Leukemia research最新文献

英文中文

Frequency and clinical impact of acute kidney injury in haploidentical hematopoietic cell transplantation with post-transplantation cyclophosphamide 单倍体造血细胞移植后环磷酰胺对急性肾损伤的发生率及临床影响

IF 2.2 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2025-11-26 DOI: 10.1016/j.leukres.2025.108143

Toshihide Endo , Hiromichi Takahashi , Takahiro Namiki, Yoshiyuki Hayashi, Shun Ito, Hironao Nukariya, Kazuya Kurihara, Takashi Koike, Yuuichi Takeuchi, Takashi Hamada, Kazuhide Iizuka, Shimon Otake, Masaru Nakagawa, Hideki Nakamura, Katsuhiro Miura

引用次数: 0

Neutropenic enterocolitis in acute myeloid leukemia: A nationwide inpatient cross-sectional study 急性髓性白血病中性粒细胞减少性小肠结肠炎：一项全国住院患者横断面研究

IF 2.2 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2025-11-25 DOI: 10.1016/j.leukres.2025.108142

Pragya Jain , Iqra Qazi , Jacob Thompson , Nency Ganatra , Shivam Patel , Pakeeza Saif , Junaid Anwar

Neutropenic enterocolitis (NE) is an uncommon but serious complication in patients with acute myeloid leukemia (AML), often arising during periods of myelosuppression. Although recognized clinically, its broader impact on hospitalization outcomes and healthcare utilization in AML is poorly defined. To evaluate the association between NE and key inpatient outcomes, including in-hospital mortality, length of stay (LOS), and total hospital charges among patients with AML, this retrospective cross-sectional analysis was performed using the Nationwide Inpatient Sample (NIS) from 2018 to 2022. Multivariable models were fitted using survey-weighted logistic regression for mortality and Poisson regression with a log link for LOS and charges, adjusting for demographic and clinical covariates to calculate adjusted odds ratios (aORs) and adjusted incidence rate ratios (aIRRs), with corresponding 95 % confidence intervals (CIs). Among an estimated 344,545 AML hospitalizations, 3865 involved NE, which were associated with significantly longer hospitalizations and higher costs. In adjusted models, NE increased LOS by nearly 50 % (aIRR: 1.47, 95 % CI: 1.41–1.54) and total charges by over 40 % (aIRR: 1.44, 95 % CI: 1.35–1.53), with both associations being highly significant (p < 0.0001). In contrast, NE was not independently associated with in-hospital mortality (aOR: 0.89, 95 % CI: 0.75–1.06; p = 0.20). This study's findings indicate that, though NE was not a predictor of mortality, it is a strong driver of healthcare utilization in patients hospitalized with AML. These findings underscore NE’s importance as a complication with major clinical and economic implications, highlighting the need for strategies to improve recognition and management in this vulnerable population.

中性粒细胞减少性小肠结肠炎（NE）是急性髓性白血病（AML）患者中一种罕见但严重的并发症，通常发生在骨髓抑制期间。虽然在临床上得到认可，但其对急性髓性白血病住院治疗结果和医疗保健利用的广泛影响尚不明确。为了评估NE与AML患者主要住院结局（包括住院死亡率、住院时间（LOS）和医院总收费）之间的关系，本研究使用2018年至2022年全国住院患者样本（NIS）进行了回顾性横断面分析。采用调查加权logistic回归拟合死亡率和泊松回归，对LOS和收费进行对数关联，调整人口统计学和临床协变量，计算调整优势比（aORs）和调整发病率比（aIRRs），相应的置信区间为95% % （ci）。在估计的344,545例急性髓性白血病住院中，3865例涉及NE，这与住院时间明显延长和费用较高相关。在调整后的模型中，NE使LOS增加了近50% % (aIRR: 1.47, 95 % CI: 1.41-1.54)，总收费增加了超过40% % (aIRR: 1.44, 95 % CI: 1.35-1.53)，两者的相关性都非常显著（p <； 0.0001）。相反，NE与住院死亡率没有独立相关性（aOR: 0.89, 95 % CI: 0.75-1.06; p = 0.20）。本研究的结果表明，虽然NE不是死亡率的预测因子，但它是急性髓性白血病住院患者医疗保健利用的强大驱动因素。这些发现强调了NE作为一种具有重大临床和经济意义的并发症的重要性，强调了在这一弱势群体中提高认识和管理策略的必要性。

