bims-hemali Biomed News
on Hematologic malignancies
Issue of 2025–12–21
twenty-one papers selected by
Alexandros Alexandropoulos, Γενικό Νοσοκομείο Αθηνών Λαϊκό
  1. Asciminib Demonstrates Superior Efficacy and Safety in Newly Diagnosed Chronic Myeloid Leukemia in the ASC4FIRST Trial.
  2. Premaintenance PET in patients with myeloma.
  3. Innate CD8 T-cells as a potential predictive biomarker for deep molecular response in chronic myeloid leukemia patients.
  4. The role of the bone marrow microenvironment in leukemic stem cell resistance: Pathways of persistence and selection.
  5. Breaking the silence: restoring CEBPA to fight leukemia.
  6. Molecular modeling of Waldenström macroglobulinemia.
  7. Outnumbered: T-cell dominance breaks BCMA-TCE resistance.
  8. Exhaustion is getting complicated.
  9. More than an emotional support PET.
  10. Venetoclax and Homoharringtonine-Based Therapy Exhibited a Striking Response in Refractory/Relapsed Early T-Cell Precursor Acute Lymphoblastic Leukemia.
  11. No BCMA? No Problem: A CD70-Targeting CAR-NK Cell Shows Promise in High-risk Myeloma.
  12. Safety and efficacy of venetoclax-azacitidine combined with low-dose Idarubicin and cytarabine regimens for the treatment of newly diagnosed acute myeloid leukemia patients compared to the standard chemotherapy: a propensity score-matched real-world single-center experience.
  13. Plasma Cell Leukemia: Genomic Features and Their Potential Relevance for Exploring Clinical Actionability.
  14. The role of CD38 in monocytes during fibrotic progression of myeloproliferative neoplasms.
  15. Durable post-transplant survival after first-line tagraxofusp for blastic plasmacytoid dendritic cell neoplasm.
  16. Pharmacological Inhibition of miR-126 Enhances Venetoclax Activity in Acute Myeloid Leukemia.
  17. Rare CD138 negative plasma cell leukemia with pleomorphic morphology-CD319 to the rescue when traditional markers fail.
  18. Impact of Achieving Progression-Free Survival 24 on Subsequent Overall Survival in Diffuse Large B-Cell Lymphoma Patients.
  19. Successful combined treatment for primary central nervous system lymphoma with massive hemorrhage: Illustrative case.
  20. Unveiling the metal-driven death: ferroptosis and cuproptosis in leukemia.
  21. Current treatments, practical management, and emerging investigational therapies for myelofibrosis.
  1. Blood. 2025 Dec 15. pii: blood.2025029210. [Epub ahead of print]
    Asciminib Demonstrates Superior Efficacy and Safety in Newly Diagnosed Chronic Myeloid Leukemia in the ASC4FIRST Trial.
    Jorge E Cortes, Timothy P Hughes, Jianxiang Wang, Dong-Wook Kim, Dennis Dong Hwan Kim, Jiri Mayer, Yoew-Tee Goh, Philipp le Coutre, Gabriel Etienne, Inho Kim, David Andorsky, Felice Bombaci, Ghayas C Issa, Naoto Takahashi, Shruti Kapoor, Rajendra Jinwal, Kamel Malek, Tracey McCulloch, Lillian Yau, Richard A Larson, Andreas Hochhaus.
