Hematology Reports最新文献

{"title":"Lung-Predominant Hyperinflammatory Syndrome in Therapy-Related Myelodysplastic Syndrome Responsive to Interleukin-1 Blockade.","authors":"Quinn Smith, Anna Arar-Cauley","doi":"10.3390/hematolrep18050068","DOIUrl":"10.3390/hematolrep18050068","url":null,"abstract":"<p><p><b>Background/Objectives:</b> In myelodysplastic neoplasms, autoinflammatory syndromes result from dysregulated innate immunity and cause severe, organ-dominant inflammation. Interleukin-1 signaling through the NLRP3 inflammasome is implicated in the pathogenesis of myelodysplastic disease and related inflammatory complications, especially in the context of RAS-pathway activation. Reports describing therapy-related myelodysplastic syndrome with pulmonary autoinflammatory syndromes are rare, and the efficacy of interleukin-1 blockade in this setting has not been previously documented. <b>Results:</b> A man in his 60s with therapy-related myelodysplastic syndrome (del 5q) following rectal chemoradiation developed a recurrent, lung-predominant autoinflammatory syndrome refractory to corticosteroids and Janus kinase inhibition. Next-generation sequencing identified gain-of-function mutations in NRAS, PTPN11, SF3B1, and ASXL1. On two separate occasions, anakinra produced rapid clinical improvement with normalization of inflammatory biomarkers and radiographic resolution; on both occasions, discontinuation of anakinra led to prompt relapse within days, with ferritin rising to above 5500 ng/mL and C-reactive protein exceeding 300 mg/L. <b>Conclusions:</b> This case demonstrates that interleukin-1-mediated inflammation can drive pulmonary complications in therapy-related myelodysplastic syndrome. Targeted cytokine blockade with anakinra produced reproducible and measurable clinical improvement when conventional therapies were insufficient. The recurrence of symptoms following anakinra withdrawal, and rapid improvement upon re-administration, underscores the functional link between interleukin-1-driven inflammation and clinical outcomes. The RAS/MAPK mutational context and the observed on-off response to anakinra further support an interleukin-1-driven mechanism that merits further investigation.</p>","PeriodicalId":12829,"journal":{"name":"Hematology Reports","volume":"18 5","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13600130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149030186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anticoagulants, Their Laboratory Monitoring, and Reversal.","authors":"Mohammad Barouqa, Marianne E Yassa, Nestor Dela Cruz, Maha Babker","doi":"10.3390/hematolrep18050067","DOIUrl":"10.3390/hematolrep18050067","url":null,"abstract":"<p><p>Anticoagulant therapy has undergone substantial evolution over the past century, progressing from early parenteral agents such as heparin to vitamin K antagonists (VKAs) and, more recently, to direct oral anticoagulants (DOACs). This review provides an overview of the major classes of anticoagulants, including unfractionated heparin (UFH), low molecular weight heparin (LMWH), fondaparinux, direct thrombin inhibitors, VKAs, and DOACs, with emphasis on their mechanisms of action, clinical applications, laboratory monitoring, and reversal strategies. While UFH remains widely used in acute settings, its unpredictable pharmacokinetics and risk of heparin induced thrombocytopenia have led to increased use of LMWH and fondaparinux. VKAs, historically the cornerstone of oral anticoagulation, are limited by variable dosing requirements and the need for routine monitoring. In contrast, DOACs have transformed anticoagulation management through predictable pharmacokinetics, fixed dosing, and improved safety profiles, and are now first line therapies for several thromboembolic conditions. The development of targeted reversal agents, including protamine, vitamin K, prothrombin complex concentrates, idarucizumab, and andexanet alfa, has significantly enhanced the safety of anticoagulant therapy in the setting of major bleeding or urgent procedures. Laboratory assessment remains critical for selecting anticoagulants and evaluating clinical scenarios, with evolving roles for anti-Xa assays, thrombin-based assays, and mass spectrometry techniques. Emerging anticoagulants targeting factors XI, XII, and XIII represent a promising future direction with the potential to further reduce bleeding risk while maintaining efficacy. Overall, continued advances in anticoagulant pharmacology, monitoring, and reversal strategies are driving a shift toward safer and more individualized patient care.