Abstract:

Background/Objectives: Chronic lymphocytic leukemia (CLL) is characterized by genetic and epigenetic alterations. This study aimed to assess the methylation status of E-Cadherin and MMP-9 gene promoters and to explore their relationships with disease pathogenesis and hematological parameters in CLL patients. Methods: A case–control study was conducted including 70 newly diagnosed CLL patients and 70 age- and sex-matched healthy controls. Promoter methylation of E-Cadherin and MMP-9 genes was evaluated using methylation-specific PCR (MSP) and methylation-sensitive restriction enzyme PCR (MSRE-PCR), respectively. Results: The median patient age was 62 years, and 68.5 % were males. Binet stage A was the most common (57.3 %). E-Cadherin promoter methylation was detected in 75.7 % of CLL patients and 77.1 % of controls (p = 0.91), showing no significant association with disease occurrence, however, it showed a significant correlation with higher lymphocyte counts (p = 0.01). In contrast, MMP-9 promoter methylation was significantly less frequent in CLL cases (70.0 %) than in controls (100 %, p = 0.001). Unmethylated MMP-9 correlated significantly with female gender (p = 0.02), lower hemoglobin (p = 0.031), and reduced platelet counts (p = 0.001) and higher lymphocytes counts (p = 0.035). Conclusion: MMP-9 promoter hypomethylation may play a pathogenic role in CLL and is associated with female gender and cytopenia, whereas E-Cadherin methylation appears non-specific. MMP-9 methylation status could therefore serve as a potential biomarker for CLL biology and prognosis.

Abstract: Objective: This study aimed to analyze the demographic characteristics, clinical preliminary diagnoses, biopsy indications, and histopathological findings of adult bone marrow biopsies to construct a framework that aids clinicians and pathologists in evaluating bone marrow biopsy results. Materials and Methods: Bone marrow biopsy reports from 900 cases referred to the Department of Internal Diseases Hematology at Afyonkarahisar Health Sciences University from January 1, 2017, to December 31, 2021, were retrospectively analyzed. Patients with insufficient material (18) and those sent for treatment response evaluation (184) were excluded, resulting in 698 patients being included in the study. Data analysis was performed using SPSS v26, employing the McNemar test to assess clinicopathological concordance, with a significance level set at p< 0.05. Results: Of the 698 patients analyzed, 388 (55.6%) were male and 310 (44.4%) were female, with ages ranging from 18 to 87 years. The most common indications for biopsy were lymphoma (16.09%), pancytopenia (16.05%), and anemia with a high sedimentation rate (14.06%). The most frequently noted preliminary diagnosis was myeloma (22.02%), followed by lymphoma (16.09%) and acute leukemia (10.03%). Significant clinicopathological concordance was observed in diagnoses such as aplastic anemia and lymphoplasmacytic lymphoma, whereas discordance was noted in conditions such as follicular lymphoma and acute myeloid leukemia (AML), reflecting the complexity and challenge of accurate diagnosis in hematologic conditions. Conclusion: This study documented a high incidence of lymphoma and myeloma as preliminary diagnoses, with myeloma confirmed in 52% of cases with an initial suspicion based on clinical presentation. Notable discrepancies between clinical suspicion and histopathological findings were evident in conditions such as follicular lymphoma and acute myeloid leukemia (AML), with a significant discordance rate. These findings highlight the need for enhanced diagnostic precision and the development of sophisticated diagnostic algorithms to improve the predictive accuracy of preliminary clinical diagnoses. Ultimately, this study calls for a refined approach to the clinical and pathological evaluation of bone marrow biopsies to better support therapeutic decision making and patient management.