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引用次数: 0

Genomic profiling reveals molecular heterogeneity in patients with Richter transformation (RT) and chronic lymphocytic leukemia (CLL) 基因组分析揭示里希特转化（RT）和慢性淋巴细胞白血病（CLL）患者的分子异质性

IF 2.2 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2025-11-11 DOI: 10.1016/j.leukres.2025.108133

Shulan Tian , Hanyin Wang , Sameer A. Parikh , Yuanhang Liu , Helen Jin-Lee , Erik Jessen , Eric W. Klee , Yucai Wang , Fan Leng , Min Shi , Cinthya Zepeda-Mendoza , Rong He , Saad J. Kenderian , Linda B. Baughn , Daniel L. Van Dyke , Paul J. Hampel , Neil E. Kay , Esteban Braggio , Susan L. Slager , Huihuang Yan , Wei Ding

Richter transformation (RT) represents the development of an aggressive lymphoma in chronic lymphocytic leukemia (CLL). Patients with RT and relapsed CLL have poor outcomes. Yet, the molecular differences between the two entities have not been fully explored. In this pilot study, we conducted RNA-seq and targeted panel sequencing of nodal tissues from 12 patients, including seven with RT and five with CLL. Analysis of RNA-seq data revealed two major clusters, with five RT in cluster C1 and the remaining two RT and all five CLL in C2. Within C2, one of the CLL ultimately developed RT; it showed more similarity to the two RT than to the other CLL in expression profile, suggesting the presence of expression signature for RT prior to the clinical diagnosis. In addition, differentially expressed genes, the majority of which showed higher expression in C1 relative to C2, were enriched in pathways known to be important for CLL pathogenesis or transformation. Deconvolution of the bulk RNA-seq data revealed major differences in cellular composition between the two clusters, notably tumor B cells, macrophages M1, and CD8 + T cells. Furthermore, by targeted sequencing, we identified 51 genes that carried recurrent copy number alterations (CNAs) preferentially occurring in either cluster. Over 80 % of these CNAs occurred in C2, mainly gains of 17q12q25 in CLL. Patients in C1 had shorter overall survival (median 11 months) compared to those in C2 (median 36 months). Together, our findings highlight noticeable differences in transcriptomic and genomic alterations between CLL versus RT.

里希特转化（RT）代表慢性淋巴细胞白血病（CLL）侵袭性淋巴瘤的发展。放疗和复发的CLL患者预后较差。然而，这两种实体之间的分子差异尚未得到充分探讨。在这项初步研究中，我们对12名患者的淋巴结组织进行了RNA-seq和靶向小组测序，其中包括7名RT患者和5名CLL患者。RNA-seq数据分析显示两个主要集群，C1集群中有5个RT， C2集群中其余2个RT和所有5个CLL。在C2内部，一个CLL最终开发了RT；在表达谱上，它与两种RT比与其他CLL更相似，表明在临床诊断之前存在RT的表达特征。此外，差异表达的基因，其中大多数在C1中相对于C2表达更高，在已知的CLL发病或转化的重要途径中富集。大量RNA-seq数据的反褶积揭示了两个集群之间细胞组成的主要差异，特别是肿瘤B细胞，巨噬细胞M1和CD8 + T细胞。此外，通过靶向测序，我们确定了51个基因携带复发性拷贝数改变（CNAs），优先发生在两个集群中。超过80% %的CNAs发生在C2，主要是CLL中17q12q25的增加。C1组患者的总生存期（中位11个月）短于C2组（中位36个月）。总之，我们的研究结果突出了CLL与RT之间转录组学和基因组改变的显著差异。

