed the presence of S genome in Sel. 2427, showing six translocations on four chromosomes. Karyotyping using repetitive probe (AAG)6 revealed that the two chromosomes involved are 2D and 2B. Genic regions causing gametocidal activity were identified by dissecting it into component traits and QTLs on 2D and 2B chromosomes were revealed in case of the trait seed shrivelling index. To break the inadvertent association of LrS2427 with gametocidal genes, F1(Agra Local X Sel. 2427) seeds were irradiated with gamma rays and stable leaf rust resistant mutants lacking gametocidal activity were developed. These mutants showed resistance to different races of leaf rust pathogen and showed superior agronomic performance as well. These mutants could be a great resource in wheat improvement for utilization of the leaf rust resistance gene LrS2427 without any yield penalty. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01491-8.

Automated Quantification of Meiotic Recombination Foci Position and Intensity.

During meiosis, homologous chromosomes reciprocally exchange segments of DNA via the formation of crossovers. However, the frequency and position of crossover events along chromosomes are not random. Each chromosome must receive at least one crossover, and the formation of a crossover at one location inhibits the formation of additional crossovers nearby. These crossover patterning phenomena are referred to as "crossover assurance" and "crossover interference," respectively. One key method for quantifying meiotic crossover patterning is to immunocytologically measure the position and intensity of crossover-associated protein foci along the length of meiotic prophase I chromosomes. This approach was recently used to map the position of a conserved E3 ligase, HEI10, along Arabidopsis pachytene chromosomes, providing experimental support for a novel mechanistic "coarsening model" for crossover patterning. Here we describe a user-friendly method for automatically measuring the position and intensity of recombination-associated foci along meiotic prophase I chromosomes that is broadly applicable to studies in different eukaryotic species.

Immunophenotypic, genetic, and clinical characterization of adult T-cell leukemia/lymphoma: A single tertiary care center experience in the United States.

OBJECTIVES: Adult T-cell leukemia/lymphoma (ATLL) is an aggressive mature T-cell neoplasm caused by human T-cell lymphotropic virus type 1 (HTLV-1). Its most common immunophenotype is CD4+/CD7-/CD25+, although unusual immunophenotypes can occur and may lead to misdiagnosis. METHODS: The immunophenotypes, cytogenetics, molecular features, clinical presentations, treatment, and prognosis of 131 patients with ATLL were retrospectively studied in a large tertiary medical center in the United States. RESULTS: All cases showed loss of CD7 expression. While 82.4% of cases demonstrated CD4+, 17.6% exhibited unusual phenotypes, including CD4+/CD8+ (6.9%), CD4-/CD8- (2.3%), CD5- (3.1%), CD2-, and CD3-. The most common cytogenetics abnormalities included polysomy 3 (34.6%), translocation 1 (23.1%), and abnormalities found on chromosome 11 (30.8%) and chromosome 14 (26.9%). The common gene mutations identified by the next-generation sequencing study were TP53 (16.7%), TBL1XR1 (16.7%), EP300 (14.3%), and NOTCH1 (14.3%). TBL1XR1 mutation is associated with genetic instabilities. There was no significant difference between the clinical presentations of these 2 groups. CONCLUSIONS: Adult T-cell leukemia/lymphoma exhibits versatile immunophenotypic, cytogenetic, and molecular features. Simultaneous involvement of blood, lymph nodes, and other organs, along with hypercalcemia in a patient from an endemic area, necessitates HTLV-1 testing to avoid underdiagnosis of this dismal disease that might need aggressive chemotherapy followed by bone marrow transplant.

[Cytoplasmic light-chain immunofluorescence combined with FISH in bone marrow smears to detect cytogenetic abnormalities in multiple myeloma].

