RUNX1 alterations contribute to pediatric myeloid malignancies through both germline predisposition syndromes and somatic leukemogenic events, but their clinical and biological significance in children remains incompletely defined. This retrospective single-center study evaluated six pediatric patients with myelodysplastic syndromes or acute leukemias harboring RUNX1 variants, integrating clinical, cytogenetic, and targeted next-generation sequencing data, with germline status confirmed using...
The liver is central to drug metabolism and a critical site of disease progression, making vascularized in vitro liver models essential for disease modeling, drug discovery, and mechanistic research. However, recapitulating dynamic in vivo drug responses while maintaining clinical relevance remains a major challenge for bioartificial liver systems. In acute myeloid leukemia (AML), patients frequently develop leukemic liver infiltration and chemotherapy-induced hepatotoxicity, both of which...
Pediatric acute myeloid leukemia (pedAML) is a childhood malignancy with relapse rates of approximately 30%. CD68, a macrophage marker involved in phagocytosis and macrophage recruitment, may contribute to AML biology. We analyzed CD68 expression using the TARGET database and performed survival analyses, mRNA/protein profiling, and functional assays in AML cell lines, pedAML samples, and cord blood samples. High CD68 transcript levels correlated with KMT2A-rearrangements and inversion 16....
Next-generation sequencing (NGS) clonality assessment has the potential to overcome the conventional limitations of PCR-based methods. This study aimed at comparing the performance and concordance of the EuroClonality-NGS approach and the LymphoTrack^(®) Dx assay for immunoglobulin (IG)/T-cell receptor (TR)-marker identification at diagnosis. Across four quality-control rounds, six Italian laboratories analyzed 23 acute lymphoblastic leukemia (ALL) and five chronic lymphocytic leukemia (CLL)...
CONCLUSION: Cypripedin induces apoptosis in Jurkat T-ALL cells, synergizes with BTZ, and modulates ER stress through GRP78 ubiquitination. These findings support its further development as a potential T-ALL therapeutic.
CONCLUSION: This study expands the spectrum of RUNX1 fusions and highlights the integral diagnostic value of morphology, flow cytometry, cytogenetics, FISH, and NGS analyses for broad structural variant detection in clinical practice. Furthermore, the truncating mutation in one allele of RUNX1 and RUNX1::ARID1B of the second allele detected with advanced disease suggests the possibility of combined transcriptional and chromatin regulatory alterations in disease recurrence in the patient.
To assess factors associated with methotrexate-induced oral mucositis and its impact on the quality of life of pediatric patients with acute lymphoblastic leukemia, considering chemotherapy dose and mucositis severity within a clinical context where photobiomodulation is routinely used as part of the institutional care protocol. A cross-sectional study was conducted with 113 pediatric patients aged 5 to 18 years undergoing methotrexate-based chemotherapy between 2020 and 2024 in a university...
Due to the heterogeneity in cancer patients, accurate prediction of cancer drug response is key to achieving personalized medicine. The biological differences between cell lines and tumor tissues, as well as the domain shift caused by diverse drug mechanisms of action, make it difficult for existing methods to effectively capture the complex relationships between multimodal features. In this study, we propose a multimodal feature fusion and feature disentanglement model, named MDCDR. The model...
Loss-of-function mutations in BCOR, a subunit of the non-canonical Polycomb Repressive Complex 1.1 (PRC1.1), are frequently observed in acute myeloid leukemia (AML) and associate with adverse risk. Paradoxically, leukemic stem cell viability in BCOR wild-type AMLs strongly depends on PRC1.1 activity. Here, we use BCOR and KDM2B degron models to study PRC1.1 dependency in leukemic cells and find that BCOR is a bridging factor tethering the catalytic and chromatin-binding moieties of the PRC1.1...
