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TTMV::RARA-positive acute promyelocytic leukemia with marrow necrosis and central nervous system involvement at disease recurrence. TTMV::RARA阳性急性早幼粒细胞白血病复发时伴有骨髓坏死和中枢神经系统受累。
IF 0.9 Q4 HEMATOLOGY Pub Date : 2024-01-01 DOI: 10.3960/jslrt.24015
Zhao Wang, Jiaqi Chen, Juanxia Meng, Mingfeng Zhao, Hongxing Liu, Xia Xiao

Since the identification of the TTMV::RARA fusion in pediatric cases resembling acute promyelocytic leukemia (APL) by Astolfi et al. in 2021, several similar cases have been reported worldwide. In this report, we present a case of relapsed APL in an adolescent patient, who exhibited the TTMV::RARA fusion gene. This patient exhibited extensive central nervous system involvement and experienced bone marrow necrosis during disease recurrence. Despite achieving complete remission after re-induction chemotherapy, the patient experienced a rapid second relapse, highlighting the extremely aggressive nature of this subtype. These clinical manifestations contribute to the growing recognition of this rare disease.

自2021年Astolfi等人在类似急性早幼粒细胞白血病(APL)的儿科病例中发现TTMV::RARA融合基因以来,全球已有多例类似病例报道。在本报告中,我们介绍了一例青少年 APL 复发病例,患者携带 TTMV::RARA 融合基因。该患者表现出广泛的中枢神经系统受累,并在疾病复发期间出现骨髓坏死。尽管患者在再次接受化疗后病情得到完全缓解,但很快又再次复发,这凸显了该亚型极具侵袭性的特点。这些临床表现使人们对这种罕见疾病的认识不断提高。
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引用次数: 0
Salivary gland swelling as a characteristic manifestation of local cytokine release syndrome after anti-CD19 chimeric antigen receptor T cell therapy: A case series. 唾液腺肿胀是抗 CD19 嵌合抗原受体 T 细胞治疗后局部细胞因子释放综合征的特征性表现:病例系列。
IF 0.9 Q4 HEMATOLOGY Pub Date : 2024-01-01 DOI: 10.3960/jslrt.24035
Saki Kawase, Masatoshi Sakurai, Kyoko Masuda, Yusuke Kubota, Takahide Shindo, Ami Inokuchi, Hiroyoshi Hayashi, Misa Nakayasu, Yuka Shiozawa, Tomohiro Hirai, Takahiro Inoue, Takayuki Fujii, Haryoon Kim, Yuya Koda, Jun Kato, Keisuke Kataoka

Cytokine release syndrome (CRS) is the most common adverse event of chimeric antigen receptor T (CAR-T) cell therapy and is usually characterized by systemic symptoms such as fever, hypotension, and hypoxia. However, there have been several recent reports of local CRS characterized by cervical swelling. This localized syndrome can cause life-threatening laryngeal edema and requires early diagnostic treatment. Here we report 3 cases of local CRS where bilateral salivary gland swelling emerged following anti-CD19 CAR-T cell therapy for relapsed or refractory diffuse large B-cell lymphoma. Following tocilizumab treatment for systemic CRS, all patients exhibited cervical swelling. Physical examinations revealed significant swelling of the bilateral submandibular glands, and computed tomography scans showed substantial enlargement of the bilateral parotid and submandibular glands. Immediate treatment with dexamethasone effectively managed the potentially life-threatening laryngeal or pharyngeal edema, thereby preventing severe airway obstruction. This study has demonstrated, for the first time to our knowledge, that salivary gland enlargement is a common finding in local CRS. This observation suggests that physicians should continue to closely monitor the risk of developing cervical edema leading to life-threatening airway obstruction after systemic CRS, even in patients treated with tocilizumab. If salivary gland swelling is observed, it would be better to consider prompt evaluation and dexamethasone administration.

