Low Blast Research Articles

New insights into the nature and classification of myelodysplastic neopmasm

The World Health Organization's (WHO) International Agency for Research on Cancer (IARC) released the fifth edition of the Classification of Tumors of the Hematopoietic and Lymphoid Tissues, renaming myelodysplastic syndrome (MDS) to myelodysplastic neoplasm (still abbreviated as MDS). This new classification integrates next-generation sequencing data to standardize the disease's nature. The name change reflects a deeper understanding of the disease, transitioning from the vague "syndrome" to a clearly defined neoplastic disease. The new classification divides MDS into two major categories: cytogenetic abnormalities and morphological abnormalities. Cytogenetic abnormalities include MDS with low blasts and isolated 5q deletion, MDS with low blasts and SF3B1 mutation, and MDS with biallelic TP53 alterations. Morphological abnormalities include MDS with low blasts, MDS with increased blasts and hypoplastic MDS. This revision provides a foundation for precise diagnosis and treatment of MDS, further restricting the application of immunosuppressive therapy and advancing genetic research in diagnostics and therapeutics.

Clinical Characteristics, Molecular Features and Transplantation Outcomes in MDS with Low Blasts and without Defining Genetic Abnormalities: An Analysis of MDS-h and MDS-LB Patients

Clinical Characteristics, Molecular Features and Transplantation Outcomes in MDS with Low Blasts and without Defining Genetic Abnormalities: An Analysis of MDS-h and MDS-LB Patients

Co-existence of Myelodysplastic Disorders and Plasma Cell Neoplasms: Case Series

Abstract Introduction/Objective The development of myelodysplastic syndrome (MDS) in patients with plasma cell neoplasm (PCN) receiving treatment is well reported. However, co-occurrence of both, without any chemotherapy history, is sparsely documented in the literature. We aim to highlight the possible association between both. Methods/Case Report Database search was done using Epic Slicer-Dicer for cases with biopsy proven co-existing MDS and PCN (from 2010-2022). The patients’ charts were reviewed to collect and analyze the clinical features. Results (if a Case Study enter NA) We identified 3 patients, all in their seventies on presentation: First patient: man, presented with unexplained chronic anemia. Serum protein electrophoresis (SPEP) showed elevated levels of monoclonal IgG kappa (4.2 g/dl). Evaluation of the BM biopsy revealed MDS with low blasts (WHO-5) with IgG plasma cell myeloma (56% Kappa-restricted plasma cells). Chromosome analysis revealed normal karyotype. Molecular studies were not done. Second patient: man, with Rheumatoid Arthritis and anemia. SPEP revealed biclonal IgG lambda (2.0 g/dl). BM biopsy indicated 5-8% lambda-restricted plasma cell proliferation. Anemia was managed with darbopoetin, but without improvement. The patient did not get chemotherapy. Follow-up BM biopsy was done, showing MDS with low blasts and ringed sideroblasts (WHO-5) alongside the PCN. FISH showed two abnormal IGH rearrangement populations. Chromosome analysis revealed normal karyotype. Molecular studies were not done. Third patient: woman, with pancytopenia. SPEP indicated monoclonal protein IgG lambda (1.8 g/dl). BM biopsy revealed 10% lambda-restricted plasma cell proliferation, coexisting with MDS with increased blasts grade 2 (WHO-5). Molecular studies showed: 2-FLT3 L601_K602insNFREYEYDL and ASXL1 E635fs*15. Chromosome analysis revealed normal karyotype. No in common clinical findings found during chart reviewing the cases. Conclusion Further investigating the underlying pathology, bone marrow microenvironment, and molecular and cytogenetics abnormalities in a larger number of patients with co-existing MDS and PCN is important. Also, if there was an association, it is important to study the sequence of occurrence between them.

Development of Low Carbon Blast Furnace Operation Technology by using Experimental Blast Furnace

Development of Low Carbon Blast Furnace Operation Technology by using Experimental Blast Furnace

Chromothripsis in myeloid malignancies.