Acute lymphoblastic leukaemia (ALL) results from the uncontrolled growth of lymphoid progenitors, yet the immunogenetic factors behind this remain poorly understood. A connection between specific HLA alleles, multi-locus haplotypes and ALL predisposition was suggested, with an ethnic component to this association. This retrospective case-control study analysed 137 ALL cases and 350 ethnically-matched controls using six-digit NGS typing of HLA-A, -B, -C, -DRB1, -DQA1, -DQB1 and -DPB1 loci. Allele...
We developed machine-learning models to predict isocitrate dehydrogenase (IDH) mutation status in acute myeloid leukemia (AML) from gene expression profiles and to reconstruct missing IDH annotations across public datasets. Transcriptomic data from 19 cohorts (5844 samples) were harmonized using batch correction, and 1546 samples with known IDH status were used to train a feed-forward neural network and a logistic regression (LR) classifier within a nested cross-validation framework, followed by...
CONCLUSIONS: IL37 and C17orf99 genes showed downregulated expression, while IL1F10 gene showed upregulated expression in B-ALL. Dysregulated expression of these genes was associated with B-ALL and may be of significance in disease identification. However, further research is warranted to understand these molecular vulnerabilities in B-ALL.
CONCLUSION: This first ARIA-informed cost analysis demonstrates how resource-driven clinical decisions shape cost with conventional treatment representing a fraction of regimens incorporating novel therapies. The proposed methodology provides a scalable blueprint for future costing across settings and cancer types to support adaptive Health Technology Assessment and guide investments toward equitable childhood cancer care.
CONCLUSION: Our study defines the HMGB2-TRIM65-NLRP3 axis as a pivotal immunosuppressive pathway in DLBCL. Targeting this axis represents a promising combinatory strategy to reprogram the tumor microenvironment and overcome therapy resistance.
Advances in pediatric and adolescent young adult Hodgkin lymphoma (HL), including the incorporation of targeted therapy and immunotherapy have resulted in excellent cure rates with survival greater than 90%, including patients with advanced stage disease. Current trials seek to maintain excellent survival while reducing acute and long-term toxicities. Despite these successes, vulnerable patient populations, including Black, Hispanic, and adolescent young adult patients, continue to have inferior...
CONCLUSION: Our study suggests that NFS1 and GSDMD may serve as early diagnostic and prognostic markers in AML, offering potential targets for improved therapeutic strategies.
Elevated peripheral myeloid-derived suppressor cells (MDSCs) predicted suppressed anti-tumour immunity and poor prognosis in diffuse large B-cell lymphoma (DLBCL) patients. Here we demonstrated that tumour-derived extracellular vesicles (EVs) served as a messenger, delivering cholesterol from lymphoma cells to macrophages. Through internalisation of tumour-derived EVs, macrophages were activated and secreted IL-1β via the NLRP3/IL-1β axis, leading to IL-1β-mediated MDSC expansion, as well as T...
Mantle cell lymphoma (MCL) rarely causes glomerular disease. While immune complex-mediated and infiltrative lesions predominate, podocytopathies are exceptionally rare. We report a case of reversible focal segmental glomerulosclerosis (FSGS) occurring in the setting of blastoid-variant MCL, highlighting the paraneoplastic nature of the podocyte injury. A 69-year-old man presented with nephrotic syndrome and dialysis-dependent acute kidney injury (AKI). Kidney biopsy revealed FSGS. Subsequent...
CONCLUSIONS: We developed and validated the first nomogram for predicting DS in pediatric NHR-APL. This tool enables early risk stratification and may guide clinical decision-making to reduce early mortality.
CONCLUSIONS: Although morphology and immunohistochemistry are usually sufficient to separate CHL from NLPHL, determining light chain restriction by K/L dual ISH could provide a valuable adjunct in challenging cases, potentially improving diagnostic accuracy and patient outcomes.
CONCLUSION: Ibrutinib-venetoclax is unlikely to be cost-effective versus ibrutinib-placebo for R/R MCL in both China and the US.