细胞因子释放综合征(CRS)是嵌合抗原受体 T(CAR-T)细胞疗法最常见的不良反应,通常以发热、低血压和缺氧等全身症状为特征。不过,最近也有一些关于以颈部肿胀为特征的局部 CRS 的报道。这种局部综合征可导致喉头水肿,危及生命,需要及早诊断治疗。在此,我们报告了3例局部CRS病例,患者在接受抗CD19 CAR-T细胞治疗复发或难治性弥漫大B细胞淋巴瘤后出现双侧唾液腺肿胀。托珠单抗治疗全身性CRS后,所有患者都出现了颈部肿胀。体格检查显示双侧颌下腺明显肿大,计算机断层扫描显示双侧腮腺和颌下腺显著肿大。立即使用地塞米松治疗有效地控制了可能危及生命的喉或咽水肿,从而避免了严重的气道阻塞。据我们所知,这项研究首次证明唾液腺肿大是局部 CRS 的常见症状。这一观察结果表明,医生应继续密切监测全身性 CRS 后发生颈部水肿导致危及生命的气道阻塞的风险,即使是接受托珠单抗治疗的患者也不例外。如果观察到唾液腺肿胀,最好考虑及时评估并使用地塞米松。
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引用次数: 0
Real-world outcomes of venetoclax and rituximab for chronic lymphocytic leukemia/small lymphocytic lymphoma: A retrospective analysis of nine Japanese cases. Venetoclax 和利妥昔单抗治疗慢性淋巴细胞白血病/小淋巴细胞淋巴瘤的实际效果:九例日本病例的回顾性分析。
IF 0.9 Q4 HEMATOLOGY Pub Date : 2024-01-01 DOI: 10.3960/jslrt.24014
Masuho Saburi, Takumi Nishikawa, Yasuhiko Miyazaki, Kazuhiro Kohno, Masanori Sakata, Kazuki Okuhiro, Toshiyuki Nakayama, Eiichi Ohtsuka, Masao Ogata
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引用次数: 0
Highlights: Myeloid cells in lymphoid malignancies. 重点:淋巴恶性肿瘤中的髓系细胞。
IF 0.9 Q4 HEMATOLOGY Pub Date : 2024-01-01 DOI: 10.3960/jslrt.24076
Yoshihiro Komohara
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引用次数: 0
Computed tomography findings of idiopathic multicentric Castleman disease subtypes. 特发性多中心Castleman病亚型的计算机断层扫描表现。
IF 0.9 Q4 HEMATOLOGY Pub Date : 2024-01-01 DOI: 10.3960/jslrt.24053
Toshihiro Iguchi, Asami Nishikori, Yasuharu Sato, Midori Filiz Nishimura, Noriko Iwaki, Katsuhide Kojima, Takashi Asahara, Fumio Otsuka, Yoshinobu Maeda, Takao Hiraki

This study retrospectively evaluated the computed tomography (CT) findings of idiopathic multicentric Castleman disease (iMCD) at a single center and compared the CT findings of iMCD-TAFRO with those of iMCD-non-TAFRO. CT images obtained within 30 days before diagnostic confirmation were reviewed for 20 patients with iMCD (8 men and 12 women, mean age 52.8 ± 12.3 years, range 25-74 years). Twelve patients were diagnosed with iMCD-TAFRO, five with iMCD-idiopathic plasmacytic lymphadenopathy, and three with iMCD-not otherwise specified. CT images revealed anasarca and lymphadenopathy in all 20 patients. The iMCD-TAFRO group showed significantly higher frequencies of ascites (100% vs. 37.5%, P = 0.004), gallbladder wall edema (75.0% vs. 12.5%, P = 0.020), periportal collar (91.7% vs. 25.0%, P = 0.004), and anterior mediastinal lesions (non-mass-forming infiltrative lesions) (66.7% vs. 12.5%, P = 0.028). Para-aortic edema tended to be more frequent in patients with the iMCD-TAFRO group (83.3% vs. 37.5%, P = 0.062), while the absence of anterior mediastinal lesions tended to be more frequent in the iMCD-non-TAFRO group (16.7% vs. 62.5%, P = 0.062). These CT findings may have clinical implications for improving the accuracy and speed of iMCD diagnosis and differentiating iMCD-TAFRO from other subtypes.

本研究回顾性评价了特发性多中心Castleman病(iMCD)在单中心的CT表现,并比较了iMCD- tafro和iMCD-非tafro的CT表现。回顾性分析20例iMCD患者(男8例,女12例,平均年龄52.8±12.3岁,年龄范围25-74岁)确诊前30天内的CT图像。12名患者被诊断为iMCD-TAFRO, 5名被诊断为imcd -特发性浆细胞性淋巴结病,3名被诊断为imcd -未另行说明。20例患者CT表现均为无影及淋巴结肿大。iMCD-TAFRO组出现腹水(100% vs. 37.5%, P = 0.004)、胆囊壁水肿(75.0% vs. 12.5%, P = 0.020)、门静脉周围颈环(91.7% vs. 25.0%, P = 0.004)和前纵隔病变(非团块形成的浸润性病变)(66.7% vs. 12.5%, P = 0.028)的频率显著高于tafro组。iMCD-TAFRO组患者主动脉旁水肿发生率更高(83.3%比37.5%,P = 0.062),而imcd -非tafro组前纵隔无病变发生率更高(16.7%比62.5%,P = 0.062)。这些CT表现可能对提高iMCD诊断的准确性和速度以及将iMCD- tafro与其他亚型区分开来具有临床意义。
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引用次数: 0
Insulin-like growth factor II mRNA binding protein 3 is highly expressed in primary diffuse large B-cell lymphoma of the CNS. 胰岛素样生长因子 II mRNA 结合蛋白 3 在中枢神经系统原发性弥漫大 B 细胞淋巴瘤中高度表达。
IF 0.9 Q4 HEMATOLOGY Pub Date : 2024-01-01 DOI: 10.3960/jslrt.24025
Kentaro Odani, Masakazu Fujimoto, Hirotake Fujii, Manduwa Saka, Kai Mizoguchi, Masahiro Hirata, Takaki Sakurai, Yasuhide Takeuchi, Sachiko Minamiguchi, Yoshiki Arakawa, Hironori Haga