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引用次数: 0

NGS-based quantitative typing to identify HLA loss relapse after allogeneic stem cell transplantation 基于ngs的定量分型鉴定同种异体干细胞移植后HLA丢失复发。

IF 2.2 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2025-11-10 DOI: 10.1016/j.leukres.2025.108135

Kairi Kojo , Daichi Sadato , Takashi Toya , Keisuke Oboki , Chizuko Hirama, Yasumasa Nishito, Chika Kato, Hiroaki Shimizu, Kyoko Haraguchi, Hironori Harada, Yoshiki Okuyama, Yuka Harada, Noriko Doki, Yuho Najima

引用次数: 0

Differential impact of graft-versus-host disease on post-transplant outcomes of chronic myelomonocytic leukemia according to transplant procedures 根据移植程序，移植物抗宿主病对慢性髓细胞白血病移植后结果的差异影响。

IF 2.2 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2025-11-05 DOI: 10.1016/j.leukres.2025.108134

Hidehiro Itonaga , Yasushi Miyazaki , Machiko Fujioka , Shuhei Kurosawa , Yasunobu Nagata , Yutaka Shimazu , Tomoaki Ueda , Naoyuki Uchida , Noriko Doki , Tetsuya Nishida , Noboru Asada , Masatsugu Tanaka , Satoru Takada , Masatoshi Sakurai , Mineo Kurokawa , Makoto Yoshimitsu , Yoshinobu Kanda , Tatsuo Ichinohe , Yoshiko Atsuta , Takayoshi Tachibana

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) provides curative outcomes for chronic myelomonocytic leukemia (CMML). We conducted a retrospective study to clarify the protective impact of acute and chronic graft-versus-host disease (aGVHD and cGVHD) on relapse by transplant procedures in 314 CMML patients. Interaction effects of conditioning intensity were observed with aGVHD (P_interaction=0.181) and cGVHD (P_interaction=0.256) for the cumulative incidence of relapse (CIR), whereas interaction effects of donor type were not detected with GVHD. In patients with the myeloablative conditioning regimens, the multivariate analysis showed that the development of aGVHD was not associated with overall survival (OS). The development of limited cGVHD correlated with better OS (HR [95 % CI], 0.34 [0.14–0.81]; P = 0.015); and that of extensive cGVHD correlated with better OS (HR, 0.44 [0.21–0.91]; P = 0.026) and lower CIR (HR, 0.28 [0.08–0.94]; P = 0.040). In patients with the reduced-intensity conditioning regimens, the development of grade I-II aGVHD correlated with better OS (HR, 0.39 [0.20–0.76]; P = 0.005) and lower CIR (HR, 0.30 [0.13–0.70]; P = 0.006). The development of extensive cGVHD correlated with better OS (HR, 0.44 [0.20–0.96]; P = 0.039). The present results suggest that the type and severity of GVHD mediating graft-versus-leukemia effects against relapse were influenced by conditioning intensity in CMML patients.