Leukemia, the most common malignancy in childhood, affects individuals from prepubertal girl to women of reproductive age. It originates from immature hematopoietic cells in the bone marrow and disseminates systemically via the blood and lymphatic circulations. Although survival rates have improved substantially, standard treatments, including intensive chemotherapy and hematopoietic stem cell transplantation, often combined with total body irradiation, are highly gonadotoxic. Consequently, a...
患者男，66岁。2024年5月因“无明显诱因出现上腹部疼痛”就诊，影像学提示盆腔见卵圆形软组织密度影，考虑良性肿瘤可能性大。患者行肿物切除术。病理示肿瘤呈囊性，囊壁纤维化明显，局灶钙化，有少量长梭形细胞；囊壁部分区域见带状炎性细胞浸润，囊壁内附着纤维素样物，在纤维素样物与囊壁交界处以及纤维素样物中，见多处成簇的大细胞，呈免疫母细胞形态。免疫组织化学示梭形细胞S-100蛋白、SOX10阳性，成簇的大细胞CD20、MUM1、PAX5、CD30阳性，原位杂交示大细胞EB病毒编码的RNA（EBER）约50%阳性。诊断为神经鞘瘤囊性变伴发纤维蛋白相关大B细胞淋巴瘤。.
Although covalent and non-covalent Bruton tyrosine kinase inhibitors (BTKi) have extended clinical benefit to relapsed/refractory (R/R) and BTKi-resistant chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), there remains an unmet need for additional B-cell receptor (BCR) pathway targeted therapies for highly refractory disease. This summary highlighted latest updates from the American Society of Hematology 2025 Annual Meeting on emerging BTK-directed agents in CLL/SLL, including...
Chronic lymphocytic leukemia (CLL) is a clinically and molecularly heterogeneous disease. PKMYT1, a G2/M cell cycle kinase, has been implicated in tumor progression in several cancers, but its role in CLL remains unclear. We evaluated PKMYT1 expression in primary CLL samples and analyzed associations with cytogenetic features and clinical parameters. PKMYT1 expression was heterogeneous and correlated with adverse features, including complex karyotype and elevated leukocyte counts. Comparative...
In acute myeloid leukemia (AML), gaining chromosome 8 as the sole abnormality (sole +8) is rare. The prognostic impact and mutation profile of sole +8 AML remain unclear. We retrospectively analyzed a cohort of 75 patients with sole +8 AMLs who were diagnosed and treated at our institution. The genes most frequently harboring mutations in sole +8 AML were ASXL1 (47%), RUNX1 (32%), SRSF2 (32%), TET2 (27%), DNM3A (24%), IDH2 (24%) NRAS (23%), FLT3 (23%), and STAG2 (23%). Age-related differences in...
Chimeric antigen receptor (CAR)-T cells have demonstrated remarkable efficacy in several hematologic malignancies; however, their application in myeloid malignancies such as acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) remains limited, with no FDA-approved products to date. This limited progress largely reflects both efficacy challenges and safety concerns. CAR-T cells demonstrate poor trafficking and persistence within the bone marrow, limited activity against leukemia stem...
Multiantigen targeting chimeric antigen receptor (CAR) T cells have emerged as a strategy to mitigate antigen escape observed after single antigen targeting therapy. Our initial experience with a bivalent CD19.22.BBζ CAR T-cell construct in children, adolescents and young adults (CAYA) with B-cell acute lymphoblastic leukemia (B-ALL) demonstrated limitations in CD22 recognition, but a tolerable safety profile and efficacy prompted further evaluation. This trial enrolled patients between the ages...
CONCLUSIONS: TP53-D is common in systemic ALK-negative ALCL and is associated with leukemic disease and p53 overexpression. TP53-D did not directly affect survival, but it negated the favorable impact of low IPI and DUSP22-R on PFS, suggesting its potential value as an adverse prognostic marker.