Chromothripsis refers to massive genomic rearrangements developed during a catastrophic event. In total acute myeloid leukemia (AML), the incidence of chromothripsis ranges from 0 to 6.6%, in cases of complex karyotype AML, the incidence of chromothripsis ranges from 27.3 to 100%, whereas in cases of AML with TP53 mutations, the incidence ranges from 11.1 to 90%. For other types of malignancies, the incidence of chromothripsis also varies, from 0 to 10.5% in myelodysplastic syndrome to up to 61.5% in cases of myelodysplastic syndrome with TP53 mutations.Chromothripsis is typically associated with complex karyotypes and TP53 mutations, and monosomal karyotypes are associated with the condition. ERG amplifications are frequently noted in cases of chromothripsis, whereas MYC amplifications are not. Moreover, FLT3 and NPM1 mutations are negatively associated with chromothripsis. Chromothripsis typically occurs in older patients with AML with low leukocyte counts and bone marrow blast counts. Rare cases of patients with chromothripsis who received intensive induction chemotherapy revealed low response rates and poor overall prognosis. Signal pathways in chromothripsis typically involve copy number gain and upregulation of oncogene gene sets that promote cancer growth and a concomitant copy number loss and downregulation of gene sets associated with tumor suppression functions.Patients with chromothripsis showed a trend of lower complete remission rate and worse overall survival in myeloid malignancy. Large-scale studies are required to further elucidate the causes and treatments of the condition.

Higher prevalence of poor prognostic markers at a younger age in adult patients with myelodysplastic syndrome – evaluation of a large cohort in India

BackgroundThe karyotype is a major determinant of prognosis in myelodysplastic syndrome (MDS). Details of the cytogenetic profile of MDS in South Asia are limited because cytogenetic services are not widely available.MethodsWe performed a retrospective analysis of the cytogenetic and clinicopathologic profile of adult primary MDS seen consecutively at a tertiary-care centre in South India between 2003 and 2017. Patients were re-categorised according to the 2022 World Health Organisation (WHO) and the International Consensus classifications (ICC).ResultsThere were 936 patients aged 18–86 years (median age 53, 65% males), with MDS with del 5q, low blasts and increased blasts in 7.5%, 58.4% and 34.1% respectively. Clonal abnormalities were seen in 55% of patients, with solitary abnormalities in 29.8% and complex karyotypes (CK, ≥ 3 abnormalities) in 15%. The most frequent abnormalities were monosomy 7/deletion 7q (16.1%), deletion 5q (14.5%), trisomy 8 (11.5%), and deletion 20q (5.1%). Cytogenetic prognosis groups were distributed as follows: very good, 2%; good, 55.6%; intermediate, 16.2%; poor, 15%; very poor, 11.2%. Clinical (IPSS-R) risk stratification (842 patients) showed: very low-risk, 3.9%; low-risk, 30.9%; intermediate-risk, 24.2%; high-risk, 21%; very high-risk, 20%. Age-adjustment (IPSS-RA) raised the very low-risk group to 12.4%; the other groups decreased by 1–3% each.ConclusionThe most significant finding of this cytogenetic analysis of MDS in India is that abnormal karyotypes with poor prognosis markers including monosomy 7 and CK were more frequent than in most other reports, among patients who were overall younger. Trisomy 8, deletion 20q, the IPSS-R intermediate-risk and both high-risk groups were more common than in the West. Trisomy 8 was less common than in South-East Asia while CK and deletion 20q were comparable. Evaluation of such large cohorts highlights the unique features of MDS in different parts of the world. These findings suggest that there could be differences in predisposing factors, environmental or genetic, and emphasise the need for further exploration to better understand the varied nature of MDS.

Repetitive subconcussion results in disrupted neural activity independent of concussion history