      Many patients receiving frontline tyrosine kinase inhibitors (TKIs) for chronic phase chronic myeloid leukemia (CML-CP) experience inadequate disease control and/or adverse events (AEs) that impair quality of life. Treatments offering optimal efficacy, safety, and tolerability will support long-term therapy. In the primary analysis from ASC4FIRST, a phase 3 randomized trial comparing asciminib with investigator-selected TKIs (IS-TKIs) in newly diagnosed CML-CP, asciminib demonstrated superior efficacy vs all IS-TKIs and vs imatinib in the imatinib stratum, meeting both primary objectives. In the secondary analysis (2.2 years median follow-up), major molecular response (MMR) rate at week 96 was 74.1% with asciminib vs 52.0% with IS-TKIs (treatment difference, 22.4%; 95% CI, 13.6%-31.3%; 1-sided P<.001), and 76.2% with asciminib vs 47.1% with imatinib in the imatinib stratum (treatment difference, 29.7%; 95% CI, 17.6%-41.8%; 1-sided P<.001), meeting both key secondary objectives. MMR rate was 72.0% with asciminib vs 56.9% with second-generation (2G) TKIs (treatment difference, 15.1%; 95% CI, 2.3%-28.0%; 1-sided P<.05), suggesting possible clinical benefit although the study was not designed to formally confirm statistical significance for this secondary endpoint. Safety/tolerability remained favorable with asciminib vs IS-TKIs. Dose reductions and interruptions, respectively, occurred with asciminib (18.5% and 46.5%), imatinib (23.2% and 47.5%), and 2G TKIs (54.9% and 63.7%). The hazard ratio for time to discontinuation of treatment due to AEs for asciminib vs 2G TKIs was 0.46 (95% CI, 0.215%-0.997%). With longer follow-up, asciminib continued to demonstrate a favorable benefit-risk profile over IS-TKIs and imatinib, supporting its potential as a treatment option for newly diagnosed CML-CP.
    DOI:  https://doi.org/10.1182/blood.2025029210
  2. Blood. 2025 Dec 18. 146(25): 3130
    Premaintenance PET in patients with myeloma.
      
    DOI:  https://doi.org/10.1182/blood.2025032271
  3. Cancer Immunol Immunother. 2025 Dec 19. 75(1): 16
    Innate CD8 T-cells as a potential predictive biomarker for deep molecular response in chronic myeloid leukemia patients.
    Emilie Cayssials, Lucie Lefèvre, Amandine Decroos, Florence Jacomet, Nathalie Piccirilli, Florence Tartarin, François Guilhot, Jean-Claude Chomel, Philippe Rousselot, Franck E Nicolini, Stéphanie Ragot, Jean-Marc Gombert, Lydia Roy, André Herbelin, Alice Barbarin.
      In chronic myeloid leukemia (CML), the role of immune effectors has been suggested in the achievement of a sustained deep molecular response (DMR) and treatment-free remission (TFR) after tyrosine kinase inhibitor (TKI) discontinuation. A contributory role of the distinct new innate CD8 T-cell pool in control of CML residual disease after TKI cessation was recently highlighted. Here, we evaluated longitudinally whether innate CD8 T-cells predict CML therapy success in a cohort of newly diagnosed CML patients treated in the DASA-PegIFN clinical trial. After 3 months of treatment (M3), we observed a significant increase in innate CD8 T-cell frequency as compared to diagnosis, together with an early shift within the pool of CD8 T-cells toward an innate/memory phenotype. We also found that patients with high innate CD8 T-cell frequency at M3 achieved DMR earlier and at higher rates than patients with low innate CD8 T-cell frequency. Remarkably, this signature pre-existed at the time of diagnosis, suggesting the possible role of the patient's initial individual immune status. High innate CD8 T-cell frequency was also associated with maintaining DMR stability for 2 years. Taken together, our findings highlight innate CD8 T-cells as a potential marker for CML therapy success and TFR eligibility.
    Keywords:  Chronic myeloid leukemia; Deep molecular response; Immune biomarker; Innate CD8 T-cell
    DOI:  https://doi.org/10.1007/s00262-025-04256-0
  4. Crit Rev Oncol Hematol. 2025 Dec 14. pii: S1040-8428(25)00478-0. [Epub ahead of print]218 105090
    The role of the bone marrow microenvironment in leukemic stem cell resistance: Pathways of persistence and selection.
    Serena Barachini, Marina Montali, Irene Sofia Burzi, Eleonora Pardini, Gisella Sardo Infirri, Raffaella Cassano Cassano, Iacopo Petrini.