CONCLUSION: In real-world practice, venetoclax plus obinutuzumab was associated with longer TTNT and improved OS compared to acalabrutinib as first-line therapy in patients with TP53 wild-type CLL.
The tumor microenvironment (TME) in hematologic malignancies constitutes a dynamic ecosystem supporting leukemogenesis, therapeutic resistance, and immune evasion. Key drivers of this immunosuppressive network are regulatory T cells (Tregs), a CD4+ subset conventionally defined by FoxP3 and CD25 expression. While physiological Tregs are essential for self-tolerance, leukemic blasts frequently co-opt these cells to dampen anti-tumor immunity. Here, we review the distinct roles of Tregs across the...
CONCLUSIONS: Lymphoma patients showed significantly weaker Spike-specific clonal responses and reduced diversity compared with healthy controls, supporting the association with increased patient vulnerability.
Bovine leukemia virus (BLV), an oncogenic deltaretrovirus, establishes lifelong infection in cattle and induces enzootic bovine leukosis in a subset of animals following prolonged latency. Despite extensive evidence of immune dysregulation, stage-specific transcriptional reprogramming of B cells, the primary viral reservoir remains incompletely understood. In this study, we performed a targeted RNA-sequencing analysis to characterize B-cell-associated transcriptional profiles across three...
CONCLUSION: Our findings support the presence of a CD3⁺ B cell subset with T cell-like features that is associated with tumor microenvironment remodeling and adverse clinical outcomes, highlighting molecular determinants like FLI1 and the TGF-β axis as potential therapeutic targets.
T-cell large granular lymphocyte leukaemia (T-LGLL) is a chronic lymphoproliferative disorder often associated with pure red cell aplasia (PRCA). We report a unique case of a woman in her 50s presenting with PRCA secondary to T-LGLL, in which targeted next-generation sequencing identified a somatic STAT3 P715L mutation. This variant, previously described only in germline mutation in STAT3 gain-of-function syndrome, has not been reported as a somatic mutation in T-LGLL. Immunohistochemical...
Allogeneic hematopoetic stem cell transplantation (allo SCT) is a treatment option with a unique chance of cure for patients with high-risk AML or MDS. However, the optimal path for an individual patient on its way to allo SCT is far from clear and subject of ongoing debates. Upfront transplantation "as soon as possible" competes with strategies to achieve deep remission or at least stabilization of the disease. In this context, we performed a survey among German transplant centers to assess...
CONCLUSION: In summary, the MPRG-based signature provides independent prognostic value in AML and reflects its association with an immunosuppressive microenvironment. These findings provide additional evidence that mitochondrial pathway-related genes are associated with AML prognosis and immune microenvironment features. UCP2 may represent a biologically relevant candidate gene in AML, although further mechanistic and clinical validation is required.
We hypothesized that a time-limited frontline treatment strategy with abbreviated chemoimmunotherapy followed by targeted consolidation could achieve durable disease control with manageable toxicity in CLL. We evaluated the safety and efficacy of short-course bendamustine/rituximab (BR) induction followed by venetoclax/rituximab (VR) consolidation. In a multicenter, single-arm Phase 2 trial (NCT03609593), previously untreated CLL/SLL needing therapy received BR for three 28-day cycles followed...
CONCLUSION: Substantial disparities exist in access to advanced therapies for pediatric B-ALL across Europe. Although CAR-T CD19 therapy is available in most countries, gaps in clinical trials, collaborations, and referral systems limit equitable access. Efforts to improve infrastructure and establish referral networks are essential to enhance care for patients with pediatric B-ALL.
BACKGROUND: Primary CNS lymphoma is typically diagnosed by brain biopsy, a procedure with risks and diagnostic delay. Emerging cerebrospinal fluid (CSF) biomarkers, including the myeloid differentiation primary response 88 (MYD88) L265P mutation in CSF and several chemokines, might improve diagnostic accuracy, but evidence mostly comes from retrospective, non-consecutive cohorts. We aimed to validate the diagnostic utility of CSF biomarkers in patients with suspected primary CNS lymphoma.