Abstract: Sex-based variations are significant among the major subtypes of leukemia. This review briefly discusses the current understanding and knowledge gaps related to sex differences in epidemiology; mortality and survival rates; risk factors, and epigenetic, metabolomic, and sex-specific patterns. Males have higher incidence rates and mortality rates of leuke-mia than females do, highlighting the significance of biological and epidemiologic factors. Sex-based differences were reported in only 0.5% of the clinical trials, an underreporting may be resulting from a persistent lack of awareness or prioritization of integrating sex as a significant variable in research findings. Interesting sex-based patterns arise that sub-stantially impact disease epidemiology. An intriguing medical enigma in leukemia is treatment response, where women have higher overall survival rates but more severe treatment-related toxicity. However, ALL in pediatric patients contradicts this enigma, suggesting that gender differences may be less pronounced during childhood when hor-monal levels are low. Sex-based risk factors are discussed at both the environmental and genetic levels where epigenetic variations, such as DNA methylation, affect gene expres-sion differently in males versus females. Hematological and biochemical patterns are shown from a sex-based perspective in this review. Furthermore, there are clear signs of sex-based differences in the recognition of various metabolites in males and females, which could support the foundation for future research. We encourage researchers not only to perform sex-stratified analyses in their ongoing studies but also to design sex-based clinical trials.

Abstract: Immunothrombosis can affect substantially the course and outcomes of severe infections and immune-mediated diseases. While inflammatory thrombi are neutrophil-rich, impact of neutrophils on clot contraction, a key modulator of thrombus stability and obstructiveness, was unknown. This study investigated how neutrophils and neutrophil extracellular traps (NETs) affect the rate and extent of platelet-driven clot contraction. Isolated human neutrophils were activated with phorbol-12-myristate-13-acetate (PMA) to induce NETosis, confirmed by fluorescence microscopy and scanning electron microscopy. Thrombin-induced clots, formed from whole blood or platelet-rich plasma, were supplemented with non-activated or PMA-activated neutrophils. Clot contraction kinetics and viscoelasticity were analyzed. PMA-activated neutrophils significantly enhanced the rate and final extent of clot contraction compared to controls. This promoting effect was abolished by DNAse I, confirming that it was mediated by NETs embedded in the fibrin network. The factor Xa inhibitor rivaroxaban also abrogated this effect, indicating a role for NET-induced endogenous thrombin generation and platelet hyperactivation. Thromboelastography revealed that NETs made clots softer and more deformable. We conclude that activated neutrophils promote clot contraction via NETs embedded into the fibrin network, which enhance platelet contractility via endogenous thrombin production and increase clot deformability, suggesting that inflammatory thrombosis may require treatments addressing this enhanced contractility.

Abstract: Gastric cancer has historically relied on cytotoxic chemotherapy, yet its considerable mo lecular heterogeneity has limited therapeutic efficacy. The development of anti-body-mediated therapies has marked a new era in precision oncology, enabling selective targeting of biomarkers such as HER2, VEGFR2, PD-1/PD-L1, and CLDN18.2. This review summarizes the evolution of antibody-based strategies in gastric cancer, beginning with trastuzumab, the first HER2-targeted treatment, followed by the decade-long stagnation after the failure of T-DM1, and the recent establishment of trastuzumab deruxtecan (T-DXd) as a new standard of care. We further examine advances in anti-angiogenic therapy with ramucirumab, the incorporation of immune checkpoint inhibitors such as nivolumab and pembrolizumab into first-line regimens, and the clinical validation of CLDN18.2, culmi-nating in the approval of zolbetuximab. Emerging modalities—including next-generation antibody–drug conjugates (ADCs), bispecific antibodies, TROP2-directed agents, and CLDN18.2-targeted CAR-T cells—are also discussed. Finally, key challenges such as treatment resistance, real-time biomarker monitoring, and optimal sequencing in mul-ti-biomarker–positive patients are explored. Collectively, antibody-mediated therapy con-tinues to shift gastric cancer management toward increasingly personalized and durable treatment strategies.