      Chronic Myeloid Leukemia is driven by the BCR::ABL1 fusion gene, which transforms bone marrow stem cells. Tyrosine kinase inhibitors have markedly improved patients' outcomes. However, only about 20 % of patients are cured, remaining free of relapses after the achievement of a profound and durable molecular remission of the disease and the suspension of tyrosine kinase inhibitors. In most cases, leukemic stem cells persist and contribute to disease relapse after treatment suspension or the development of acquired resistance to tyrosine kinase inhibitors. Emerging evidence underscores the pivotal role of the bone marrow microenvironment in sustaining leukemic stem cells and contributing to drug resistance. Stromal progenitor cells within the bone marrow niche play a key role in supporting the persistence and survival of resistant leukemic stem cells. This review examines how the bone marrow microenvironment and its components promote drug resistance through mechanisms such as metabolic reprogramming, aberrant signaling, and protective cellular interactions. These insights reveal potential therapeutic strategies aimed at disrupting the leukemic stem cell supportive niche to achieve more effective eradication of resistant clones. Understanding the complex interplay between leukemic stem cells and their microenvironment is crucial for developing targeted treatments that can overcome resistance and achieve long-term remission in patients with chronic myeloid leukemia.
    Keywords:  Bone marrow microenvironment; Chronic myeloid leukemia; Drug resistance; Leukemic stem cell; Tyrosine kinase inhibitor
    DOI:  https://doi.org/10.1016/j.critrevonc.2025.105090
  5. Blood. 2025 Dec 18. 146(25): 3014-3015
    Breaking the silence: restoring CEBPA to fight leukemia.
    Nicola K Wilson, Berthold Göttgens.
      
    DOI:  https://doi.org/10.1182/blood.2025031363
  6. Blood. 2025 Dec 18. 146(25): 3012-3013
    Molecular modeling of Waldenström macroglobulinemia.
    Gareth J Morgan, Faith E Davies.
      
    DOI:  https://doi.org/10.1182/blood.2025031066
  7. Blood. 2025 Dec 18. 146(25): 3010-3011
    Outnumbered: T-cell dominance breaks BCMA-TCE resistance.
    Paola Neri.
      
    DOI:  https://doi.org/10.1182/blood.2025031063
  8. Blood. 2025 Dec 18. 146(25): 3008-3010
    Exhaustion is getting complicated.
    William J Murphy.
      
    DOI:  https://doi.org/10.1182/blood.2025031002
  9. Blood. 2025 Dec 18. 146(25): 3006-3008
    More than an emotional support PET.
    Jens Hillengass.
      
    DOI:  https://doi.org/10.1182/blood.2025031179
  10. MedComm (2020). 2025 Dec;6(12): e70549
    Venetoclax and Homoharringtonine-Based Therapy Exhibited a Striking Response in Refractory/Relapsed Early T-Cell Precursor Acute Lymphoblastic Leukemia.
    Xiang Zhang, Hongsheng Zhou, Liping Mao, Yinjun Lou, Lijing Shen, Ying Lu, Zhenfang Liu, Xiuzhen Tong, Aiping Zhang, Tingbo Liu, Na Zhang, Xingnong Ye, Juying Wei, Meihong Luo, Shaoyuan Wang, Qingxian Bai, Jian Hou, Qifa Liu, Hongyan Tong, Jie Jin, Wenjuan Yu.
      Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is an aggressive subtype of T-ALL. Once refractory or relapsed, it is associated with a poor prognosis, with a complete remission (CR) rate of 36%-46% following re-induction therapy. Previously, we reported a synergistic effect of venetoclax (VEN) and homoharringtonine (HHT) in ETP-ALL, which potentially elicits notable clinical responses. Herein, we investigated the efficacy and safety of the V-HAG regimen (VEN, HHT, cytarabine, and granulocyte colony-stimulating factor [G-CSF]) in patients with refractory/relapsed ETP-ALL through a prospective, multicenter, single-arm, open-label, phase 2 clinical trial. A total of 18 patients were enrolled, and 100% of these patients achieved CR or CR with incomplete hematological recovery (CRi) after 1 cycle of the V-HAG regimen as re-induction therapy. As a follow-up, both the relapse rate and mortality rate were 33.3%. The 1-year overall survival and relapse-free survival were 76.7% (95% confidence interval [CI]: 53.2%-100.0%) and 55.7% (95% CI: 28.8%-82.6%), respectively. The most common grade 3-4 adverse events were neutropenia (100%), anemia (88.9%), and thrombocytopenia (100%). Notably, the VEN- and HHT-based therapy, V-HAG regimen, exhibits an extremely high efficacy in the treatment of patients with refractory/relapsed ETP-ALL with good tolerance, and it provides a promising therapeutic strategy for improving their outcomes.