Primary diffuse large B-cell lymphoma of the central nervous system (CNS-DLBCL) can be difficult to diagnose because of the limited amount of biopsy tissue. Here, we analyzed the utility of insulin-like growth factor II mRNA binding protein 3 (IMP3) immunohistochemistry (IHC) as an adjunctive diagnostic tool for CNS-DLBCL. IHC was performed on 57 biopsy samples (55 brain biopsy samples and two vitreous cell blocks) from 54 patients with CNS-DLBCL, including three biopsy samples initially diagnosed as negative or indeterminate for CNS-DLBCL. Additionally, IMP3 IHC was performed on 68 DLBCLs other than CNS-DLBCL and 12 inflammatory brain diseases. Cytoplasmic IMP3 expression was noted in ≥50% of tumor cells in 100% (57/57) of CNS-DLBCLs and 88.2% (60/68) of non-CNS-DLBCLs. In contrast, no IMP3-positive CD20-positive B cells were observed in the inflammatory brain disease (P < 0.0001). In conclusion, IMP3 is highly expressed in CNS-DLBCL. However, it is also expressed in other types of DLBCLs, making it less specific. Most CNS-DLBCL cases can be diagnosed without performing IHC for IMP3 expression, but it may be a useful adjunctive tool to differentiate from reactive lesions when tumor cells are few or deformed.

中枢神经系统原发性弥漫大B细胞淋巴瘤(CNS-DLBCL)因活检组织量有限而难以诊断。在此,我们分析了胰岛素样生长因子 II mRNA 结合蛋白 3(IMP3)免疫组织化学(IHC)作为中枢神经系统弥漫性大 B 细胞淋巴瘤辅助诊断工具的实用性。对 54 名 CNS-DLBCL 患者的 57 份活检样本(55 份脑活检样本和 2 份玻璃体细胞块)进行了 IHC 检测,其中包括 3 份最初诊断为阴性或不确定为 CNS-DLBCL 的活检样本。此外,还对 68 例 CNS-DLBCL 以外的 DLBCL 和 12 例脑部炎症性疾病进行了 IMP3 IHC 检测。在100%(57/57)的中枢神经系统-DLBCL和88.2%(60/68)的非中枢神经系统-DLBCL中,≥50%的肿瘤细胞有胞质IMP3表达。相比之下,在脑部炎症性疾病中未观察到 IMP3 阳性 CD20 阳性 B 细胞(P < 0.0001)。总之,IMP3 在中枢神经系统-DLBCL 中高度表达。然而,它在其他类型的 DLBCL 中也有表达,因此特异性较低。大多数中枢神经系统-DLBCL病例无需进行IMP3表达的IHC检查即可确诊,但当肿瘤细胞较少或变形时,IMP3可能是区分反应性病变的有用辅助工具。
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引用次数: 0
Frequent CDKN2B/P15 and DAPK1 methylation in duodenal follicular lymphoma is related to duodenal reactive lymphoid hyperplasia. 十二指肠滤泡淋巴瘤中CDKN2B/P15和DAPK1的频繁甲基化与十二指肠反应性淋巴增生有关。
IF 0.9 Q4 HEMATOLOGY Pub Date : 2024-01-01 DOI: 10.3960/jslrt.24020
Katsuyoshi Takata, Tomoko Miyata-Takata, Yasuharu Sato