Abstract: Background/Objectives: Sickle cells disease (SCD) and -thalassemia are autosomal recessive disorders of erythroid cells due to gene mutations occurring at the level of the -globin gene. The severe forms of these hemoglobinopathies observed in individuals homozygous for these defective genes need intensive treatments, are associated with a poor quality of life and allogeneic hematopoietic stem cell represents the only curative treatment option that can be offered only to a limited proportion of patients. Methods: This work is a narrative review supported by a systematic literature search and analysis. Results: To bypass this limitation, autologous hematopoietic stem cell transplantation has been developed in these patients in which patients’ HSCs are harvested and genetically modified ex vivo, then transplanted back into patients after conditioning for stem cell transplantation. There are two different approaches for gene therapy of hemoglobinopathies’, one based on gene addition or gene silencing using lentiviruses as vectors and the other based on gene editing strategies using CRISPR-Caspase 9 technology or base editing. Several gene therapy products have been successfully evaluated in these patients achieving transfusion independence and correction of hematological abnormalities durable in the time. Conclusions Several gene therapy products have been approved for the treatment of SCD and -thalassemic patients and offer a potentially curative treatment for these patients.

Abstract: Diffuse large B-cell lymphoma (DLBCL) is the most common and clinically aggressive subtype of non-Hodgkin lymphoma (NHL). Although novel therapeutic agents, in-cluding rituximab and polatuzumab vedotin, have improved outcomes, almost one-third of patients ultimately develop relapsed or refractory disease. MicroRNAs (miRNAs), a class of endogenous single-stranded RNAs approximately 22 nucleotides in length, play a pivotal role in the regulation of gene expression at the post-transcriptional level through interactions with complementary target RNAs and contribute significantly to the de-velopment, progression, and treatment response of DLBCL. Oncogenic miRNAs, such as miR-155, miR-21, and the miR-17–92 cluster, promote proliferation, survival, immune evasion, and therapy resistance by modulating pathways including PI3K/AKT, NF-κB, and MYC. Conversely, tumor-suppressive miRNAs such as miR-34a, miR-144, miR-181a, and miR-124-3p inhibit oncogene activity and enhance apoptosis, with their loss often associated with adverse outcomes. Among these, miR-155 and miR-21 are particularly well studied, playing central roles in both tumor progression and remodeling of the tumor microenvironment. This review summarizes current evidence on the biological and clinical relevance of miRNAs in DLBCL, emphasizing their diagnostic and prognostic potential.

Abstract:

Background: Autologous stem cell transplantation (ASCT) remains a cornerstone in the management of multiple myeloma (MM). However, the optimal timing of ASCT and the factors determining whether patients ultimately undergo transplantation remain unclear in real-world practice. The Revised Myeloma Comorbidity Index (R-MCI) was developed to quantify patient fitness but its influence on transplant eligibility and timing has not been fully characterized. Methods: We conducted a retrospective single-center study including 137 patients with newly diagnosed MM between 2015 and 2025. Clinical parameters recorded at diagnosis included age, sex, performance status, renal and pulmonary function, cytogenetic risk, International Staging System (ISS) stage, and bone marrow plasma cell infiltration. The R-MCI was calculated for all patients [1]. Transplant timing was categorized as early (≤12 months) or delayed (>12 months) after diagnosis. Logistic regression analyses were performed to identify predictors of ASCT eligibility and timing. Results: ASCT was performed in 61 patients (44.5%). Transplanted patients were significantly younger (<65 years: 82.0% vs. 25.0%, p<0.001) and had lower R-MCI scores (median 0 vs. 1, p<0.001) compared with nontransplanted patients, while plasma cell infiltration and ISS stage did not differ. Among transplanted patients, 42.6% underwent early ASCT. In multivariate analysis, R-MCI was the only variable showing a trend toward predicting early transplantation (OR 0.27, 95% CI 0.07–1.06, p=0.06). Conclusions: In real-world MM management, patients quantified by R-MCI appear to play a more prominent role than disease burden in determining both eligibility for and timing of ASCT. Incorporating comorbidity indices alongside ISS may enhance individualized transplant decisionmaking and optimize treatment outcomes.