    Keywords:  early T‐cell precursor acute lymphoblastic leukemia; homoharringtonine; refractoriness; relapse; venetoclax
    DOI:  https://doi.org/10.1002/mco2.70549
  11. Blood Cancer Discov. 2025 Dec 19. OF1-OF2
    No BCMA? No Problem: A CD70-Targeting CAR-NK Cell Shows Promise in High-risk Myeloma.
    Don M Benson, Michael A Caligiuri.
      Despite recent advances, multiple myeloma remains essentially incurable for most patients, particularly those with high-risk cytogenetics and those whose disease relapses after BCMA-targeting therapies. A novel CD27 CAR_sIL15 NK cell targeting CD70 may offer new hope in this area of urgent, unmet medical need. See related article by Lin et al., p. XX .
    DOI:  https://doi.org/10.1158/2643-3230.BCD-25-0394
  12. Ann Hematol. 2025 Dec 18.
    Safety and efficacy of venetoclax-azacitidine combined with low-dose Idarubicin and cytarabine regimens for the treatment of newly diagnosed acute myeloid leukemia patients compared to the standard chemotherapy: a propensity score-matched real-world single-center experience.
    Xiao-Tong Chen, Qi Li, Yan-Qiu Zhao, Sheng-Jin Fan.
      
    Keywords:  Acute myeloid leukemia; Azacitidine; Cytarabine; Idarubicin; Induction therapy; Measurable residual disease; Response rate; Survival; Venetoclax
    DOI:  https://doi.org/10.1007/s00277-025-06653-y
  13. Blood Adv. 2025 Dec 18. pii: bloodadvances.2025018342. [Epub ahead of print]
    Plasma Cell Leukemia: Genomic Features and Their Potential Relevance for Exploring Clinical Actionability.
    Meera Mohan, Natalie Danziger, Othman Salim Akhtar, Ravi Narra, Marcelo C Pasquini, Sabarinath Venniyil Radhakrishnan, Binod Dhakal, Anita D'Souza, Douglas I Lin, Caleb Ho, Razelle Kurzrock.
      Plasma cell leukemia (PCL) is rare and aggressive. Plasma cells from PCL patients were interrogated by next-generation sequencing (NGS). We compared NGS in 18 PCL patients (peripheral blood, n = 10; bone marrow [BM], n = 8) and 1,742 multiple myeloma (MM) samples. Mutations of TP53, CCND1, and KRAS were commonly seen in both diseases. Alterations in DIS3 (17% vs. 1%), CCND2 (22% vs. 15%), PIK3R1 (6% vs. 0%), and MAP3K1 (6% vs. 2%) were more common in PCL compared to MM (p < 0.05). Translocations occurred in 11 (61.1%) PCL patients; IGH::CCND1 and IGH::MYC were more frequent in PCL compared to MM (22% vs. 14%, p = NS, and 11% vs. 1%, p < 0.05). Druggable aberrations in BRAF, CCND1, PIK3R1, and RAS may be targeted in biomarker-driven therapeutic clinical trials.
    DOI:  https://doi.org/10.1182/bloodadvances.2025018342
  14. Blood. 2025 Dec 17. pii: blood.2025028703. [Epub ahead of print]
    The role of CD38 in monocytes during fibrotic progression of myeloproliferative neoplasms.
    Yiru Yan, Jinqin Liu, Songyang Zhao, Fuhui Li, Lin Yang, Zefeng Xu, Tiejun Qin, Xiaofan Zhu, Wenbin An, Zhongxun Shi, Wenyi Shen, Peihong Zhang, Gang Huang, Raajit K Rampal, Zhijian Xiao, Bing Li.