</p>","PeriodicalId":12829,"journal":{"name":"Hematology Reports","volume":"18 5","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13600188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149030530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Concurrent Remission of Therapy-Related Acute Myeloid Leukemia and IgG-λ MGUS During Oral Decitabine-Cedazuridine: A Case Report.","authors":"Pasquale Niscola, Carla Mazzone, Marco Giovannini, Valentina Gianfelici, Maria Ilaria Del Principe","doi":"10.3390/hematolrep18050066","DOIUrl":"10.3390/hematolrep18050066","url":null,"abstract":"<p><p><b>Background and Clinical Relevance</b>: The association between acute myeloid leukemia (AML) and monoclonal gammopathy of undetermined significance (MGUS) is rare and likely coincidental, due to the similar epidemiology of these two blood disorders in older AML patients who are not eligible for intensive chemotherapy or aggressive treatment, as they can be excessively myelosuppressive. Such treatments include those containing venetoclax, an easy-to-use all-oral form of decitabine-cedazuridine (DEC-C), which is now available and approved for AML in addition to standard parenteral DNA methyltransferase inhibitors, which have been commonly used in routine clinical practice for about two decades in patients unsuitable for intensive chemotherapy (IC). <b>Case Presentation</b>: A 71-year-old woman developed a therapy-related acute myeloid leukemia (t-AML) seven years after the discovery of the plasma cell dyscrasia. She had carried an asymptomatic and non-progressing IgG-λ MGUS since 2019 while affected by breast cancer, which was cured with chemotherapy and radiotherapy. BM smear and trephine biopsy at the time of t-AML diagnosis showed 30% myelomonoblasts and 8% plasma cells, while SPEP showed the presence of 15 g/L of monoclonal protein. However, considering her age and other medical and personal history, the patient was found unsuitable for IC as well as venetoclax treatment because of the myelosuppressive effect of the therapy. Therefore, she received DEC-C oral monotherapy. After four DEC-C cycles, she achieved CR with hematological incomplete recovery (CRi). During DEC-C monotherapy, serum immunofixation (IF) and BM evaluations after 12 months of treatment showed gradual clearance of the IgG-λ paraprotein and BM plasma cells. Maintenance therapy with oral DEC-C is ongoing for 18 months after achieving CRi, without any signs of toxicity or infection. <b>Conclusions</b>: This report describes the first anecdotal case of t-AML responding to DEC-C with concomitant clearance of the paraprotein associated with MGUS.</p>","PeriodicalId":12829,"journal":{"name":"Hematology Reports","volume":"18 5","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13600068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149030466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Steatotic Liver Disease in Allogeneic Hematopoietic Stem Cell Transplant Recipients: A Case Series and Literature Review.","authors":"Karthik Chetlapalli, Clifford Shin, Stuart Seropian, Francine Foss, Iris Isufi, Sarah Perreault, Manoj Pillai, Amer Zeidan, Mahan Mathur, Noffar Bar, Charles Kenworthy, Gary Israel, Lohith Gowda","doi":"10.3390/hematolrep18050065","DOIUrl":"10.3390/hematolrep18050065","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Obesity and inflammatory conditions, including steatotic liver disease, are known to impact the hematopoietic niche and immune surveillance. Therefore, assessing the impact of steatotic liver disease on recipients of allogeneic stem cell transplantation (allo-HSCT) with bone marrow origin neoplasms is clinically relevant and an underexplored area of investigation. <b>Methods</b>: We followed the clinical course of allo-HSCT recipient patients with steatotic liver. <b>Results</b>: From 2014 to 2020 at our center, we identified 18 patients (5.8% of 306 patients screened) with steatotic liver disease detected on non-contrast CT imaging pre-transplant. With a minimum of 5 years follow-up for all, eight patients experienced post-transplant relapses (44%). Relapses (78%) followed by infections (55%) were the major contributors of mortality in this cohort. Pre-transplant transaminases were normal (AST median 28, ALT median 37) in all, while most patients (89%; 16/18) developed abnormal transaminases in the first-year post-transplantation without evidence of permanent liver injury. None experienced veno-occlusive disease of the liver. The cumulative incidence of acute graft-versus-host disease (aGVHD) was 33% (6/18), with 55% (10/18) experiencing chronic graft-versus-host disease (cGVHD). <b>Conclusions</b>: Our descriptive study highlights that radiologically detected steatotic liver disease is not a contraindication to proceeding with allogeneic stem cell transplant, and its association with transaminitis, relapse, immune complications, and post-transplant metabolic health requires future mechanistic studies.