Abstract:

Acute chest syndrome (ACS) is a life-threatening complication of sickle cell disease (SCD) with complex infectious and non-infectious etiologies. Bacterial pathogens, including Streptococcus pneumoniae, Haemophilus influenzae, and atypical organisms such as Mycoplasma pneumoniae, play crucial roles in ACS pathogenesis, particularly in immunocompromised SCD patients with functional asplenia. Despite the importance of infectious triggers, regional data on pathogen identification rates and antimicrobial management strategies in ACS remain limited, especially from high-prevalence SCD regions. This study aimed to investigate the infectious etiologies, pathogen identification patterns, and antimicrobial management outcomes of ACS in adult SCD patients in Eastern Saudi Arabia. A five-year retrospective analysis was conducted on adult patients (≥14 years old) with SCD who were admitted with ACS to Dammam Medical Complex between 2018 and 2022. Comprehensive microbiological evaluation included blood cultures, sputum cultures, and atypical pathogen testing (Mycoplasma pneumoniae, Chlamydia pneumoniae). Data on antimicrobial regimens, pathogen identification rates, vaccination status against encapsulated bacteria, and clinical outcomes were systematically analyzed. Empirical antibiotic strategies and their effectiveness in this immunocompromised population were evaluated. A total of 60 adult SCD patients experiencing 80 episodes of ACS were included. Despite comprehensive microbiological workup, specific infectious pathogens were identified in only 8 (10.0%) episodes, highlighting the complex multifactorial etiology of ACS. Blood cultures yielded pathogens in 5 (6.3%) cases, sputum cultures in 4 (5.0%) cases, and Mycoplasma pneumoniae was identified in 3 (3.8%) episodes. All patients received empirical broad-spectrum antimicrobial therapy, with ceftriaxone and azithromycin combination being the most frequent regimen 76 (95.0%), providing coverage for both typical and atypical bacterial pathogens. Antibiotic escalation was required in 16 (20.0%) episodes. Vaccination rates against Streptococcus pneumoniae were suboptimal at 30 (50.0%), representing a significant risk factor for invasive bacterial infections in this functionally asplenic population. The intensive care unit (ICU) admission rate was 15 (18.8%), and in-hospital mortality was 3 (3.8%), with infectious complications contributing to severe outcomes. In this cohort of adult SCD patients, ACS demonstrated low rates of specific pathogen identification despite systematic microbiological investigation, supporting the multifactorial infectious and non-infectious etiology of this syndrome. The predominant use of broad-spectrum antimicrobial therapy targeting both typical and atypical bacterial pathogens proved effective in this immunocompromised population. However, suboptimal vaccination rates against encapsulated bacteria represent a critical gap in infection prevention strategies. These findings emphasize the importance of empirical antimicrobial coverage for suspected bacterial pathogens in ACS management and highlight the urgent need for enhanced vaccination programs to prevent infectious complications in functionally asplenic SCD patients.

Abstract: Background: Mediastinal gray zone lymphoma (MGZL) is a rare B-cell lymphoma which shares clinicopathologic and molecular features between primary mediastinal B-cell lymphoma (PMBL) and classical Hodgkin lymphoma (CHL). Although included as provisional disease entity back in 2008 WHO classification after initial description in 1998, the concept of MGZL has since evolved, with latest WHO-HEMA5 and ICC limiting the entity to EBV-negative mediastinal lesion. Methods: This review summarizes the historical evolution, epidemiology, clinicopathologic characteristics, immunophenotypic and genetic features, diagnostic challenges, and therapeutic strategies for MGZL. Data from retrospective series, prospective cohorts, and recent molecular studies are synthesized to provide a comprehensive perspective. Results: MGZL generally affects young adults, especially males, and presents with bulky mediastinal disease. Transitional morphology, pleomorphic Reed–Sternberg–like cells, and variable B-cell and activation markers make its diagnosis challenging. Molecular studies have shown that they share changes with PMBL and CHL such as 9p24. 1 (JAK2/PD-L1/PD-L2); however, specific alterations, including HOXA5 hypomethylation and MYC gains, argue for its designation as a separate entity. Therapeutically, DA-EPOCH-R is one of the most effective regimens, but prognosis is still worse than PMBL or CHL, 5-year OS ~40–60%. Salvage chemotherapy and autologous transplantation are frequently necessary for relapsed/refractory disease. Novel therapies, especially brentuximab vedotin and PD-1 inhibitors, appear to be effective, especially in combination. Conclusion: MGZL continues to be a diagnostically challenging, and therapeutically complex lymphoma with an inferior prognosis compared to related entities. Advancements in molecular profiling and immunotherapy suggest the promise of personalized therapy. Yet, prospective clinical trials and international cooperation are urgently needed to develop guidelines for therapy of this rare lymphoma.