      Proinflammatory signaling is a hallmark of myeloproliferative neoplasms (MPNs). Several studies have shown that monocytes are a major source of proinflammatory cytokines and monocyte-derived fibrocytes play a pivotal role in the pathogenesis of myelofibrosis (MF). To further explore the role of monocytes in MF, we generated inducible NrasG12D/+Jak2V617F/+ (NJ) mice. Recipients transplanted with NJ BM cells developed MF with an early onset of anemia and monocytosis. In vitro, NJ recipients' BM nucleated cells exhibited increased quantity of CD45+CollagenI+ fibrocytes, which were mainly derived from the Ly6chigh monocytes. RNA sequencing identified a significant elevated expression of CD38 (a nicotinamide adenine dinucleotide (NAD)+ hydrolase) in Ly6chigh monocytes from NJ mice, which results in pronounced lower level of NAD+. In humans, CD14+ monocytes from MF patients showed significantly higher expression of CD38 than controls and monocytes from polycythemia vera (PV) patients with grade 1 fibrosis had higher CD38 expression than those without fibrosis. Finally, boosting NAD+ via pharmacological CD38 targeting or NAD+ precursor supplementation inhibited the differentiation of fibrocytes in vitro and targeting CD38 can effectively prevent the onset of fibrosis in vivo. Collectively, our findings shed light on the role of CD38 in monocytes and suggest potential clinical applications such as use of CD38 as a biomarker of fibrotic progression and potential clinical utility of CD38 inhibition in patients with MF.
    DOI:  https://doi.org/10.1182/blood.2025028703
  15. Leuk Lymphoma. 2025 Dec 17. 1-5
    Durable post-transplant survival after first-line tagraxofusp for blastic plasmacytoid dendritic cell neoplasm.
    Naveen Pemmaraju, Marina Konopleva, Muzaffar Qazilbash, Anthony S Stein, David A Rizzieri, Eunice S Wang, Sumithira Vasu, Ira Gupta, Andrew A Lane.
      
    DOI:  https://doi.org/10.1080/10428194.2025.2595226
  16. Blood. 2025 Dec 15. pii: blood.2025029875. [Epub ahead of print]
    Pharmacological Inhibition of miR-126 Enhances Venetoclax Activity in Acute Myeloid Leukemia.
    Lianjun Zhang, HyunJun Kang, Melissa Valerio, Dinh Hoa Hoang, Khyatiben V Pathak, Krystine Garcia-Mansfield, Xiyuan Lu, Wancheng Guo, Yu-Hsuan Fu, Xin He, Ying-Chieh Chen, Zhenhua Chen, Lucy Y Ghoda, Ralf Buettner, Zhuo Li, Amanda Blackmon, Ling Li, Bin Zhang, Patrick Pirrotte, Guido Marcucci, Ya-Huei Kuo, Le Xuan Truong Nguyen.
      Leukemic stem cells (LSCs) in acute myeloid leukemia (AML) depend on oxidative phosphorylation (OXPHOS) sustained by fatty acid oxidation (FAO) and mitochondrial fusion (mitofusion). We demonstrate that miR-126 maintains LSC function by promoting BCL-2-dependent FAO, OXPHOS, and mitofusion, whereas its inhibition disrupts mitochondrial metabolism, induces mitochondrial fission (mitofission), and triggers apoptosis. Mechanistically, miR-126 stabilizes BCL-2 via the SPRED1/ERK axis, which upregulates CPT1B (FAO) and NRF2 (antioxidant response) while regulating mitochondrial dynamics through DRP1 phosphorylation (inhibiting mitofission) and MFN1/2 phosphorylation (enhancing mitofusion). miRisten, a CpG-conjugated anti-miR-126 oligonucleotide now in clinical trials (NCT07025564), synergized with venetoclax (VEN) to suppress FAO/OXPHOS, promote mitofission, and impair LSC homeostasis. In vivo, miRisten potentiated the VEN/azacitidine (AZA) regimen, an FDA-approved therapy for older or unfit AML patients, significantly prolonging survival in patient-derived xenograft models. VEN/miRisten combination also reduced LSC burden and restored VEN sensitivity, establishing miR-126 inhibition as a transformative therapeutic strategy in AML.
    DOI:  https://doi.org/10.1182/blood.2025029875
  17. J Hematop. 2025 Dec 20. 19(1): 1
    Rare CD138 negative plasma cell leukemia with pleomorphic morphology-CD319 to the rescue when traditional markers fail.
    Richa Chauhan, Selvan P, Jasmita Dass, Pradeep Kumar, Manoranjan Mahapatra.
       BACKGROUND: Flow cytometric identification of plasma cells can be confounded by therapeutic anti-CD38 antibodies, a phenomenon commonly encountered during measurable residual disease (MRD) assessment after chemo/immunotherapy. Less frequently, loss of plasmacell gating markers may occur due to the disease process itself. In low-resource settings, diagnostic and MRD flow cytometry panels are tailored for cost-effective use of CD markers. At baseline diagnosis, CD38, CD138, and CD45 are usually sufficient as backbone plasma-cell gating markers, and alternate markers are not routinely required.
