Hematology, Transfusion and Cell Therapy最新文献

英文中文

Hypoxic conditions confer chemoresistance to crizotinib but not to imatinib in chronic myeloid leukemia cells 缺氧条件赋予慢性髓系白血病细胞对克唑替尼而非伊马替尼的化疗耐药

IF 1.6 Q3 HEMATOLOGY

Hematology, Transfusion and Cell Therapy

Pub Date : 2026-01-10 DOI: 10.1016/j.htct.2025.106240

Lena Avinery , Danielle Regev , Hazem Khamaisi , Jacob Gopas , Jamal Mahajna

Introduction

Chronic myeloid leukemia is an adult leukemia, constituting 15 % of all leukemia diagnoses. The fundamental driver of disease pathogenesis is the Bcr/Abl fusion protein, characterized by dysregulated tyrosine kinase activity. Abl kinase inhibitors have become the mainstay of treatment, however, patients often develop resistance due to genetic alterations, particularly affecting the Bcr/Abl oncoprotein. The tumor microenvironment is also associated with acquired resistance to Abl kinase inhibitors in chronic myeloid leukemia.

Methods

The influence of hypoxic conditions on the development of chemoresistance to certain Abl kinase inhibitors was investigated in chronic myeloid leukemia.

Results

This study showed that hypoxia increased resistance to crizotinib, while imatinib resistance was modest. Both drugs effectively inhibited Bcr/Abl activity. Interestingly, the JAK1/2 inhibitor ruxolitinib further enhanced chemoresistance to crizotinib under hypoxic conditions. Hypoxia-inducible factor 1α (HIF1α) overexpression in JAK2 knockdown experiments confirmed their cooperative role in mediating crizotinib resistance. In addition, 2-methoxyestradiol, a non-estrogenic estradiol metabolite, restored crizotinib sensitivity under hypoxia and the combination of 2-methoxyestradiol with a JAK2 inhibitor showed promising results in overcoming crizotinib resistance.

Conclusion

In summary, this study shows the critical role of selective targeting of components of the HIF1α signaling pathway for the complete eradication of chronic myeloid leukemia cells.

慢性髓系白血病是一种成人白血病，占所有白血病诊断的15% %。疾病发病的根本驱动因素是Bcr/Abl融合蛋白，其特征是酪氨酸激酶活性失调。Abl激酶抑制剂已成为治疗的主流，然而，由于基因改变，特别是影响Bcr/Abl癌蛋白，患者经常产生耐药性。肿瘤微环境也与慢性髓系白血病对Abl激酶抑制剂的获得性耐药有关。方法研究缺氧条件对慢性髓系白血病Abl激酶抑制剂耐药的影响。结果本研究显示，缺氧增加了对克唑替尼的抵抗，而对伊马替尼的抵抗是温和的。两种药物均有效抑制Bcr/Abl活性。有趣的是，JAK1/2抑制剂ruxolitinib在缺氧条件下进一步增强了对克里唑替尼的化学耐药。缺氧诱导因子1α (HIF1α)在JAK2敲低实验中的过表达证实了它们在介导克唑替尼耐药中的协同作用。此外，2-甲氧基yestradiol（一种非雌激素性雌二醇代谢物）在缺氧条件下恢复了对克唑替尼的敏感性，2-甲氧基yestradiol与JAK2抑制剂联合使用在克服克唑替尼耐药方面显示出良好的效果。综上所述，本研究表明选择性靶向HIF1α信号通路组分在完全根除慢性髓系白血病细胞中起着关键作用。

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引用次数: 0

Functional capacity in sickle cell disease: A pilot study with 1-minute sit-to-stand test 镰状细胞病的功能能力：一项1分钟坐立试验的试点研究

IF 1.6 Q3 HEMATOLOGY

Hematology, Transfusion and Cell Therapy

Pub Date : 2026-01-10 DOI: 10.1016/j.htct.2025.106230

Michele Barroso Thomaz , Lucas Fernandes Suassuna , Júlia Campos Fabri , Isabela de Oliveira Araújo , Júlia Carneiro Almeida , Daniela de Oliveira Werneck Rodrigues

Background

Sickle cell disease, the most prevalent monogenic recessive genetic disorder in the world, is characterized by two main pathogenic mechanisms: vaso-occlusion and hemolysis. These characteristics lead to reduced tolerance to physical exertion and, consequently, a reduced functional capacity which can be assessed using the one-minute sit-to-stand test. Complications from sickle cell disease result in poor quality of life, increased absenteeism from school and work, and impaired social interaction.