Abstract: Mesenchymal stem/stromal cells (MSCs) exhibit broad differentiation capability and strong immunoregulatory potential mediated through intercellular communication and the release of diverse paracrine mediators. These features render MSCs a promising therapeutic option for managing complications associated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). This review provides an updated synthesis of MSC biology, their bidirectional interaction with immune cells, and their functional contribution to the hematopoietic niche. It also evaluates current clinical evidence regarding the therapeutic roles of MSCs and MSC-derived extracellular vesicles (EVs) in acute and chronic graft-versus-host disease (aGVHD/cGVHD) as well as in poor graft function. Mechanistic insights encompass macrophage polarization toward an anti-inflammatory phenotype, inhibition of dendritic cell maturation, enhancement of regulatory T-cell expansion, and modulation of cytokine signaling pathways. Within the bone marrow milieu, MSCs contribute to stromal restoration and angiogenic repair. Data from phase II/III clinical trials and real-world cohorts in steroid-refractory aGVHD consistently confirm the safety of MSC therapy, although response rates vary—typically higher in pediatric patients and when administered early—while survival outcomes remain inconsistent. For poor graft function, limited prospective studies indicate hematopoietic recovery following third-party MSC infusions, and combination approaches such as co-administration with thrombopoietin receptor agonists are under investigation. MSC-derived EVs emulate many immunomodulatory effects of their parental cells with a potentially safer profile, though clinical validation remains in its infancy. MSC-oriented interventions hold substantial biological and therapeutic promise, offering a favorable safety margin; however, clinical translation is hindered by product variability, suboptimal engraftment and persistence, and inconsistent efficacy across studies. Future directions should emphasize standardized manufacturing and potency assays, biomarker-driven patient and timing selection, optimized conditioning and dosing strategies, and the systematic appraisal of EV-based or genetically modified MSC products through controlled trials.

Abstract: Indolent lymphoproliferative diseases or disorders (LPD) derived from T cells or Natural Killer (NK) cells may be neoplastic or non-neoplastic, which are often difficult to distinguish from each other and from the aggressive counterparts. The etiology and pathogenesis are mostly nebulous and may be related to infections or immune dysfunction. Indolent lymphomas differ from the high-grade aggressive counterparts by a prolonged clinical course of persistent or relapsing disease, histology, immunophenotype and genetics. In the recent decades, indolent lymphomas or LPD of T or NK cell derivation have been increasingly recognized, causing diagnostic and nosologic confusion. The issue is particularly challenging in the arena of indolent intestinal lymphomas and LPD, as evidenced by the myriad of names given to the indolent intestinal T- and NK-cell lymphomas and LPD. Confounding the picture are also reports of Epstein-Barr virus (EBV)-positivity in various indolent non-intestinal LPD and rarely even in indolent intestinal T-cell lymphoma, which have been widely accepted to be typically EBV-negative. This review aims to curate current information and understanding of these diseases with the goal to resolve these issues. The recently described indolent T-lymphoblastic proliferation (iTLBP) and the re-classified indolent primary cutaneous CD4-positive small or medium T-cell LPD and primary cutaneous acral CD8-positive T-cell LPD also require greater awareness and recognition. It is important to diagnose these indolent entities in order to avoid over-treatment and unnecessary therapeutic intervention, and to provide for accurate prognostic prediction and appropriate follow up.