Abstract Concussion is a public health crisis that results in a complex cascade of neurochemical changes that can have life-changing consequences. Subconcussions are generally considered less serious, but we now realize repetitive subconcussions can lead to serious neurological deficits. Subconcussions are common in contact sports and the military where certain personnel are exposed to repetitive occupational blast overpressure. Post-mortem studies show subconcussion is a better predictor than concussion for chronic traumatic encephalopathy—a progressive and fatal neurodegenerative tauopathy, only diagnosable post-mortem—thus, an in vivo biomarker would be transformative. Magnetoencephalography captures the dynamics of neuronal electrochemical action, and functional MRI shows that functional connectivity is associated with tauopathy patterns. Therefore, both imaging modalities could provide surrogate markers of tauopathy. In this cross-sectional study, we examined the effects of repetitive subconcussion on neuronal activity and functional connectivity using magnetoencephalography and functional MRI, and on neurological symptoms and mental health in a military sample. For magnetoencephalography and outcome analyses, 81 participants were split into ‘high’ and ‘low’ blast exposure groups using the generalized blast exposure value: n = 41 high blast (26.4–65.7 years; 4 females) and n = 40 low blast (28.0–63.3 years; 8 females). For functional MRI, two high blast male participants without data were excluded: n = 39 (29.6–65.7 years). Magnetoencephalography revealed disrupted neuronal activity in participants with a greater history of repetitive subconcussions, including neural slowing (higher delta activity) in right fronto-temporal lobes and subcortical regions (hippocampus, amygdala, caudate, pallidum and thalamus), and functional dysconnectivity in the posterior default mode network (lower connectivity at low and high gamma). These abnormalities were independent of concussion or traumatic stress history, and magnetoencephalography showed functional dysconnectivity not detected in functional MRI. Besides magnetoencephalography changes, those with higher blast exposure had poorer somatic and cognitive outcomes, with no blast-related differences in mental health or associations between neurological symptoms and neuronal activity. This study suggests that repetitive subconcussions have deleterious effects on brain function and that magnetoencephalography provides an avenue for both treatment targets by identifying affected brain regions and in prevention by identifying those at risk of cumulative subconcussive neurotrauma.

Deadman Behavior and Slag–Iron–Coke Interaction of Low Carbon and Safety Blast Furnace: A Review

The elucidation of the deadman's behavior and the interaction between slag–iron–coke within the blast furnace hearth are essential for the realization of low‐carbon and safe production. In this review, the macrostate of the deadman, the interactions between slag–iron–coke, carburizing behaviors, and renewal mechanisms are comprehensively examined. First, the formation and state of the deadman, voidage, and the distribution of coke sizes within the blast furnace hearth are characterized. The average coke particle size ranges from 20 to 30 mm, and the deadman void fraction of 30–50%. Second, the interaction between slag–iron–coke as well as the occurrence state of the mineral layer at the interface within the deadman is elucidated. The ash composition and content of coke are the key factors affecting the slag–iron–coke interaction and interface phase composition. Third, the influence exerted by critical factors such as the physical properties of the carbon source, molten iron, and temperature on the carburizing behavior are analyzed, with the renewal mechanisms of the deadman also being disclosed. Finally, three future focal areas are proposed: characterization and intelligent monitoring of deadman permeability, analysis of slag–iron–coke properties and interface mineral layers control, and in‐depth analysis of deadman renewal and carbon carburization in molten iron. It is anticipated that the studies will enhance the comprehension of deadman behavior and the interactions between slag–iron–coke, thereby fostering the blast furnace's sustainable development.

Reclassification of Myelodysplastic Neoplasms According to the 2022 World Health Organization Classification and the 2022 International Consensus Classification Using Open-Source Data: Focus on SF3B1- and TP53-mutated Myelodysplastic Neoplasms.

In 2022, the WHO and International Consensus Classification (ICC) published diagnostic criteria for myelodysplastic neoplasms (MDSs). We examined the influence of the revised diagnostic criteria on classifying MDSs in a large population. We retrieved an open-source pre-existing dataset from cBioPortal and included 2,454 patients with MDS in this study. Patients were reclassified based on the new diagnostic 2022 WHO and ICC criteria. Survival analysis was performed using Cox regression to validate the new criteria and to assess risk factors. Based on the 2022 WHO criteria, 1.4% of patients were reclassified as having AML. The 2022 WHO criteria provide a superior prognostic/diagnostic model to the 2017 WHO criteria (Akaike information criterion, 14,152 vs. 14,516; concordance index, 0.705 vs. 0.681). For classifying MDS with low blast counts and SF3B1 mutation, a variant allele frequency cut-off of 5% (2022 WHO criteria) and the absence of RUNX1 co-mutation (2022 ICC criteria) are diagnostically relevant. For classifying MDSs with mutated TP53, a blast count cut-off of 10% (2022 ICC criteria) and multi-hit TP53 (2022 WHO criteria) are independent risk factors in cases with ≥10% blasts. Our findings support the refinements of the new WHO criteria. We recommend the complementary use of the new WHO and ICC criteria in classifying SF3B1- and TP53-mutated MDSs for better survival prediction.