Method

Between January 2023 and April 2024, a pilot cross-sectional study was conducted with sickle cell disease patients aged from 18 to 60 years. The one-minute sit-to-stand test, Borg's perceived exertion scale, and the SF-36 quality of life questionnaire were utilized. Patients were monitored during the test. The sample was dichotomized based on test performance and SF-36 scores. Furthermore, clinical and demographic variables were analyzed.

Main results

Fifty-eight individuals participated in the final analysis. The mean age was 29.84 ± 11.20 years; 55.1 % were men, and 79.3 % identified themselves as Black or mixed race. The most prevalent genotype was hemoglobin SS (67.2 %), and 77.5 % were taking Hydroxyurea. The group with a better performance in the one-minute sit-to-stand test showed better quality of life as assessed using the SF-36 questionnaire.

Conclusion

Functional capacity is a significant factor in the autonomy and quality of life of patients with sickle cell disease. The one-minute sit-to-stand test is a low-cost and easily applicable test, which can contribute to the assessment of functional capacity in the routine follow-up of these patients.

镰状细胞病是世界上最常见的单基因隐性遗传病，其发病机制主要有两种：血管闭塞和溶血。这些特征导致对体力消耗的耐受性降低，从而导致功能能力下降，这可以通过一分钟坐立测试来评估。镰状细胞病的并发症导致生活质量差，缺勤率增加，社会交往受损。方法在2023年1月至2024年4月期间，对18至60岁的镰状细胞病患者进行了一项试点横断面研究。采用1分钟坐立测试、Borg劳累感知量表和SF-36生活质量问卷。在测试过程中对患者进行监测。根据测试成绩和SF-36分数对样本进行二分类。此外，还分析了临床和人口统计学变量。主要结果58人参与了最终的分析。平均年龄29.84±11.20岁；55.1%是男性，79.3%认为自己是黑人或混血儿。最常见的基因型是血红蛋白SS(67.2%)，服用羟脲的占77.5%。SF-36问卷调查显示，在一分钟坐立测试中表现较好的那一组表现出更好的生活质量。结论功能能力是影响镰状细胞病患者自主性和生活质量的重要因素。1分钟坐立测试是一种成本低且易于应用的测试，可以在这些患者的常规随访中评估功能能力。

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引用次数: 0

Acute fibrinous and organizing pneumonia after bone marrow transplantation, an underrecognized, severe condition 骨髓移植后急性纤维性和组织性肺炎，这是一种未被认识到的严重疾病

IF 1.6 Q3 HEMATOLOGY

Hematology, Transfusion and Cell Therapy

Pub Date : 2026-01-10 DOI: 10.1016/j.htct.2025.106238

Anita Cassoli Cortez , Maria Cristina Nunez Seiwald , Ana Rita Brito Medeiros da Fonseca , Aliana Meneses Ferreira , Gabriella Pogorzelski , Leonardo de Abreu Testagrossa , Yana Novis , André Nathan Costa

Introduction

Allogeneic bone marrow transplantation can lead to various pulmonary complications, including acute fibrinous organizing pneumonia. This condition is rare and presents with aggressive clinical features, distinct from other forms of organizing pneumonia, such as cryptogenic organizing pneumonia.

Method

A literature review using the PubMed, Embase, Lilacs, and Cochrane databases was conducted to analyze cases of acute fibrinous organizing pneumonia following transplantation focusing on clinical features, therapeutic approaches, and outcomes.