</p>","PeriodicalId":12829,"journal":{"name":"Hematology Reports","volume":"18 5","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13600020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149030248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ophelia-like Paraneoplastic Limbic Encephalitis with Haemorrhagic Temporal Lobe Involvement and Cauda Equina Dysfunction in Classical Hodgkin Lymphoma: A Case Report.","authors":"Abhishek Singla, Ritu Amit Chhabria, Michał Kurlapski, Michał Taszner, Jan Maciej Zaucha","doi":"10.3390/hematolrep18050064","DOIUrl":"10.3390/hematolrep18050064","url":null,"abstract":"<p><p>Ophelia syndrome is a rare paraneoplastic limbic encephalitis associated with classical Hodgkin lymphoma (cHL), most often with antibodies against metabotropic glutamate receptor 5 (mGluR5). We describe a 19-year-old man with newly diagnosed cHL who presented with generalised seizures, cognitive dysfunction, spastic paraparesis, cauda equina-related autonomic dysfunction, and a 35 × 31 mm haemorrhagic inflammatory lesion in the right temporal lobe. Brain biopsy showed dense intravascular and perivascular inflammatory infiltrates without neoplastic cells. Cerebrospinal fluid demonstrated pleocytosis and intrathecal IgG synthesis with type III oligoclonal bands. Serum and cerebrospinal fluid neuronal autoantibody panels were negative, but mGluR5 antibodies were not assessed. Cervical lymph node biopsy confirmed nodular sclerosis cHL, stage IIA. After exclusion of infectious encephalitis and central nervous system lymphoma, the presentation was considered most consistent with Ophelia-like paraneoplastic limbic encephalitis. ABVD chemotherapy was initiated, with rapid neurological improvement after the first cycle. Complete metabolic response was achieved after two cycles and sustained after six cycles. At 15-month follow-up, major neurological symptoms had not recurred, although bladder and bowel dysfunction persisted. This case highlights the importance of considering paraneoplastic limbic encephalitis in cHL despite negative standard neuronal antibody testing and of documenting whether mGluR5 antibodies were assessed.</p>","PeriodicalId":12829,"journal":{"name":"Hematology Reports","volume":"18 5","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13600170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149030240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metallothionein Isoforms in Acute Myeloid Leukemia: Roles in Survival, Differentiation, and Stress Adaptation.","authors":"Shinichiro Takahashi","doi":"10.3390/hematolrep18050062","DOIUrl":"10.3390/hematolrep18050062","url":null,"abstract":"<p><p>Metallothioneins (MTs) are cysteine-rich metal-binding proteins traditionally recognized for their roles in metal homeostasis and antioxidant defense. Recent studies have revealed broader and functionally diverse roles of MT isoforms in acute myeloid leukemia (AML). This review summarizes current evidence regarding MT-mediated regulation of leukemic cell survival, differentiation, and therapy-associated stress adaptation. MT1 family members, particularly MT1X and MT1G, have been associated with proliferation, chemoresistance, and differentiation blockade in specific experimental contexts, whereas MT2A and MT3 exhibit tumor-suppressive effects in selected AML models. MT isoforms also participate in oxidative stress adaptation and redox regulation, including responses to azacitidine, doxorubicin, and ferroptotic stress. However, the available evidence is derived largely from cell-line studies, selected molecular subtypes, transcriptomic analyses, and limited primary-patient datasets. Accordingly, isoform-specific MT functions should be interpreted as context-dependent rather than uniformly applicable across AML. Further validation in independent primary AML cohorts and genetically defined subtypes is required to establish their clinical utility as biomarkers or therapeutic targets.