Flow cytometry in the differential diagnosis of myelodysplastic neoplasm with low blasts and cytopenia of other causes.

Myelodysplastic neoplasms (MDS) are characterized by cytopenia, morphologic dysplasia, and genetic abnormalities. Multiparameter flow cytometry (FCM) is recommended in the diagnostic work-up of suspected MDS, but alone is not sufficient to establish the diagnosis. Our aim was to investigate the diagnostic power of FCM in a heterogeneous population of patients with cytopenia, excluding cases with increased blast count. We analyzed bone marrow samples from 179 patients with cytopenia (58 MDS, 121 non-MDS) using a standardized 8-color FCM method. We evaluated the sensitivity, specificity, and accuracy of several simple diagnostic approaches, including Ogata score, extended Ogata score, the WHO and ELN iMDSFlow recommended "3 aberrations in two cell compartments method," and the combination of the Ogata score and "3 aberrations in two cell compartments method." The patients were followed until the diagnosis was confirmed, with a median follow-up of 2months (range 0.2-27). The combination of Ogata score and "3 aberrations in two cell compartments method" achieved the highest diagnostic accuracy (78%) with sensitivity and specificity 61% and 86%, respectively. When using only the "3 aberrations in two cell compartments method," the accuracy was 77% with a sensitivity of 72% and a specificity of 79%. The most frequently observed etiologies among the false positive cases were substrate deficiencies, inflammation/infection, or toxic effects. MDS can be excluded in all these cases after a thorough clinical evaluation and a relatively short follow-up. FCM remains an important but supplementary part in an integrated diagnostic process of MDS with low blasts. The combination of the Ogata score and the "3 aberrations in two cell compartments method" slightly improves accuracy compared to the detection of "3 aberrations in two cell compartments method" alone.

Guideline for treating relapsed or refractory myeloid leukemia in children with Down syndrome.

Treatment of relapsed and refractory myeloid leukemia in Down syndrome (r/r ML-DS) poses significant challenges, as prognosis is dire and there is no established standard treatment. This guideline provides treatment recommendations based on a literature review and collection of expert opinions, aiming to improve overall and event-free survival of patients. Treatment options include fludarabine and cytarabine (FLA)±gemtuzumab ozogamicin (GO), azacytidine (AZA)±panobinostat, and hematopoietic stem cell transplantation (HSCT). Preferred approaches are AZA±panobinostat for cases with low blast count or FLA±GO for cases with high blast count, followed by HSCT after remission. Further research is crucial for the investigation of targeted therapies (e.g., BH3 mimetics, LSD1, JAK inhibitors).

Real-world study of the use of azacitidine in myelodysplasia in Australia.

Hypomethylating agents are the most widely used upfront therapy for patients with myelodysplastic syndrome (MDS) who are not suitable for hematopoietic stem cell transplantation. In Australia, azacitidine was, until recently, the only approved and subsidized treatment for patients with intermediate-2 and high-risk MDS, chronic myelomonocytic leukemia, and low blast acute myeloid leukemia. We analyzed prescription data to evaluate the real-world persistence and overall survival (OS) of patients prescribed azacitidine for the first time in Australia. A retrospective cohort analysis of patients who had been prescribed Pharmaceutical Benefits Scheme (PBS)-listed azacitidine for the first time, between January 2016 and April 2021, was conducted using the PBS 10% dataset. Treatment persistence and OS were estimated using Kaplan-Meier methods. The impact of the number of treatment cycles and treatment adherence on OS was also estimated. There were 351 patients in the PBS 10% dataset who initiated treatment with azacitidine. The average age (standard deviation [SD]) at azacitidine initiation was 71.9 (11.1) years and the average number (SD) of azacitidine prescriptions was 5.6 (0.2). The median persistence on azacitidine was 15.6 months, and the OS was 13.4 months. The median OS for patients who had six or more cycles of azacitidine treatment was greater compared to patients who had five or less cycles of treatment. The data from this real-world study illustrate the unmet medical needs of patients with MDS treated with azacitidine in Australia. The majority of patients are not treated with the optimal number of cycles of azacitidine, which is negatively correlated with patient outcomes.