Duodenal type follicular lymphoma (DFL), a rare entity of follicular lymphoma (FL), is clinically indolent and is characterized by a low histological grade compared with nodal follicular lymphoma (NFL). Our previous reports revealed that DFL shares characteristics of both NFL and mucosa-associated lymphoid tissue (MALT) lymphoma in terms of clinical and biological aspects, suggesting its pathogenesis may involve antigenic stimulation. In contrast to NFL, the genomic methylation status of DFL is still challenging. Here, we determined the methylation profiles of DNAs from patients with DFL (n = 12), NFL (n = 10), duodenal reactive lymphoid hyperplasia (D-RLH) (n = 7), nodal reactive lymphoid hyperplasia (N-RLH) (n = 5), and duodenal samples from normal subjects (NDU) (n = 5) using methylation specific PCR of targets previously identified in MALT lymphoma (CDKN2B/P15, CDKN2A/P16, CDKN2C/P18, MGMT, hMLH-1, TP73, DAPK, HCAD). DAPK1 was frequently methylated in DFL (9/12; 75%), NFL (9/10; 90%), and D-RLH (5/7; 71%). CDKN2B/P15 sequences were methylated in six DFL samples and in only one NFL sample. Immunohistochemical analysis showed that p15 expression inversely correlated with methylation status. Genes encoding other cyclin-dependent kinase inhibitors (CDKN2A/P16, CDKN2C/P18) were not methylated in DFL samples. Methylation of the genes of interest was not detected in DNAs from D-RLH, except for DAPK1, and the difference in the extent of methylation between NDU and D-RLH was statistically significant (P = 0.013). Our results suggest that D-RLH serves as a reservoir for the development of DFL and that methylation of CDKN2B/P15 plays an important role in this process.

十二指肠型滤泡淋巴瘤(DFL)是滤泡淋巴瘤(FL)的一种罕见类型,临床症状不明显,与结节性滤泡淋巴瘤(NFL)相比,其组织学分级较低。我们之前的报告显示,DFL 在临床和生物学方面与 NFL 和粘膜相关淋巴组织(MALT)淋巴瘤具有相同的特征,这表明其发病机制可能涉及抗原刺激。与 NFL 相比,DFL 的基因组甲基化状况仍具有挑战性。在这里,我们测定了 DFL(12 例)、NFL(10 例)、十二指肠反应性淋巴细胞增生症(D-RLH)(7 例)、结节反应性淋巴细胞增生症(N-RLH)(5 例)患者 DNA 的甲基化图谱、在对 MALT 淋巴瘤样本(CDKN2B/P15、CDKN2A/P16、CDKN2C/P18、MGMT、hMLH-1、TP73、DAPK、HCAD)进行甲基化特异性 PCR 检测时,对正常人(NDU)的十二指肠样本(n = 5)进行了甲基化特异性 PCR 检测。在 DFL(9/12;75%)、NFL(9/10;90%)和 D-RLH (5/7;71%)中,DAPK1 经常发生甲基化。CDKN2B/P15 序列在六个 DFL 样本中被甲基化,仅在一个 NFL 样本中被甲基化。免疫组化分析表明,p15的表达与甲基化状态成反比。在 DFL 样本中,编码其他细胞周期蛋白依赖性激酶抑制剂的基因(CDKN2A/P16、CDKN2C/P18)未发生甲基化。除 DAPK1 外,在 D-RLH 的 DNA 中未检测到相关基因的甲基化,NDU 和 D-RLH 之间的甲基化程度差异具有统计学意义(P = 0.013)。我们的研究结果表明,D-RLH 是 DFL 发展的储库,CDKN2B/P15 的甲基化在这一过程中起着重要作用。
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引用次数: 0
T-cell receptor gamma gene rearrangement analysis of classic Hodgkin lymphoma using a BIOMED-2 assay: a paraffin-embedded tissue analysis of one hundred cases. 使用 BIOMED-2 检测法对典型霍奇金淋巴瘤进行 T 细胞受体 gamma 基因重排分析:对 100 例石蜡包埋组织的分析。
IF 0.9 Q4 HEMATOLOGY Pub Date : 2024-01-01 DOI: 10.3960/jslrt.24027
Katsuyoshi Takata, Tomoko Miyata-Takata, Asami Nishikori, Tomoka Haratake, Yasuharu Sato

In the new WHO classifications of haematolymphoid tumours (WHO-HAEM5), classic Hodgkin lymphoma (cHL) is categorized into B-cell lymphoid proliferations and lymphomas. Although the majority of Hodgkin Reed-Sternberg (HRS) cells are of germinal center B-cell origin with some defects of B-cell transcription factors, they rarely express T-cell antigens or cytotoxic molecules. Clonality analyses on cHL samples using BIOMED-2 have been reported by several groups; however, those studies were only focused on Ig regions, including IgH, Ig-kappa, and Ig-lambda, and TCR-γ clonality analysis of cHL has not yet been explored. Here, we investigated TCR-γ gene rearrangement for one hundred cases using a PCR-based method. Four of one hundred (4%) cases showed TCR-γ clonal peaks. Of these, three were at an advanced stage and one patient died of the disease. To clarify whether HRS cells showed T-cell clonality or not, we performed PCR analysis using DNAs of microdissected HRS cells. Three samples showed identical clonal peaks with bulk specimens. Our results indicate that cHL is a heterogeneous disease of mainly B-cell and rarely T-cell origin with a special phenotype. Further molecular studies are warranted.