</p>","PeriodicalId":12829,"journal":{"name":"Hematology Reports","volume":"18 5","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13600175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149030243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Clinical and Hematological Markers of Pulmonary Embolism: Multicenter Retrospective Study in Mongolia.","authors":"Javzan-Orlom Dorjjugder, Munkh-Erdene Dashzeveg, Zolzaya Batbold, Amgalandari Byambabaatar, Altankhuyag Nergui, Enkh-Amgalan Tserendorj, Yerkyejan Dungyen, Badamsed Tserendorj, Tumur-Ochir Tsedev-Ochir, Batbold Batsaikhan, Solongo Bandi","doi":"10.3390/hematolrep18050063","DOIUrl":"10.3390/hematolrep18050063","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Systemic inflammation-derived indices, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII), have been proposed as convenient and cost-effective predictive markers of mortality and complications in patients with pulmonary embolism (PE). We aimed to evaluate the prognostic performance of hematological inflammatory indices for in-hospital adverse outcomes among Mongolian patients diagnosed with PE. <b>Methods</b>: This multicenter retrospective study enrolled patients admitted to three tertiary-level hospitals in Ulaanbaatar, Mongolia, with a confirmed diagnosis of PE between September 2019 and January 2025. Data were collected retrospectively from electronic medical records. We calculated the NLR, PLR, and SII using standard formulas. All patients were stratified according to the sPESI. Moreover, we determined the prognostic performance of hematological indices for in-hospital adverse events. <b>Results</b>: We analyzed information on 232 patients with a confirmed diagnosis of PE. According to sPESI scoring, 69.8% (162) were in the high-risk group, with significant differences in comorbidity and age over 60 years (<i>p</i> < 0.001). The most common symptoms were dyspnea, chest pain, cough, leg pain, and hemoptysis. The median NLR was 2.48 (1.66-5.08) in the low-risk group and 4.21 (2.04-11.35) in the high-risk group (<i>p</i> = 0.001). The median SII level was significantly higher in the high-risk group than in the low-risk group (<i>p</i> = 0.037). However, there was no significant difference in PLR level between the two study groups. ROC analysis of hematological indices for predicting in-hospital adverse outcomes was limited, with poor and non-significant discriminatory performance. <b>Conclusions</b>: In cases of acute pulmonary embolism, elevated inflammatory indices, NLR and SII, were associated with higher sPESI risk stratification. However, their probability to predict in-hospital adverse events was limited by ROC analysis.</p>","PeriodicalId":12829,"journal":{"name":"Hematology Reports","volume":"18 5","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13600193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149030246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Allogeneic Hematopoietic Stem Cell Transplantation in Myelofibrosis: Evolving Indications, Conditioning Strategies, and Outcomes.","authors":"Caterina Alati, Stefano Botti, Francesca Cogliandro, Martina Pitea, Matteo Pacilli, Gaetana Porto, Giorgia Policastro, Annalisa Sgarlata, Maria Caterina Mico, Barbara Loteta, Laura Giordano, Giulia Santoro, Jessyca Germano, Massimo Martino","doi":"10.3390/hematolrep18050061","DOIUrl":"10.3390/hematolrep18050061","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Myelofibrosis (MF) is a clonal myeloproliferative neoplasm driven by dysregulated JAK-STAT signaling, characterized by progressive marrow fibrosis, splenomegaly, constitutional symptoms, and increased risk of leukemic transformation. Allogeneic hematopoietic stem cell transplantation (allo-HCT) remains the only potentially curative intervention. In Italy, allo-HCTs for myeloproliferative neoplasms (MPN, i.e., myelofibrosis, polycythaemia vera, and essential thrombocythaemia combined) increased by 163% from 2015 to 2025; MF-specific procedure counts were not separately available in this registry export, so this figure should not be read as MF-specific, with MPN accounting for 8% of all allogeneic procedures (n = 171) in 2025, showing a 29.5% year-on-year increase from 2024. Concurrently, the demographic profile shifted, with individuals aged 60 and over representing 38% of all recipients, surpassing other age groups for the first time in 2025. <b>Results</b>: This review synthesizes current evidence on transplant indications and timing, pre-transplant management, donor selection, and conditioning regimen optimization, emphasizing the emerging role of treosulfan-based and dual-alkylator platforms, including the thiotepa-treosulfan-fludarabine (TTF) regimen. Post-transplant molecular MRD monitoring and relapse management are also discussed. Three-year overall survival in myelofibrosis ranges from about 59% to 67%, depending on donor type, with outcomes improving due to better patient selection, optimized conditioning, and supportive care. <b>Conclusions</b>: Prospective randomized trials are urgently needed to validate optimal conditioning intensity, the role of novel JAK inhibitors in the peri-transplant period, and MRD-guided pre-emptive strategies.