Prognostic impact of the conditioning intensity on outcomes after allogeneic transplantation for MDS with low blasts: a nationwide retrospective study by the adult MDS working group of the Japan Society for Transplantation and Cellular Therapy.

Poor prognostic factors, such as transfusion dependency and chromosomal risk, need to be considered in the indication of allogeneic hematopoietic cell transplantation (allo-HCT) for patients harboring myelodysplastic syndromes with less than 5% marrow blasts (MDS-Lo). We analyzed the post-transplant outcomes of 1229 MDS-Lo patients who received myeloablative (MAC)(n = 651), reduced-intensity (RIC)(n = 397), and non-myeloablative conditioning (NMAC) regimens (n = 181). The multivariate analysis revealed that the RIC group had better chronic graft-versus-host disease (GVHD)- and relapse-free survival (CRFS) (P = 0.021), and GVHD- and relapse-free survival (GRFS) than the MAC group (P = 0.001), while no significant differences were observed between the NMAC and MAC groups. In the subgroup analysis, the MAC group has better overall survival (P = 0.008) than the RIC group among patients with an HCT-comorbidity index (HCT-CI) score of 0, while the RIC group had better overall survival (P = 0.029) than the MAC group among those with an HCT-CI score ≥3. According to the type of conditioning regimen, total body irradiation 12 Gy-based MAC regimen showed better OS and CRFS than the other MAC regimen, and comparable outcomes to the RIC regimen. In conclusion, the RIC and NMAC regimens are promising options for MDS-Lo patients in addition to the MAC regimen.

Prolidase Enzyme Activity as a Potential Biomarker for Blast-Induced Traumatic Brain Injury: A Study in a Rat Model

AbstractBlast-induced traumatic brain injury (TBI) poses a significant threat to individuals exposed to explosive events. We hypothesized that blast-induced neurotrauma is an oxidative stress to brain and hence prolidase (PD) enzyme, which is an antioxidant is recommended; its serum levels are better markers of degree of injury in the acute phase for TBI in a rat blast injury model. Results revealed that PD enzyme activity in the hippocampus showed a slight increase across high, medium, and low blast pressures, but remained lower than the sham group. However, serum PD enzyme activity levels were significantly higher in the blast-exposed groups compared to the sham group. Tau protein levels were significantly elevated in the blast-exposed groups. Longitudinal analysis demonstrated a decline in hippocampal PD activity over time, while tau protein levels progressively increased, suggesting a shift from initial oxidative stress to neurodegeneration. These findings suggest that blast injury triggers oxidative stress and subsequent neurodegenerative processes. The correlation with tau protein levels further supports the involvement of oxidative stress in neurodegeneration. In conclusion, this study provides insights into the underlying pathophysiological mechanisms of blast-induced TBI and highlights the potential utility of PD enzyme activity as a diagnostic marker.

Cumulative Blast Impulse Is Predictive for Changes in Chronic Neurobehavioral Symptoms Following Low Level Blast Exposure during Military Training.

Cumulative low-level blast exposure during military training may be a significant occupational hazard, increasing the risk of poor long-term outcomes in brain function. US Public Law 116-92 section717 mandates that US Department of Defense agencies document the blast exposure of each Service member to help inform later disability and health care decisions. However, which empirical measures of training blast exposure, such as the number of incidents, peak overpressure, or impulse, best inform changes in the neurobehavioral symptoms reflecting brain health have not been established. This study was approved by the US Army Special Operations Command, the University of North Carolina at Chapel Hill, and the VA Puget Sound Health Care System. Using methods easily deployable across different organizational structures, this study sought to identify and measure candidate risk factors related to career occupational blast exposure predictive of changes in neurobehavioral symptom burden. Blast dosimetry-symptom relationships were first evaluated in mice and then tested in a military training environment. In mice, the righting time neurobehavioral response was measured after exposure to a repetitive low-level blast paradigm modeled after Special Operations training. In the military training environment, 23 trainees enrolled in a 6-week explosive breaching training course, 13 instructors, and 10 Service member controls without blast exposure participated in the study (46 total). All participants provided weekly Neurobehavioral Symptom Inventory (NSI) surveys. Peak blast overpressure, impulse, total number of blasts, Time in Low-Level Blast Occupation, and Time in Service were analyzed by Bayesian analysis of regression modeling to determine their probability of influence on the post-training symptoms reported by participants. We tested the hypothesis that cumulative measures of low-level blast exposure were predictive of changes in neurobehavioral symptoms. In mice, repetitive blast resulted in reduced righting times correlated with cumulative blast impulse. In Service members, peak blast overpressure, impulse, total number of blasts, Time in Low-Level Blast Occupation, and Time in Service all showed strong evidence of influence on NSI scores after blast exposure. However, only models including baseline NSI scores and cumulative blast impulse provided significant predictive value following validation. These results indicate that measures of cumulative blast impulse may have utility in predicting changes in NSI scores. Such paired dosimetry-symptom measures are expected to be an important tool in safely guiding Service members' occupational exposure and optimizing force readiness and lethality.