Case Report

The case of a 62-year-old female who developed acute fibrinous organizing pneumonia after transplantation for acute myeloid leukemia is presented. Despite an initial absence of infectious agents, parainfluenza virus was later identified in a bronchoalveolar lavage. The patient progressed to severe hypoxemic respiratory failure and was unresponsive to corticosteroids and rituximab, ultimately dying seven months post-transplant.

Conclusion

This is a rare and severe complication following allogeneic bone marrow transplantation. Early diagnosis, histopathological confirmation, and prompt initiation of corticosteroid therapy are critical for improving outcomes. Patients diagnosed before Day +100 generally have a better response to treatment and more favorable clinical outcomes. The need for a more effective and targeted treatment strategy remains an unmet challenge in managing this condition.

同种异体骨髓移植可导致多种肺部并发症，包括急性纤维性组织性肺炎。这种情况是罕见的，表现为侵袭性临床特征，不同于其他形式的组织性肺炎，如隐源性组织性肺炎。方法采用PubMed、Embase、Lilacs和Cochrane数据库进行文献综述，分析移植术后急性纤维性肺炎病例的临床特征、治疗方法和结局。病例报告：一位62岁女性在急性髓性白血病移植后出现急性纤维性组织肺炎。尽管最初没有感染因子，但后来在支气管肺泡灌洗中发现了副流感病毒。患者进展为严重低氧性呼吸衰竭，对皮质类固醇和利妥昔单抗无反应，最终在移植后7个月死亡。结论这是同种异体骨髓移植术后罕见而严重的并发症。早期诊断、组织病理学确认和及时开始皮质类固醇治疗对改善预后至关重要。在Day +100之前诊断的患者通常对治疗反应更好，临床结果更有利。需要更有效和更有针对性的治疗策略仍然是管理这种情况的一个未满足的挑战。

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引用次数: 0

Comment on “Risk factors associated with the use of red blood cells in elective cardiac surgeries” 对“选择性心脏手术中使用红细胞的相关危险因素”的评论

IF 1.6 Q3 HEMATOLOGY

Hematology, Transfusion and Cell Therapy

Pub Date : 2026-01-10 DOI: 10.1016/j.htct.2025.106236

Hinpetch Daungsupawong , Viroj Wiwanitkit

引用次数: 0

Association of the ABCB1 gene polymorphism C3435T (rs1045642) with acute myeloid leukemia: A genetic study ABCB1基因多态性C3435T （rs1045642）与急性髓性白血病的关联：一项遗传学研究

IF 1.6 Q3 HEMATOLOGY

Hematology, Transfusion and Cell Therapy

Pub Date : 2026-01-10 DOI: 10.1016/j.htct.2025.106239

Roh Ullah , Nazish Mazari , Ghulam Mustafa , Aisha Hameed , Shagufta Khaliq , Ali Amar , Faiz Ul Haq , Asif Haleem Khan , Asif Naveed

Introduction

The ATP Binding Cassette Subfamily B1 (ABCB1) gene is responsible for encoding the permeability glycoprotein (P-gp), a crucial protein involved in multidrug resistance. P-gp functions as an ATP-dependent efflux pump, actively removing diverse substances, including carcinogens, from cells. However, a specific genetic variation called the C3435T polymorphism of the ABCB1 gene has been linked to reduced plasma levels of P-gp substrates. This genetic variation leads to the accumulation of harmful compounds within cells, which may increase susceptibility to hematological malignancies. This study aims to determine the frequency of ABCB1 gene polymorphism C3435T (rs1045642) in acute myeloid leukemia patients at tertiary care hospitals in Lahore, Pakistan.

Methods

A cross-sectional comparative study was conducted to investigate the association between ABCB1 gene polymorphism (C3435T) and acute myeloid leukemia. A total of 100 samples (50 cases and 50 healthy controls) were genotyped using restriction fragment length polymorphism assay.

Results

The TT genotype of ABCB1 C3435T was more prevalent in cases (62%) compared to the control group (20%). In different genetic models, the TT genotype was significantly associated with acute myeloid leukemia when compared to the CC and CT genotypes.