Abstract: We describe a patient with post-essential thrombocythemia myelofibrosis treated with intermittent hydroxyurea (Hu) therapy (20mg/Kg, given as a single dose, thrice weekly), achieving sustained disease control and regression of bone marrow fibrosis; and, discuss the efficacy of and rationale for use of intermittent Hu therapy in patients with myeloproliferative neoplasms, including those deemed to be Hu-resistant or intolerant on the commonly used continuous therapy.

Abstract: Leukemia encompasses heterogeneous hematologic malignancies characterized by dysregulated hematopoiesis, metabolic reprogramming, and therapy resistance, with relapse driven by persistent leukemic stem cells (LSCs). This comprehensive review delineates the pivotal role of the taurine–TauT (SLC6A6) axis as a metabolic vulnerability across acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), and chronic lymphocytic leukemia (CLL). Taurine, a sulfur-containing β-amino acid, modulates redox homeostasis via taurine chloramine (TauCl) formation, stabilizes mitochondrial tRNA uridine modifications for oxidative phosphorylation (OXPHOS), and regulates calcium fluxes and apoptosis. SLC6A6-mediated taurine uptake is upregulated in leukemic blasts and LSCs, correlating with adverse cytogenetics (e.g., FLT3-ITD, TP53 mutations), chemoresistance to cytarabine, doxorubicin, methotrexate, vincristine, tyrosine kinase inhibitors (TKIs), and BCL2 inhibitors (venetoclax), and minimal residual disease persistence in hypoxic bone marrow niches. Transcriptomic analyses from TCGA, BeatAML, and TARGET cohorts substantiate SLC6A6 as a prognostic biomarker. Therapeutic strategies, including selective SLC6A6 inhibition and chemosensitization, exploit this dependency to amplify ROS-induced apoptosis and eradicate LSCs, potentially enhancing remission durability. Future directions emphasize structure-guided inhibitor development and integrative metabolomic profiling for precision oncology.

Abstract:

Background/Objectives: Mechanisms underlying treatment resistance in hematopoietic malignancies such as acute lymphoblastic leukemia (ALL) include: 1) enhanced activity of anticancer drug efflux mechanisms (MRP1); 2) suppressed activity of anticancer drug influx mechanisms (ENT-1); 3) enhanced drug detoxification activity (AKR1B10, AKR1C3, CYP3A4); 4) influence of the tumor microenvironment (GRP94) etc. We conducted this study to comprehensively and clinically examine treatment resistance due primarily to a decrease in the tumor intracellular anticancer drug concentrations. Methods: (1) Case report: The subjects were 19 ALL patients who underwent initial induction therapy with alternating Hyper CVAD/MA therapy. Antibodies against 23 types of treatment resistance-associated proteins were used for immunohistochemical analysis of tumor specimens obtained from the patients, and correlations between the results of immunohistochemistry and the overall survival (OS) were retrospectively analyzed using the Kaplan-Meier method. (2) A Review of the Literature in the mechanisms underlying treatment resistance in hematopoietic malignancies. Results: (1) Case report: Based on the patterns of expression of the enzymes involved in treatment resistance, we classified the patients (Urayasu classification for ALL, which we believe would be very useful for accurately stratifying patients with ALL according to the predicted prognosis), as follows: Good prognosis group; n =1, 5%: AKR1B1(+)/AKR1B10(-), 5-year overall survival (OS), 100%; Intermediate prognosis -1 group; n= 9, 5%: AKR1B1(-)/AKR1B10(-) plus MRP1(-), 5-year OS, 68%; Intermediate-2 prognosis group; n = 6.3%: AKR1B1(-)/AKR1B10(-) plus MRP1(+), median survival, 17 months, 5-year OS, 20%; Poor prognosis group; n = 3, 16%: AKR1B1(-)/AKR1B10(+), median survival, 18 months, 5-year OS, 0%. n=2. (2) Review of Literature: A total of 27 types (32 subtypes) of anti-hematologic malignancy drugs were classified into nine categories based on the combined effects on the drugs of the four major drug-metabolic pathways present within the hematologic malignant cells. Conclusions: (1) Case report: The Urayasu classification for ALL is considered as being reliable for predicting the prognosis of patients with ALL after the initial Hyper CVAD/MA remission induction therapy. (2) Review of Literature: A total of 27 anti-hematologic malignancy agents were classified into nine categories based on the combined effects on the drugs of the four major intracellular metabolic pathways found within the hematologic malignant cells.