Study protocol: Identifying transcriptional regulatory alterations of chronic effects of blast and disturbed sleep in United States Veterans.

Injury related to blast exposure dramatically rose during post-911 era military conflicts in Iraq and Afghanistan. Mild traumatic brain injury (mTBI) is among the most common injuries following blast, an exposure that may not result in a definitive physiologic marker (e.g., loss of consciousness). Recent research suggests that exposure to low level blasts and, more specifically repetitive blast exposure (RBE), which may be subconcussive in nature, may also impact long term physiologic and psychological outcomes, though findings have been mixed. For military personnel, blast-related injuries often occur in chaotic settings (e.g., combat), which create challenges in the immediate assessment of related-injuries, as well as acute and post-acute sequelae. As such, alternate means of identifying blast-related injuries are needed. Results from previous work suggest that epigenetic markers, such as DNA methylation, may provide a potential stable biomarker of cumulative blast exposure that can persist over time. However, more research regarding blast exposure and associations with short- and long-term sequelae is needed. Here we present the protocol for an observational study that will be completed in two phases: Phase 1 will address blast exposure among Active Duty Personnel and Phase 2 will focus on long term sequelae and biological signatures among Veterans who served in the recent conflicts and were exposed to repeated blast events as part of their military occupation. Phase 2 will be the focus of this paper. We hypothesize that Veterans will exhibit similar differentially methylated regions (DMRs) associated with changes in sleep and other psychological and physical metrics, as observed with Active Duty Personnel. Additional analyses will be conducted to compare DMRs between Phase 1 and 2 cohorts, as well as self-reported psychological and physical symptoms. This comparison between Service Members and Veterans will allow for exploration regarding the natural history of blast exposure in a quasi-longitudinal manner. Findings from this study are expected to provide additional evidence for repetitive blast-related physiologic changes associated with long-term neurobehavioral symptoms. It is expected that findings will provide foundational data for the development of effective interventions following RBE that could lead to improved long-term physical and psychological health.

UBTF tandem duplications in pediatric myelodysplastic syndrome and acute myeloid leukemia: implications for clinical screening and diagnosis.

Recent genomic studies in adult and pediatric acute myeloid leukemia (AML) demonstrated recurrent in-frame tandem duplications (TD) in exon 13 of upstream binding transcription factor (UBTF). These alterations, which account for approximately 4.3% of AML in childhood and about 3% in adult AML aged <60 years of age, are subtype-defining and associated with poor outcomes. Here, we provide a comprehensive investigation into the clinicopathological features of UBTF-TD myeloid neoplasms in childhood, including 89 unique pediatric AML and 6 myelodysplastic syndrome (MDS) cases harboring a tandem duplication in exon 13 of UBTF. We demonstrate that UBTF-TD myeloid tumors are associated with dysplastic features, low bone marrow blast infiltration, and low white blood cell count. Furthermore, using bulk and single-cell analyses, we confirm that UBTF-TD is an early and clonal event associated with a distinct transcriptional profile, whereas the acquisition of FLT3 or WT1 mutations is associated with more stem cell-like programs. Lastly, we report rare duplications within exon 9 of UBTF that phenocopy exon 13 duplications, expanding the spectrum of UBTF alterations in pediatric myeloid tumors. Collectively, we comprehensively characterize pediatric AML and MDS with UBTF-TD, and highlight key clinical and pathologic features that distinguish this new entity from other molecular subtypes of AML.