</p>","PeriodicalId":12829,"journal":{"name":"Hematology Reports","volume":"18 5","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13600008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149030517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Narrative Review of Zinc Deficiency-Associated Anemia.","authors":"Karina Basmajian, Aren Dermarderosian, Ryan Jeffrey Thoreson, Joshua Adams, Camron Farjami, Austin Yang, Elham Akhtari, Soha Araji, Ziad Khan, Siamak Saadat, Sarkis Arabian, Christina Tansy, Gregory Knutzen, Mojtaba Akhtari","doi":"10.3390/hematolrep18040060","DOIUrl":"10.3390/hematolrep18040060","url":null,"abstract":"<p><p>Zinc is an essential micronutrient involved in many physiological processes in the human body, including immune system regulation, cellular survival, neurologic function, and erythropoiesis. Zinc deficiency can result in a wide range of clinical manifestations, including impaired immune function, dermatologic findings, and decreased growth. Anemia has been reported as a hematologic manifestation of zinc deficiency and may be underrecognized in clinical practice. This narrative review examines the pathophysiology of zinc deficiency-associated anemia, highlighting zinc's role in erythropoiesis, heme biosynthesis, and red blood cell stability. It also outlines populations at increased risk for zinc deficiency, including patients with chronic kidney disease, sickle cell disease, malabsorptive disorders, chronic proton pump inhibitor use, and older adults. Emerging evidence suggests that zinc deficiency-associated anemia may represent a potentially modifiable contributor to anemia in selected at-risk populations, although the strength of evidence varies across clinical settings and study designs. Assessment of zinc status may be considered in patients with unexplained or refractory anemia and additional risk factors for deficiency. Further prospective studies are needed to clarify the role of zinc deficiency in anemia and define appropriate screening, supplementation, and monitoring strategies.</p>","PeriodicalId":12829,"journal":{"name":"Hematology Reports","volume":"18 4","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13512597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148827249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The <i>CD70</i>/<i>CD27</i> Axis in Tyrosine Kinase Inhibitor-Treated Chronic Phase Chronic Myeloid Leukemia Cells Is Not an Achilles Heel.","authors":"Jennifer Cassels, Mark E Drotar, Alyson MacNeil, Michael W Moles, Ya-Ching Hsieh, Cassie J Clarke, Eoghan Forde, Lorna Jackson, Moira A Elliott, Julie Jacobs, Piotr Zabrocki, Mhairi Copland, Helen Wheadon, Alison M Michie, Heather G Jørgensen","doi":"10.3390/hematolrep18040059","DOIUrl":"10.3390/hematolrep18040059","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Revolutionary small molecule, targeted, tyrosine kinase inhibitors (TKIs) in the clinic have engendered the perception that optimal treatment has already been established for diseases like chronic myeloid leukemia (CML). Addressing <i>BCR::ABL1</i> oncokinase domain mutations in CML is unlikely to redress disease recrudescence owing to persistent leukemia stem cells (LSCs). Therefore, it is necessary to consider an alternative strategic approach: disrupting LSC interactions with the protective microenvironment and/or immune system. The interaction of the TNF-α superfamily member, <i>CD27</i>, with its upregulated ligand, <i>CD70</i>, initiates survival signaling specifically in CML cells when <i>BCR::ABL1</i> is inhibited by TKIs and thus represents an attractive target. Previous studies modulating the expression of <i>CD27</i> on LSCs in a mouse model of advanced phase CML were encouraging. In our study, we explored the <i>CD70</i>/<i>CD27</i> axis as a therapeutic target in early-phase disease. <b>Methods</b>: Primitive <i>CD34</i>+ cells from treatment-naïve chronic phase (CP) CML patients were drug-exposed in an in vitro co-culture system; combination drug treatments of the therapeutic anti-<i>CD70</i> antibody and TKIs, nilotinib, were assessed in our CP CML murine model. <b>Results</b>: The blockade of the <i>CD70</i>/<i>CD27</i> axis in combination with TKIs did not result in greater LSC elimination than with nilotinib as a single agent in our CP CML models. Nonetheless, there was an observed reduction in <i>CD70</i>+ cells with combination treatment. <b>Conclusion</b>: Further preclinical study of the antibody as an adjunct in <i>CD70</i>-expressing hematological malignancy is perhaps warranted.</p>","PeriodicalId":12829,"journal":{"name":"Hematology Reports","volume":"18 4","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13512372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148827480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}