    CASE DESCRIPTION: We present a case of plasma cell leukemia in which standard diagnostic flow cytometry panels were challenged by variable CD138 expression. Given the difficulty in identifying plasma cells using conventional markers, an expanded flow cytometry panel incorporating antibody CD319 (SLAMF7) was employed.
    RESULTS: The inclusion of CD319 enabled reliable detection of clonal plasma cells despite predominant loss of CD138 expression. This approach allowed identification of circulating malignant plasma cells outside the setting of therapeutic anti-CD38 antibody interference.
    CONCLUSION: Use of alternate plasma-cell gating markers beyond the conventional backbone can be critical even in upfront diagnostic settings. Incorporating multiple, non-overlapping plasma-cell markers-including antibodies designed to avoid therapeutic masking-improves plasma-cell detection in both MRD assessment and initial diagnostic flow cytometry panels.
    Keywords:  CD138 loss; Flow cytometry; Plasma cell leukemia; Plasma-cell gating; SLAMF7 (CD319)
    DOI:  https://doi.org/10.1007/s12308-025-00677-z
  18. Cancer Sci. 2025 Dec 19.
    Impact of Achieving Progression-Free Survival 24 on Subsequent Overall Survival in Diffuse Large B-Cell Lymphoma Patients.
    Ayumi Fujimoto, Wataru Munakata, Gakuto Ogawa, Ryunosuke Machida, Tomotaka Suzuki, Kazuyuki Shimada, Tsutomu Kobayashi, Ken Ohmachi, Tomohiro Kinoshita, Kiyoshi Ando, Dai Maruyama, Hirokazu Nagai.
      The impact of achieving progression-free survival at 24 months (PFS24) on subsequent survival in patients with diffuse large B-cell lymphoma (DLBCL) relative to the general population remains debatable. We assessed the impact of achieving PFS24 in newly diagnosed DLBCL patients using data from JCOG0601, a prospective study of DLBCL patients treated with R-CHOP. Among 409 eligible patients (median follow-up: 5.3 years), 334 (82%) achieved PFS24, whereas 66 (16%) did not. Patients who achieved PFS24 had significantly better overall survival (OS) than those who did not (median OS, not reached vs. 1.3 years; p < 0.001). Similar results were observed for PFS12 and PFS60. The OS for patients after achieving PFS24 or PFS60 was not markedly different from that of the age-, sex-, and calendar period-matched Japanese general population (PFS24: standardized mortality ratio [SMR] 1.29, 95% confidence interval [CI] 0.72-2.12, p = 0.39; PFS60: SMR 1.43, 95% CI 0.47-3.33, p = 0.55). Conversely, the OS for patients after achieving PFS12 was significantly worse than that of the general population (SMR 2.30, 95% CI 1.59-3.22, p < 0.001). The primary cause of death among patients who achieved PFS12 was DLBCL, whereas the mortality rate from DLBCL among those who achieved PFS24 or PFS60 was less than 5%. Multivariable analysis showed that having two or more extranodal involvements (OR 2.76 [95% CI 1.39-5.46], p = 0.004) was the only significant risk factor for failing to achieve PFS24. Our findings suggest that PFS24 can serve as an early endpoint of OS in patients with DLBCL.
    Keywords:  diffuse large B‐cell lymphoma; overall survival; prognosis; progression‐free survival; risk factors
    DOI:  https://doi.org/10.1111/cas.70304
  19. Surg Neurol Int. 2025 ;16 466
    Successful combined treatment for primary central nervous system lymphoma with massive hemorrhage: Illustrative case.
    Yusuke Kobayashi, Yuma Miki, Daisuke Tanioka, Yuta Sakuragi, Atsushi Terajima, Yosuke Sato, Hitomi Kera, Kouzou Murakami, Yoichi Morofuji.