Myelodysplastic syndromes del(5q): Pathogenesis and its therapeutic implications.

Myelodysplastic syndromes (MDS) encompass a heterogeneous set of acquired bone marrow neoplastic disorders characterized by ineffective hematopoiesis within one or more bone marrow lineages. Nearly half of MDS patients carry cytogenetic alterations, with del(5q) being the most prevalent. Since its first description, del(5q) was consistently correlated with a typical clinical phenotype marked by anemia, thrombocytosis, and a low risk of evolving into acute leukemia. Presently, the World Health Organization (WHO) classification of myeloid neoplasms recognizes a specific subtype of MDS known as "myelodysplastic neoplasm with low blast and isolated del(5q)" identified by the sole presence of 5q deletion or in combination with one other abnormality excluding -7/del(7q). Several studies have sought to unravel the biological processes triggered by del(5q) in the development of MDS, revealing the involvement of various genes localized in specific regions of chromosome 5 referred to as common deleted regions (CDR). This intricate biological landscape makes the MDS cells with del(5q) exceptionally sensitive to lenalidomide. Several studies have confirmed the efficacy of lenalidomide in this context. Regrettably, the response to lenalidomide is not conclusive, prompting ongoing research into biological mechanisms that drive patients toward leukemia and strategies to circumvent lenalidomide resistance and disease progression.

Risk Factors and Prognosis of Chronic Myeloid Leukemia in Saudi Arabia: A Systematic Review

Background: Among adult leukaemias, chronic myeloid leukaemia (CML) is one of the most prevalent types. The Philadelphia chromosome, which constitutively activates tyrosine kinase through the BCR-ABL1 oncoprotein, is central to the pathophysiology of CML.&#x0D; Objectives: To study the risk factors and prognosis of chronic myeloid leukemia in Saudi Arabia.&#x0D; Methods: PubMed, SCOPUS, Web of Science, and Science Direct were systematically searched for relevant literature. Rayyan QRCI was employed throughout this comprehensive process.&#x0D; Results and Interpretation: seven studies with a total of 658 patients and 357 (54.3) were males. Risk factors for the development of CML were shown to be limited to younger and middle-aged groups, with a slight male predominance. This study showed that imatinib for CML has both long-term efficacy and manageable side effects. Improved compliance, lower blast and basophil counts, increased haemoglobin, increased platelets, and a low-risk score were all associated with different molecular reactions to imatinib. Future research is required to assess the possible risk factors, management lines, and prognostic factors of CML in Saudi population.

A Rare Case of Plasma Cell Myeloma, Myelodysplastic Neoplasm with Low Blast and SF3B1 Mutation and Dyserythropoiesis with Ring Sideroblasts

Myelodysplastic syndromes (MDS) are heterogeneous hematological neoplasms which lead to dysplasia, cytopenia and hematopoiesis. They have a risk of transforming into Acute Myeloid Leukemia (AML) in some cases. Genetic markers that are determined by cytogenetics, SNP-A karyotyping and molecular mutations have evolved to define conditions of pathogenesis and risk evaluation for the development of AML. Among the concerned are the mutations of the spliceosome (SF3B1, SRSF2, ZRSR2 and U2AF1) epigenetic mutations (DNMT3A, EZH2) and also mutations in transcription factors (RUNX1) and tyrosine kinases (N-RAS, K-RAS). Here, we report a case of an 80-year-old female patient presented for the evaluation of myeloma. A morphology report shows changes that suggest multiple myeloma. Lab data shows anemia, elevated creatinine and calcium; CBC revealed mild neutrophilic leukocytosis and microcytic anemia. Bone marrow demonstrated approximately 50-60% involvement by a plasma cell infiltrate; there was mild dysgranulopoiesis and dyserythropoiesis which are suggestive of plasma cell myeloma. Frequent mutations in MDS and overlap syndromes were discovered due to advances in genomic studies. The differential diagnosis of MDS is challenging because they overlap the disorders sharing features of other illnesses. It is expected that more research on MDS and overlapping disorders will highlight the roles of mutations as “therapeutic targets” and “prognostic indicators”.