同种异体造血干细胞移植（alloo - hsct）为慢性髓细胞白血病（CMML）提供了治疗效果。我们进行了一项回顾性研究，以阐明急性和慢性移植物抗宿主病（aGVHD和cGVHD）对314例CMML患者移植手术复发的保护作用。调节强度与aGVHD （Pinteraction=0.181）和cGVHD （Pinteraction=0.256）对累积复发率（CIR）的交互作用，而供体类型与GVHD的交互作用未检测到。在接受清髓调节方案的患者中，多因素分析显示，aGVHD的发展与总生存期（OS）无关。局限性cGVHD的发展与较好的OS相关（HR[95 % CI], 0.34 [0.14-0.81]; P = 0.015）；广泛cGVHD与较好的OS （HR, 0.44 [0.21-0.91]; P = 0.026）和较低的CIR （HR, 0.28 [0.08-0.94]; P = 0.040）相关。在低强度调节方案的患者中，I-II级aGVHD的发展与更好的OS （HR, 0.39 [0.20-0.76]; P = 0.005）和更低的CIR （HR, 0.30 [0.13-0.70]; P = 0.006）相关。广泛cGVHD的发展与较好的OS相关（HR, 0.44 [0.20-0.96]; P = 0.039）。目前的结果表明，GVHD介导的移植物抗白血病复发效应的类型和严重程度受CMML患者调节强度的影响。

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引用次数: 0

Corrigendum to “CircPAN3 contributes to drug resistance in acute myeloid leukemia through regulation of autophagy” [Leuk. Res., 85 (2019) 106198] “CircPAN3通过调节自噬参与急性髓系白血病的耐药”的更正[Leuk]。Res., 85(2019) 106198]。

IF 2.2 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2025-11-01 DOI: 10.1016/j.leukres.2025.108111

Jin Shang, Wei-Min Chen, Shan Liu, Zhi-Hong Wang, Tian-Nan Wei, Zhi-Zhong Chen, Wen-Bing Wu

引用次数: 0

Corrigendum to “The SMAC mimetic RMT5265.2HCL induces apoptosis in EBV and HTLV-I associated lymphoma cells by inhibiting XIAP and promoting the mitochondrial release of cytochrome C and SMAC” [Leuk. Res., 36(2011) 784–90] “SMAC模拟物RMT5265.2HCL通过抑制XIAP和促进线粒体细胞色素C和SMAC的释放诱导EBV和HTLV-I相关淋巴瘤细胞凋亡”[Leuk]的更正。Res., 36(2011) 784-90]。

IF 2.2 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2025-11-01 DOI: 10.1016/j.leukres.2025.108115

Sampath Ramachandiran, Joan Cain, Albert Liao, Yanjuan He, Xiangxue Guo, Lawrence H. Boise, Haian Fu, Lee Ratner, Hanna Jean Khoury, Leon Bernal-Mizrachi

引用次数: 0

Rusfertide rapidly decreases hematocrit in patients with suboptimally controlled polycythemia vera Rusfertide能迅速降低真性红细胞增多症患者的红细胞压积

IF 2.2 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2025-10-29 DOI: 10.1016/j.leukres.2025.108132

Lee Ping Chew , Yelena Z. Ginzburg , Kamini Kirubamoorthy , Sung-Eun Lee , Jae Hoon Lee , Nishit B. Modi , Sarita Khanna , Phillip Dinh , Frank Valone , Arturo Molina , Suneel Gupta

Polycythemia vera (PV) is characterized by overproduction of erythrocytes, leukocytes, and platelets. Rusfertide is a hepcidin mimetic polypeptide that binds to ferroportin and decreases iron delivery to bone marrow, reducing the production of red blood cells. The primary objective of this study was to evaluate the efficacy and safety of rusfertide in patients with PV and elevated (>48 %) baseline hematocrit. Patients were treated with 40 mg subcutaneous rusfertide twice weekly until their hematocrit reached < 45 %; once achieved, patients received weekly rusfertide dosing. Of the 20 patients enrolled, 15 (75 %) completed 24 weeks of treatment, 13 (65 %) completed 52 weeks, and 7 discontinued rusfertide therapy. Mean baseline hematocrit was 51.6 %. By Week 8, 17 (85 %) patients achieved hematocrit < 45 %, and 19 (95 %) achieved ≥ 5 % absolute reduction from baseline. Median time to first hematocrit < 45 % was 4.9 weeks. Mean hematocrit was < 45 % at Week 4 and subsequently remained < 45 % throughout the study. No patients received phlebotomy during rusfertide treatment. Rusfertide led to a significant reduction in erythrocyte count (5.98 ×10¹²/L to 4.79 ×10¹²/L; nominal p-value 0.0036) and an improvement in iron deficiency markers (eg, ferritin and mean corpuscular volume) relative to baseline. Seventeen patients (85 %) experienced treatment-emergent adverse events, most of which were Grade 1/2. In this open-label phase 2 study, rusfertide resulted in a rapid and sustained improvement in hematocrit and was generally well tolerated. Rapid and sustained control of hematocrit reduces the need for therapeutic phlebotomy and may help reduce thrombotic and cardiovascular events over the long term in patients with PV.