Objective: To analyze the sensitivity of cytoplasmic light-chain immunofluorescence with fluorescence in situ hybridization in bone marrow smears (new FISH) for detecting cytogenetic abnormalities in multiple myeloma (MM) . Methods: 42 MM patients admitted to the First Affiliated Hospital of Nanjing Medical University from April 2022 to October 2023 were enrolled. The patients with MM were detected by new FISH and CD138 immunomagnetic bead sorting technology combined with FISH (MACS-FISH) or cytoplasmic immunoglobulin FISH (cIg-FISH) to analyze cytogenetic detection results using combination probes which included 1q21/1p32, p53, IgH, IgH/FGFR3 [t (4;14) ], and IgH/MAF [t (14;16) ]. Results: In 23 patients with MM, the abnormality detection rates of cIg-FISH and new FISH were 95.7% and 100.0%, respectively (P>0.05). The detection rates of 1q21+, 1p32-, p53 deletion, and IgH abnormalities by cIg-FISH and new FISH were consistent, which were 52.2%, 8.7%, 17.4%, and 65.2%, respectively. The results of the two methods further performed with t (4;14) and t (14;16) in patients with IgH abnormalities were identical. The positive rate of t (4;14) was 26.7%, whereas t (14;16) was not detected. In 19 patients with MM, the abnormality detection rates of MACS-FISH and new FISH were 73.7% and 63.2%, respectively (P>0.05). The positivity rate of 1q21+, 1p32- and IgH abnormalities detected by MACS-FISH were slightly higher than those detected by new FISH; however, the differences were not statistically significant (all P values >0.05) . Conclusion: The new FISH method has a higher detection rate of cytogenetic abnormalities in patients with MM and has good consistency with MACS-FISH and cIg-FISH.

Venetoclax-based non-intensive induction followed by allogenic stem-cell transplantation in elderly acute myeloid leukemia patients with adverse cytogenetics.

INTRODUCTION: Elderly acute myeloid leukemia (AML) patients with poor-risk cytogenetics have a poor outcome with intensive chemotherapy (IC). While Venetoclax (VEN) has changed the outcomes of elderly unfit patients treatment, it is unknown whether it could be effective in poor-risk cytogenetics 60-75 years old patients. MATERIALS AND METHODS: We included 60-75-year-old AML patients eligible to allogenic stem cell transplantation (allo-SCT) treated with VEN (combined with azacitidine or with Cladribin and Aracytine) at Institut Paoli Calmettes, between 2020 and 2023 and compared this cohort with patients treated by IC between 2010 and 2019. RESULTS: Twenty six patients were treated with VEN (17 in combination with azacitidine and 9 with Cladribin and Aracytine) and 90 were treated with IC. Thirteen patients (50%) had a TP53 mutation. The median time for leucocyte and platelet counts recovery was 26 days (range 0-103) and 26 days (range, 0-63). The median duration of the first hospitalization was 32 days (ranges, 7-79). The composite response rate was 69% (CR = 50%, CRi = 4%, MLFS = 15%). Allo-SCT could be performed in 42% of cases. Median overall survival (OS) was 7.9 months (20.9 months in the group of patients who transitioned to allo-SCT). We found no difference with the historical cohort of patients treated with IC except a trend toward less lower and upper tract gastro-intestinal (GI) tract infections in the VEN group (respectively 8% vs 26%, p = .06; and 0% vs. 13% p = .06). CONCLUSION: VEN-based treatment was found to be effective in high risk AML can be considered as an alternative to IC in patients aged 60-75 with adverse cytogenetics.

Improving genetic testing utilization in a tertiary care neonatal intensive care unit through quality improvement.

There is an increasing recognition of the importance of diagnosing genetic conditions with an ever-growing list of genetic testing options. However, most providers do not have formal genetics training, which makes choosing the most appropriate test to order challenging. Our project sought to improve cytogenetic testing utilization in a tertiary care neonatal intensive care unit (NICU) through utilizing quality improvement techniques, specifically the Model for Improvement framework with rapid Plan-Do-Study-Act cycles. Our project utilized various interventions including the implementation of a NICU genetic testing algorithm. Interventions demonstrated improvement in all areas, specifically a 92% reduction in unnecessary cytogenetic testing with improvement in the diagnostic rate. Our work also resulted in a 59% decrease in charges with an estimated projected savings of $21,000 per year. Quality improvement can minimize redundancies and inefficiencies in genetic testing in a Level IV NICU in a large tertiary care children's hospital and result in substantial cost-savings.

Whole Exome Sequencing of Intermediate-Risk Acute Myeloid Leukemia without Recurrent Genetic Abnormalities Offers Deeper Insights into New Diagnostic Classifications.

Two new diagnostic classifications of acute myeloid leukemia (AML) were published in 2022 to update current knowledge on disease biology. In previous 2017-edition categories of AML with myelodysplasia-related changes, AML was not otherwise specified, but AML with mutated RUNX1 experienced profound changes. We performed whole exome sequencing on a cohort of 69 patients with cytogenetic intermediate-risk AML that belonged to these diagnostic categories to correlate their mutational pattern and copy-number alterations with their new diagnostic distribution. Our results show that 45% of patients changed their diagnostic category, being AML myelodysplasia-related the most enlarged, mainly due to a high frequency of myelodysplasia-related mutations (58% of patients). These showed a good correlation with multilineage dysplasia and/or myelodysplastic syndrome history, but at the same time, 21% of de novo patients without dysplasia also presented them. RUNX1 was the most frequently mutated gene, with a high co-occurrence rate with other myelodysplasia-related mutations. We found a high prevalence of copy-neutral loss of heterozygosity, frequently inducing a homozygous state in particular mutated genes. Mild differences in current classifications explain the diagnostic disparity in 10% of patients, claiming a forthcoming unified classification.