       Background: Primary central nervous system lymphoma (PCNSL) is a rare tumor, accounting for only 1-2% of all primary brain tumors, with most cases being diffuse large B-cell lymphoma (DLBCL). Because these lymphomas can rapidly worsen, prompt and accurate histological diagnosis, followed by early treatment initiation, are essential for improved prognosis. Extensive surgical resection has not demonstrated a clear survival benefit, and a minimally invasive biopsy is recommended. Hemorrhage within lesions is exceedingly rare, with few reports available.
    Case Description: A 73-year-old woman presented with progressive aphasia and right-sided hemiparesis. Imaging revealed a lesion from the left basal ganglia to the frontal lobe, suggestive of glioblastoma but not ruling out PCNSL. She developed deep vein thrombosis and pulmonary embolism, requiring anticoagulation therapy. Steroid therapy for acute brain edema provided transient improvement, but a massive intratumoral hemorrhage occurred. We performed a frameless robot-guided stereotactic biopsy and craniotomy for hematoma evacuation in a single operation. Final pathology confirmed DLBCL. Subsequent high-dose methotrexate plus rituximab therapy and radiation led to marked tumor shrinkage.
    Conclusion: Combining robot-guided stereotactic biopsy with craniotomy in PCNSL with hemorrhage ensures precise diagnosis, effective decompression, and optimal treatment planning.
    Keywords:  Biopsy; Combined treatment; Hematoma evacuation; Lymphoma; Robot-guided
    DOI:  https://doi.org/10.25259/SNI_514_2025
  20. Eur J Med Res. 2025 Dec 17. 30(1): 1241
    Unveiling the metal-driven death: ferroptosis and cuproptosis in leukemia.
    Zhe Chen, Jieni Yu, Leihua Fu, Jiaping Fu, Zhijian Zhang, Pan Hong, Weiying Feng.
      Cell death is essential for tumor cells and can occur due to damage or aging. Traditional concepts such as necrosis and apoptosis do not completely account for it. New forms, such as cuproptosis and ferroptosis, involve metal ion buildup and relate to cell metabolism, signaling, and drug resistance. These forms are particularly relevant in leukemia development. This review discusses the advancements in understanding the mechanisms of ferroptosis and cuproptosis and their impact on leukemia, opportunities and challenges in leukemia treatment are explored, emphasizing the potential therapeutic direction of ferroptosis and cuproptosis, to provide new theoretical basis and strategies for the treatment of clinical leukemia diseases.
    Keywords:  Cuproptosis; Ferroptosis; Leukemia; Programmed cell death; Reactive oxygen species
    DOI:  https://doi.org/10.1186/s40001-025-03518-y
  21. Expert Rev Hematol. 2025 Dec 20. 1-20
    Current treatments, practical management, and emerging investigational therapies for myelofibrosis.
    Srinivas Tantravahi, Firas El Chaer, Prithviraj Bose.
       INTRODUCTION: Myelofibrosis is a clonal myeloproliferative neoplasm characterized by bone marrow fibrosis, extramedullary hematopoiesis, splenomegaly, progressive cytopenias, and systemic symptoms, with risk of leukemic transformation. Advances in understanding its molecular pathogenesis, particularly JAK-STAT signaling, have reshaped treatment approaches, though allogeneic transplantation remains the only potential cure.
    AREAS COVERED: We review current diagnostic frameworks, prognostic models, and treatment strategies, including approved JAK inhibitors and emerging investigational therapies. Literature was identified through PubMed searches and relevant conference proceedings, with emphasis on pivotal clinical trials, novel targeted agents, and evolving management of cytopenias and advanced disease.
    EXPERT OPINION: It is an exciting time in myelofibrosis research. Investigation into the molecular underpinnings of the disease and elucidation of many key pathways beyond JAK-STAT signaling have led to a profusion of new drug classes entering the clinic. The results of several, potentially paradigm-shifting key phase 3 trials are eagerly awaited. While JAK inhibitors remain the only approved agents, this could soon change. Equally, there is a major focus on next generation JAK inhibitors and mutant calreticulin antibodies. There is also increasing conversation around the need for novel endpoints, as the limitations of symptom assessment, in particular, become apparent and candidate biomarkers of disease modification emerge.
    Keywords:  Myelofibrosis; anemia; fedratinib; jak inhibitors; momelotinib; myeloproliferative neoplasms; pacritinib; ruxolitinib
    DOI:  https://doi.org/10.1080/17474086.2025.2604532
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