真性红细胞增多症（PV）的特点是红细胞、白细胞和血小板的过量产生。Rusfertide是一种模拟hepcidin的多肽，它与铁转运蛋白结合，减少铁向骨髓的输送，减少红细胞的产生。本研究的主要目的是评估rusfertide对PV和基线血细胞比容升高（> 48% %）患者的疗效和安全性。患者接受40 mg皮下rusfertide治疗，每周2次，直到其红细胞比容达到<； 45 %；一旦达到，患者每周接受rusfertide剂量。在入选的20名患者中，15名（75 %）完成了24周的治疗，13名（65 %）完成了52周的治疗，7名停止了rusfertide治疗。平均基线血细胞比容为51.6 %。到第8周，17例（85 %）患者的血细胞比容达到 45 %，19例（95 %）患者的绝对比基线降低≥ 5 %。至首次红细胞压积<； 45 %的中位时间为4.9周。在第4周，平均血细胞比容为<； 45 %，随后在整个研究过程中保持<； 45 %。在rusfertide治疗期间，没有患者接受静脉切开术。Rusfertide导致红细胞计数显著降低（5.98 ×1012/L至4.79 ×1012/L；名义p值0.0036），铁缺乏标志物（例如，铁蛋白和平均红细胞体积）相对于基线有所改善。17例患者（85% %）出现治疗后出现的不良事件，大多数为1/2级。在这项开放标签的2期研究中，rusfertide导致红细胞压积的快速和持续改善，并且通常耐受性良好。快速和持续的控制红细胞压积减少了治疗性静脉切开术的需要，并可能有助于减少PV患者的血栓和心血管事件。

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引用次数: 0

High JAK2V617F allele burden in low-risk PV: an additional recommendation to start “early” cytoreduction? Results from a multicentric study 低风险PV患者JAK2V617F等位基因负担高：“早期”细胞减少的额外建议？来自多中心研究的结果。

IF 2.2 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2025-10-22 DOI: 10.1016/j.leukres.2025.108123

Luca Tosoni, Sara Di Giusto, Gianluca Morelli, Melissa Bergnach, Chiara Callegari, Rossella Stella, Francesco Zaja, Antonia Schwab, Albert Wölfler, Eleonora Toffoletti, Daniela Damiani, Renato Fanin, Mario Tiribelli

引用次数: 0

Exosomal miR-140–3p produced by bone marrow stromal cells affects acute myeloid leukemia cell growth and apoptosis by targeting SUZ12 骨髓基质细胞产生的外泌体miR-140-3p通过靶向SUZ12影响急性髓系白血病细胞的生长和凋亡

IF 2.2 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2025-10-16 DOI: 10.1016/j.leukres.2025.108122