Conclusion

This study suggests that the TT genotype of the ABCB1 C3435T gene polymorphism is more strongly associated with acute myeloid leukemia compared to controls. This specific genotype may contribute to the development or progression of this malignancy. Further research is needed to explore the functional implications of this genetic variation in the pathogenesis.

ATP结合盒亚家族B1 （ABCB1）基因负责编码通透性糖蛋白（P-gp）， P-gp是参与多药耐药的关键蛋白。P-gp作为atp依赖的外排泵，积极地从细胞中去除包括致癌物质在内的多种物质。然而，一种称为ABCB1基因C3435T多态性的特定遗传变异与血浆P-gp底物水平降低有关。这种遗传变异导致细胞内有害化合物的积累，这可能增加对血液恶性肿瘤的易感性。本研究旨在确定ABCB1基因多态性C3435T （rs1045642）在巴基斯坦拉合尔三级医院急性髓系白血病患者中的频率。方法：采用横断面对比研究ABCB1基因多态性（C3435T）与急性髓系白血病的相关性。采用限制性内切片段长度多态性法对100份样本（50例病例和50例健康对照）进行基因分型。结果：ABCB1 C3435T TT基因型在病例（62%）中较对照组（20%）更为普遍。在不同的遗传模型中，与CC和CT基因型相比，TT基因型与急性髓系白血病显著相关。结论：与对照组相比，ABCB1 C3435T基因多态性的TT基因型与急性髓系白血病的相关性更强。这种特定的基因型可能有助于这种恶性肿瘤的发生或进展。需要进一步的研究来探索这种遗传变异在发病机制中的功能意义。

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引用次数: 0

Comment on clinical characteristics and outcomes of non-tuberculous mycobacterial pulmonary infections after hematopoietic stem cell transplantation: A retrospective cohort study 造血干细胞移植后非结核性分枝杆菌肺部感染的临床特点和预后：一项回顾性队列研究

IF 1.6 Q3 HEMATOLOGY

Hematology, Transfusion and Cell Therapy

Pub Date : 2026-01-10 DOI: 10.1016/j.htct.2025.106090

Marhaba Khan, Tahir Abdul Qadir

引用次数: 0

Donor DNA: Embedding self-regulation into blood donation culture 献血者DNA：将自我调节融入献血文化。

IF 1.6 Q3 HEMATOLOGY

Hematology, Transfusion and Cell Therapy

Pub Date : 2026-01-10 DOI: 10.1016/j.htct.2025.106241

Dr RishiRaj Sinha

引用次数: 0

Drug development for sickle cell disease: repeated setbacks, yet there remains an optimistic outlook for future breakthroughs 镰状细胞病药物开发：屡遭挫折，但仍有乐观的前景，未来的突破。

IF 1.6 Q3 HEMATOLOGY

Hematology, Transfusion and Cell Therapy

Pub Date : 2026-01-01 DOI: 10.1016/j.htct.2025.106251

Rodolfo Cançado, Fernando Ferreira Costa

引用次数: 0

Mechanistic insights into the antiproliferative effect of the redox-active iron chelator Dp44mT on multiple myeloma cell lines 氧化还原活性铁螯合剂Dp44mT对多发性骨髓瘤细胞系抗增殖作用的机制研究

IF 1.6 Q3 HEMATOLOGY

Hematology, Transfusion and Cell Therapy

Pub Date : 2025-12-23 DOI: 10.1016/j.htct.2025.106233

Aarti Sharma , Latha Pathangey , Sinto Sebastian Chirackal , Kiran K. Mangalaparthi , Akhilesh Pandey , Rafael Fonseca , Sundararaman Swaminathan

Background

Impaired iron metabolism has been linked to the pathogenesis of multiple myeloma. Redox active iron chelators have gained attention as potential anti-cancer agents as they target the high iron dependency of cancer cells. This study explored the potential mechanisms underlying the anti-multiple myeloma effect of the redox active iron chelator Dp44mT (Di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone).