CONCLUSION: This is the largest epidemiological study reported on childhood AL in an AD population and in the Caribbean/Latin America zone. Survival rates in our AD population were similar to those described in European and North American studies and much better than in the Caribbean and Latin American zone.
Risk factors for relapse and non-relapse mortality (NRM) in the first years after allogeneic hematopoietic stem cells transplant (allo-HSCT) for acute myeloid leukemia (AML) are well known, but their correlation with long-term survivorship is unclear. This study aims to evaluate factors that impact on long-term survival after allo-HSCT in AML. We retrospectively analyzed data of 456 consecutive patients who received a first allo-HSCT in our center, regardless of conditioning intensity, GvHD...
Leukemia stem cells exploit cell-intrinsic ketogenesis to suppress ferroptosis and sustain disease propagation. In this issue, Han et al.¹ uncover a β-hydroxybutyrate-epigenetic-lipid remodeling axis that protects stemness by restraining ferroptosis, revealing a metabolic vulnerability with therapeutic potential.
Translational control is essential for immune function, but its roles in immune tolerance and lymphomagenesis remain poorly defined. Here, we show that Cγ1Cre-mediated deletion of Eif3e, which encodes a subunit of the eIF3 translation initiation complex, in B cells causes lymphoproliferation, malignant transformation of Eif3e-sufficient bystander lymphocytes, and premature death. Eif3e-deficient B cells upregulate the costimulatory molecule CD80, promoting CD4+ T cell activation and...
Chimeric antigen receptor T-cell (CAR-T) therapy has transformed the management of selected hematologic malignancies, particularly relapsed or refractory large B-cell lymphoma, B-cell acute lymphoblastic leukemia, and multiple myeloma. However, currently approved CAR-T strategies largely rely on lineage-associated or differentiation antigens, such as CD19 or BCMA, and therefore do not selectively distinguish malignant B cells from their normal counterparts. This limitation contributes to...
CONCLUSION: This case establishes the shared clonal origin between AITL and BL arising in the setting of CH and provides additional biological insight into the development of B-cell lymphoma associated with AITL.
Kikuchi-Fujimoto disease (KFD) is a rare, self-limiting form of necrotizing lymphadenitis that primarily affects young adults and often mimics lymphoma or autoimmune lymphadenitis both clinically and histologically. We report the case of a 28-year-old Caucasian woman with a history of Hashimoto's thyroiditis presenting with progressive cervical lymphadenopathy, fever, weight loss, and myalgia. Laboratory findings showed leukopenia, elevated transaminases, and increased LDH. Imaging revealed...
CONCLUSIONS: Among patients with newly diagnosed AML who were ineligible for intensive chemotherapy, all-oral decitabine-cedazuridine plus venetoclax caused no drug interactions and resulted in a complete response in nearly half the patients, with myelosuppressive effects. (Funded by Taiho Oncology; ASCERTAIN-V ClinicalTrials.gov number, NCT04657081.).
Extra-nodal head and neck lymphoma encompasses diverse histological subtypes and imaging appearances. Thus, it can be challenging to discriminate lymphoma from other lesions that may have similar radiological features. Herein, various lymphoma mimics will be reviewed in different anatomical locations in the head and neck including Waldeyer's ring, sinonasal tract, orbits, and salivary and thyroid glands, with reference to their clinical presentation, predisposing factors, and laboratory markers....
CONCLUSIONS: PRKCA and ABCB1 dual-enriched exosomes are key drivers of drug resistance in CML patients, and exosomal PRKCA and ABCB1 may serve as diagnostic and therapeutic targets for CML.
- Check what you can access with your account
![qrcode.14118297[1]](http://www.library.wmuh.nhs.uk/wp/wp-content/uploads/2013/06/qrcode.141182971.png)