Abstract:

Background: The three-dimensional (3D) culture system that uses polymer particles with a bone marrow stroma cell feeder layer reproduces a biostructural hematopoiesis state effectively as compared to the conventional two-dimensional (2D) culture method. The 3D culture that maintains normal hematopoiesis, including prolongation of the hematopoietic stem cell proliferation and differentiation. The bone marrow stromal cells in a 3D culture, alter leukemic cell growth and protect the leukemic cells from anticancer agents. However, the mechanism of stromal cells on the hematopoietic stem cell proliferation and differentiation and neoplastic cells, including leukemia in the 3D culture, still bear many questions. Methods: We assessed the mechanism of two different bone marrow-derived stromal cells (i.e., MS-5 and Tst-4) bearing different characteristics, by using for a feeder layer in the 3D culture to compare the supportive action to leukemic cells. We focused on the role of the 3D culture constructed with the bone marrow stromal cells on the leukemic cell growth. Multiple myeloma cells are strongly related to the stromal cells in their proliferation; hence, the cloned MM1.S cells derived from multiple myeloma were cocultured in the 3D, and their cell growth was examined. We also examined the effect of the antineoplastic agent, bortezomib, which is a proteasome inhibitor, in the 3D culture system with a different stromal cell feeder. Results and conclusions: When MM1.S myeloma cells were cultured with MS-5 stroma in a 3D condition, the cell growth was found to be slow compared with that in the 2D culture and also with those in both the 2D and 3D cocultures with Tst-4 stroma. The MS-5 cells in the 3D culture protected the MM1.S cells from the cytocidal effect of the bortezomib treatment. Different kinetics of the MM1.S cells were observed depending on the stromal cells, suggesting their inherent and complicated characteristic.

Abstract: The ADRENALINE pilot study explores the role of physical activity in health outcomes among patients with Chronic Lymphocytic Leukemia (CLL), focusing on disease markers, functional capacity, immune parameters, and quality of life. This baseline analysis includes treatment-naive participants enrolled between September 2023 and August 2024, prior to randomization. Eleven patients (aged 47–78 years) underwent assessments of body composition, cardiovascular fitness, muscular strength, and immune profiling. Quality of life was evaluated using validated questionnaires (FACIT-F, EORTC QLQ-30/CLL17), and daily activity was objectively measured via accelerometry. Correlation analyses examined associations between physical activity, muscle strength, lean mass, and physical aptitude. Despite high self-reported physical function, participants demonstrated suboptimal body composition and cardiovascular fitness. Accelerometry revealed marked sedentary behavior, particularly among females, and overall activity levels were below current recommendations. Moderate-to-vigorous physical activity correlated positively with muscular strength and lean mass. Immune profiling identified variability in key markers, warranting further investigation of their relationship with physical activity. These findings highlight the need for tailored interventions to increase activity and reduce sedentary time in CLL patients and support incorporating functional and immune monitoring into survivorship care.