Methods

The effect of Dp44mT was tested on both immunomodulatory drug-sensitive and drug-resistant multiple myeloma cell lines using the MTT assay. Proteomic and phosphoproteomics characterization were utilized to explore the mechanisms of Dp44mT action on multiple myeloma cells. In addition, a real-time polymerase chain reaction assay was performed to examine the expressions of major iron metabolism genes. Reactive oxygen species, lipid peroxidation, mitochondrial membrane potential, and intracellular iron compartmentalization were measured using flow-cytometry.

Results

The high potency of Dp44mT in killing multiple myeloma cell lines was confirmed. Treatment with Dp44mT showed evidence of deregulated cellular iron metabolism, reactive oxygen species homeostasis, and mitochondrial membrane potential in multiple myeloma cell lines. As possible mechanistic pathways of Dp44mT, there was overrepresentation of the AMPK pathway, cell cycle, endoplasmic stress, and down regulation of ACSL4 (acyl-CoA synthetase long chain family member 4).

Conclusion

This study suggests an in vitro, anti-multiple myeloma effect of Dp44mT that appears to be mediated by dysregulated iron metabolism, reactive oxygen species, and other biological pathways.

背景：铁代谢受损与多发性骨髓瘤的发病机制有关。氧化还原活性铁螯合剂针对癌细胞的高铁依赖性，作为潜在的抗癌药物而受到关注。本研究探讨了氧化还原活性铁螯合剂Dp44mT（二-2-吡啶基酮4,4-二甲基-3-硫代氨基脲）抗多发性骨髓瘤作用的潜在机制。方法：采用MTT法检测Dp44mT对免疫调节药敏和耐药多发性骨髓瘤细胞株的影响。利用蛋白质组学和磷酸化蛋白质组学特性来探索Dp44mT对多发性骨髓瘤细胞的作用机制。此外，采用实时聚合酶链反应法检测主要铁代谢基因的表达。用流式细胞术测量活性氧、脂质过氧化、线粒体膜电位和细胞内铁区隔化。结果：证实了Dp44mT对多发性骨髓瘤细胞株的杀伤作用。在多发性骨髓瘤细胞系中，Dp44mT治疗显示细胞铁代谢、活性氧稳态和线粒体膜电位失调。作为Dp44mT可能的机制途径，AMPK途径、细胞周期、内质应激和ACSL4（酰基辅酶a合成酶长链家族成员4）下调被过度表达。结论：本研究提示Dp44mT的体外抗多发性骨髓瘤作用可能是由铁代谢失调、活性氧和其他生物学途径介导的。

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引用次数: 0

Plasma levels of soluble podoplanin are higher in acute promyelocytic leukemia compared to other forms of acute myeloid leukemia 与其他形式的急性髓细胞白血病相比，急性早幼粒细胞白血病的血浆可溶性足磷脂水平较高

IF 1.6 Q3 HEMATOLOGY

Hematology, Transfusion and Cell Therapy

Pub Date : 2025-12-19 DOI: 10.1016/j.htct.2025.106227

Carla Roberta Peachazepi Moraes , Camilla Maria de Alencar Saraiva , Ivanio Teixeira Borba-Junior , Bruno Kosa Lino Duarte , Paula Melo de Campos , Sara Teresinha Olalla Saad , Erich Vinicius De Paula

Background

Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML) marked by a high incidence of coagulopathy. Podoplanin, a glycoprotein involved in platelet activation through interaction with CLEC-2, has recently been identified on leukemic promyelocytes and suggested as a potential contributor to APL coagulopathy. Identification of novel biomarkers and therapeutic targets for APL coagulopathy can potentially improve the outcomes of this condition

Aim

To explore whether levels of soluble podoplanin in plasma are different in APL, and to evaluate its association with laboratory and clinical outcomes in these patients

Methods

Samples were obtained from consecutive patients with APL at the time of diagnosis in an academic hospital. Biobank samples from 35 patients with non-APL AML matched for age and sex were used as comparators. Circulating podoplanin levels were measured in plasma using a commercial ELISA kit. The study was approved by the institutional ethics committee and all participants provided written informed consent

Results

APL patients showed significantly higher plasma soluble podoplanin concentrations compared to non-APL AML. Using the median soluble podoplanin value as a cutoff, a higher proportion of APL patients presented elevated levels. Soluble podoplanin levels correlated with CD40L in APL cases, but not in non-APL AML patients, suggesting a possible interaction with thrombo-inflammatory activation pathways

Conclusion

These findings represent a proof-of-concept that measuring soluble podoplanin in plasma samples can contribute to the diagnosis of APL, while also providing novel data on the association of podoplanin with the pathogenesis of APL coagulopathy.