Jiajia Li , Feifan Li , Mengmeng Zhang , Yanping Wu , Meng Wang , Pingping Zhang

There is growing evidence that exosomes produced by bone marrow stromal cells (BMSCs) are associated with the progression of several cancers, including acute myeloid leukemia (AML), but intrinsic molecular mechanisms remain elusive. Here, we applied previous microarray analysis (GSE133276 and GSE209871) to identify differentially expressed exosomal miRNAs in BMSCs of AML patients, and candidate miR-140–3p, miR-142–5p and miR-142–3p were selected. This study aimed to investigate whether BMSCs affects AML progression are mediated by the candidates, and to explore regulatory mechanisms. The levels of the candidates were examined in bone marrow and BMSCs from AML patients, and exosomes from BMSCs of normal subjects and AML cells by qRT-PCR. Cell proliferation and apoptosis of AML cells co-cultured with BMSCs were detected through CCK-8, colony formation, flow cytometry, and Caspase-3 activity assays with manipulation of the candidate miRNAs expression. RNA pull-down and luciferase reporter assays to identify the downstream target mRNAs of the miRNAs. We confirmed that miR-140–3p, miR-142–5p and miR-142–3p levels were downregulated in bone marrow and BMSCs of AML patients, and were significantly enriched in exosomes of BMSCs but not AML cells. BMSCs co-cultured with AML cells could transfer these miRNAs into AML cells, and suppressed the proliferative potential and promoted the apoptotic behavior of AML cells. Furthermore, miR-140–3p agomir in BMSCs exacerbated the effects of the co-culture system on the AML cell proliferation and apoptosis, which were attenuated by miR-140–3p antagomir. In contrast, co-culture data showed that miR-142–5p and miR-142–3p had no significant effect on cell proliferation and apoptosis. Moreover, SUZ12 polycomb repressive complex 2 subunit (SUZ12) was directly targeted by miR-140–3p, overexpression or inhibition of SUZ12 in AML cells partially counteracted miR-140–3p agomir or antagomir-mediated cellular effects, respectively. Our study suggested that the BMSCs-derived exosomal miR-140–3p, rather than miR-142–5p and miR-142–3p, has a regulatory effect on the growth and apoptosis of AML cells by targeting SUZ12.

越来越多的证据表明，骨髓基质细胞（BMSCs）产生的外泌体与包括急性髓性白血病（AML）在内的几种癌症的进展有关，但其内在的分子机制尚不清楚。在这里，我们应用先前的微阵列分析（GSE133276和GSE209871）来鉴定AML患者骨髓间质干细胞中差异表达的外泌体mirna，并选择候选miR-140-3p， miR-142-5p和miR-142-3p。本研究旨在探讨骨髓间充质干细胞影响AML进展是否由候选药物介导，并探讨其调控机制。通过qRT-PCR检测候选蛋白在AML患者骨髓和骨髓间充质干细胞中的水平，以及正常受试者骨髓间充质干细胞和AML细胞的外泌体中的水平。通过CCK-8、集落形成、流式细胞术和Caspase-3活性测定以及操纵候选miRNAs的表达，检测AML细胞与BMSCs共培养的细胞增殖和凋亡。RNA下拉和荧光素酶报告基因检测鉴定mirna的下游靶mrna。我们证实，miR-140-3p、miR-142-5p和miR-142-3p水平在AML患者骨髓和骨髓间充质干细胞中下调，在骨髓间充质干细胞外泌体中显著富集，而在AML细胞中不富集。骨髓间充质干细胞与AML细胞共培养可将这些mirna转移到AML细胞中，抑制AML细胞的增殖潜能，促进AML细胞的凋亡行为。此外，BMSCs中的miR-140-3p阿塔戈米尔加重了共培养系统对AML细胞增殖和凋亡的影响，miR-140-3p阿塔戈米尔可以减弱这种影响。相比之下，共培养数据显示miR-142-5p和miR-142-3p对细胞增殖和凋亡无显著影响。此外，miR-140-3p直接靶向了SUZ12多梳抑制复合物2亚基（SUZ12）， AML细胞中SUZ12的过表达或抑制分别部分抵消了miR-140-3p agomir或antagomir介导的细胞效应。我们的研究表明，bmscs来源的外泌体miR-140-3p，而不是miR-142-5p和miR-142-3p，通过靶向SUZ12对AML细胞的生长和凋亡具有调节作用。

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