Abstract: Background: Hereditary Multiple Exostoses (HME) is a rare autosomal dominant skel-etal disorder resulting from loss-of-function variants in the EXT1, EXT2, or EXT3 genes. While malignant transformation into chondrosarcoma is well documented, the inci-dence and characterization of non-skeletal malignancies in HME remain poorly de-fined. Objective: To comprehensively review the literature for reported cases of non-skeletal malignancies in individuals with HME and evaluate a potential association with he-matologic cancers, particularly in the pediatric population. Methods: A thorough literature search was conducted in the PubMed database up to May 2025 using search terms related to HME and malignancy. Eligible reports includ-ed case descriptions of non-skeletal cancers occurring in patients with confirmed or suspected HME. Extracted data included patient age, sex, cancer type, and available genetic or molecular findings. Results: Thirteen cases of non-skeletal malignancies associated with HME were identi-fied. Fewer than half underwent molecular genetic testing. Six cases occurred in pedi-atric patients, four of which involved hematologic malignancies—three leukemias and one Burkitt lymphoma. In adults, malignancies affected a range of organ systems, in-cluding respiratory, gastrointestinal, nervous, and endocrine. A marked male pre-dominance was observed (11 males vs. 2 females). Conclusions: Although a definitive causal relationship cannot be established, hemato-logic malignancies in pediatric HME patients appear to be disproportionately repre-sented among reported cases. This finding highlights the need for further investigation through large-scale, population-based studies incorporating both clinical and genetic data.

Abstract: Syphilis is a chronic infectious disease caused by Treponema pallidum which stands as one of the most significant imitators in clinical medicine. Its wide variety of manifestations can mimic autoimmune, inflammatory, and neoplastic disorders. Hereby we present a case of a 27-year-old male initially suspected of cutaneous T-cell lymphoma (CTCL) based on lymphadenopathy, systemic weight loss, ulcerative cutaneous lesions, and fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET-CT) findings of hypermetabolic nodes above and below the diaphragm. Histopathological analysis suggested pleomorphic lymphoid proliferation, while imaging supported the suspicion of malignancy. However, subsequent biopsies revealed plasmacytic and lymphocytic infiltration without clonality, and treponemal serologies confirmed secondary syphilis. The patient was referred for anti-treponemal therapy resulting in the resolution of the initial symptoms. This case highlights how syphilis can closely imitate hematologic malignancy, particularly CTCL, at both clinical and histopathological levels. We also review published reports of syphilis masquerading as malignancies and propose a structured diagnostic algorithm. We believe that the early inclusion of syphilis in differential diagnosis is critical to avoid misdiagnosis and appropriate treatment delays.

Abstract: Pulmonary hypertension (PH) causes morbidity and mortality in sickle cell disease (SCD). The release of heme during hemolysis triggers endothelial dysfunction and contributes to PH. Long non-coding RNAs (lncRNAs) may play a pivotal role in endo-thelial dysfunction and PH pathogenesis. This study assessed the regulatory role of the lncRNA heme oxygenase-1 (HMOX1) axis in SCD-PH pathogenesis. Total RNAs were isolated from 15-17 weeks sickle cell (SS) mice and littermate controls (AA) lungs and subjected to lncRNA expression profiling using the Arrystar™ lncRNA array. Raw signal intensities were normalized in quantile method by GeneSpring GX software. Volcano plot filtering was used to screen for differentially expressed (DE) lncRNAs and mRNAs with statistical significance (fold change >1.5, p< 0.05). A total of 2,302 lncRNAs were upregulated and a total of 2,546 lncRNAs were downregulated in lungs of SS mice compared to AA mice. To validate DE of lncRNAs and mRNAs, 6 lncRNAs and 6 mRNAs were selected for quantitative PCR. Metastasis-associated lung adenocarcino-ma transcript 1 (MALAT1) and HMOX1 levels were found to be increased in SS samples. Human pulmonary artery endothelial cells (HPAECs) were treated with hemin and analyzed for MALAT1 or HMOX1 levels, which were increased in hemin-treated HPAECs. Lastly, loss of MALAT1 function reduced HMOX1 levels and increased markers of endothelial dysfunction (ET-1 and VCAM1). These results suggest that SCD modulates the MALAT1-HMOX1 axis and further characterization of MALAT1 function may provide new insights into SCD-associated endothelial dysfunction, PH pathogen-esis, and identify novel therapeutic targets.