背景：急性早幼粒细胞白血病（APL）是急性髓性白血病（AML）的一种亚型，以凝血功能障碍的高发为特征。Podoplanin是一种通过与CLEC-2相互作用参与血小板活化的糖蛋白，最近在白血病早幼粒细胞中被发现，并被认为是APL凝血病的潜在因素。为了探讨APL患者血浆中可溶性足磷脂蛋白水平是否存在差异，并评估其与APL患者实验室和临床预后的关系。方法从一家学术医院诊断为APL的连续患者中获取样本。来自35名年龄和性别匹配的非apl AML患者的生物库样本作为比较物。血浆循环podoplanin水平用商用ELISA试剂盒测定。该研究获得了机构伦理委员会的批准，所有参与者都提供了书面知情同意书。结果：与非apl AML相比，apl患者的血浆可溶性podoplanin浓度显著升高。以可溶性足平面蛋白中位数作为截断值，更高比例的APL患者出现水平升高。在APL病例中，可溶性足磷脂蛋白水平与CD40L相关，而在非APL AML患者中则不相关，这表明可能与血栓炎症激活途径相互作用。结论这些发现证明了血浆样品中可溶性足磷脂蛋白的测定可以有助于APL的诊断，同时也为足磷脂蛋白与APL凝血病发病机制的关联提供了新的数据。

{"title":"Plasma levels of soluble podoplanin are higher in acute promyelocytic leukemia compared to other forms of acute myeloid leukemia","authors":"Carla Roberta Peachazepi Moraes , Camilla Maria de Alencar Saraiva , Ivanio Teixeira Borba-Junior , Bruno Kosa Lino Duarte , Paula Melo de Campos , Sara Teresinha Olalla Saad , Erich Vinicius De Paula","doi":"10.1016/j.htct.2025.106227","DOIUrl":"10.1016/j.htct.2025.106227","url":null,"abstract":"<div><h3>Background</h3><div>Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML) marked by a high incidence of coagulopathy. Podoplanin, a glycoprotein involved in platelet activation through interaction with CLEC-2, has recently been identified on leukemic promyelocytes and suggested as a potential contributor to APL coagulopathy. Identification of novel biomarkers and therapeutic targets for APL coagulopathy can potentially improve the outcomes of this condition</div></div><div><h3>Aim</h3><div>To explore whether levels of soluble podoplanin in plasma are different in APL, and to evaluate its association with laboratory and clinical outcomes in these patients</div></div><div><h3>Methods</h3><div>Samples were obtained from consecutive patients with APL at the time of diagnosis in an academic hospital. Biobank samples from 35 patients with non-APL AML matched for age and sex were used as comparators. Circulating podoplanin levels were measured in plasma using a commercial ELISA kit. The study was approved by the institutional ethics committee and all participants provided written informed consent</div></div><div><h3>Results</h3><div>APL patients showed significantly higher plasma soluble podoplanin concentrations compared to non-APL AML. Using the median soluble podoplanin value as a cutoff, a higher proportion of APL patients presented elevated levels. Soluble podoplanin levels correlated with CD40L in APL cases, but not in non-APL AML patients, suggesting a possible interaction with thrombo-inflammatory activation pathways</div></div><div><h3>Conclusion</h3><div>These findings represent a proof-of-concept that measuring soluble podoplanin in plasma samples can contribute to the diagnosis of APL, while also providing novel data on the association of podoplanin with the pathogenesis of APL coagulopathy.</div></div>","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":"48 1","pages":"Article 106227"},"PeriodicalIF":1.6,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145796937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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