Non-Secretory Multiple Myeloma Associated With High-Risk Phenotype and Complex Cytogenetics Including t(8;22).

Multiple myeloma (MM) is a plasma cell dyscrasia which is typically characterized by identifiable paraprotein in the blood or urine. However, the minority of patients in whom paraprotein cannot be identified are designated non-secretory MM (NSM). Evaluation of treatment response is more difficult in these patients as paraprotein levels cannot be followed. A dearth of clinical trials including these patients exists because of an inability to measure response by classical serum and urine measurement mechanisms as well as seemingly decreased overall survival compared to secretory MM. NSM is subdivided into four subgroups: "non-producers", "true non-secretors", "oligosecretors" and "false non-secretors". The "non-producers" phenotype is associated with more aggressive disease course. Translocations such as those involving the proto-oncogene c-MYC (chromosome 8) and the lambda light chain gene IGL (chromosome 22) - more commonly associated with Burkitt lymphoma - are rare in MM. We describe a 60-year-old male with NSM who was identified as having multiple high-risk features including complex cytogenetics and a non-producer phenotype, which are features not considered in conventional MM staging and risk stratification. This case highlights the need for awareness of phenotypes and cytogenetics associated with higher clinical risk that are not included in the revised International Staging System.

Use of peptide nucleic acid probe to determine telomere dynamics in improving chromosome analysis in genetic toxicology studies.

Genetic toxicology, strategically located at the intersection of genetics and toxicology, aims to demystify the complex interplay between exogenous agents and our genetic blueprint. Telomeres, the protective termini of chromosomes, play instrumental roles in cellular longevity and genetic stability. Traditionally karyotyping and fluorescence in situ hybridisation (FISH), have been indispensable tools for chromosomal analysis following exposure to genotoxic agents. However, their scope in discerning nuanced molecular dynamics is limited. Peptide Nucleic Acids (PNAs) are synthetic entities that embody characteristics of both proteins and nucleic acids and have emerged as potential game-changers. This perspective report comprehensively examines the vast potential of PNAs in genetic toxicology, with a specific emphasis on telomere research. PNAs' superior resolution and precision make them a favourable choice for genetic toxicological assessments. The integration of PNAs in contemporary analytical workflows heralds a promising evolution in genetic toxicology, potentially revolutionizing diagnostics, prognostics, and therapeutic avenues. In this timely review, we attempted to assess the limitations of current PNA-FISH methodology and recommend refinements.

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

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

Unveiling the Significance of MRP 1 in Achieving Complete Remission Following Induction Therapy in Acute Myeloid Leukemia.

BACKGROUND: Increased expression of MRP 1 in AML patients results in the efflux of drugs from the cells, preventing the patient from achieving remission or potentially leading to relapse. Several studies have demonstrated that early identification of ABC transporter may yield favorable outcomes. AIMS AND OBJECTIVES: The objectives of the study were to investigate the correlation between MRP 1 gene expression and MRP 1 protein levels and the response to remission induction in AML patients. METHOD: A total of 40 AML patients were recruited from March 2021 to June 2022. Peripheral blood was collected in two tubes (yellow and purple top) to assess the MRP 1 gene and protein. For MRP 1 gene assessment, RNA was isolated from blood samples, cDNA was prepared, and qRT-PCR was performed to analyze gene expression. The relationship between the gene and complete remission was determined. Identification of MRP 1 protein was conducted using ELISA, and the relationship between protein levels and complete remission (CR) was explored. RESULTS: Most of the patients were aged between 25 and 39 years, encompassing both males and females. This study observed a clinical correlation between MRP 1 gene expression and complete remission. The findings revealed that 69.2 percent of patients with high gene expression failed to achieve complete remission, whereas the analysis of MRP 1 protein in relation to complete remission showed no statistical significance. The MRP1 gene showed high expression (66.7%) in patients with FLT3 mutation, whereas low expression of MRP1 was associated with a high occurrence (60%) of NMP1 mutation. CONCLUSION: Further comprehensive multicenter studies with larger sample sizes are required to validate the findings of this study. It is recommended to pinpoint the mechanism and regulation of MRP 1 and its interaction with other molecular pathways.