在世界卫生组织新的血液淋巴肿瘤分类(WHO-HAEM5)中,典型霍奇金淋巴瘤(cHL)被分为B细胞淋巴增生和淋巴瘤。虽然大多数霍奇金里德-斯特恩伯格(HRS)细胞起源于生殖中心B细胞,存在一些B细胞转录因子缺陷,但它们很少表达T细胞抗原或细胞毒性分子。已有多个研究小组报道了使用 BIOMED-2 对 cHL 样本进行克隆性分析,但这些研究只关注 Ig 区域,包括 IgH、Ig-kappa 和 Ig-lambda,而对 cHL 的 TCR-γ 克隆性分析尚未进行探讨。在此,我们采用基于 PCR 的方法调查了 100 例病例的 TCR-γ 基因重排情况。100 例病例中有 4 例(4%)出现了 TCR-γ 克隆峰。其中三例处于晚期,一例患者死于该病。为了明确HRS细胞是否具有T细胞克隆性,我们使用微切片HRS细胞的DNA进行了PCR分析。三个样本显示出与大块样本相同的克隆峰。我们的研究结果表明,cHL是一种异质性疾病,主要来源于B细胞,很少来源于T细胞,具有特殊的表型。有必要开展进一步的分子研究。
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引用次数: 0
Early failure is still a poor prognostic factor in patients with relapsed or refractory large B-cell lymphoma in the era of CAR T-cell therapy. 在 CAR T 细胞疗法时代,早期失败仍然是复发或难治性大 B 细胞淋巴瘤患者的一个不良预后因素。
IF 0.9 Q4 HEMATOLOGY Pub Date : 2024-01-01 DOI: 10.3960/jslrt.24009
Yu Yagi, Yusuke Kanemasa, Yuki Sasaki, Sotaro Goto, Yasuhiko Yamamura, Yusuke Masuda, Kumiko Fujita, Kento Ishimine, Yudai Hayashi, Mano Mino, An Ohigashi, Yuka Morita, Taichi Tamura, Shohei Nakamura, Toshihiro Okuya, Shinichiro Matsuda, Takuya Shimizuguchi, Naoki Shingai, Takashi Toya, Hiroaki Shimizu, Yuho Najima, Takeshi Kobayashi, Kyoko Haraguchi, Noriko Doki, Yoshiki Okuyama, Tatsu Shimoyama

Patients with refractory or relapsed (R/R) large B-cell lymphoma (LBCL) refractory to first-line chemotherapy or with early relapse have poor outcomes. While chimeric antigen receptor (CAR) T-cell therapy has impressive efficacy after two or more lines of chemotherapy, it's still uncertain if these outcomes remain consistent in the context of third-line CAR T-cell therapy. We conducted a retrospective study of 107 R/R LBCL patients. Patients with relapse 12 months or more after their first-line chemoimmunotherapy (late failure: n = 25) had significantly longer overall survival (OS) than patients with refractory disease or relapse within 12 months (early failure: n = 82) (median OS: not achieved vs. 18.4 months; P < 0.001). Among patients who proceeded to autologous hematopoietic stem-cell transplantation (auto-HSCT), those with late failure had significantly longer event-free survival (EFS) than those with early failure (median EFS: 26.9 vs. 3.1 months; P = 0.012). However, no significant difference in EFS was detected among patients who underwent CAR T-cell therapy (median EFS: not reached vs. 11.8; P = 0.091). Cox regression with restricted cubic spline demonstrated that timing of relapse had significant impact on EFS in patients with auto-HSCT but not in patients with CAR T-cell therapy. Of patients who were scheduled for CAR T-cell therapy, those with late failure were significantly more likely to receive CAR T-cell therapy than those with early failure (90% vs. 57%; P = 0.008). In conclusion, patients with early failure still experienced poor outcomes after the approval of third-line CAR T-cell therapy.

一线化疗难治或复发(R/R)的大 B 细胞淋巴瘤(LBCL)患者疗效不佳。虽然嵌合抗原受体(CAR)T细胞疗法在经过两线或更多线化疗后疗效显著,但三线CAR T细胞疗法的疗效是否一致仍不确定。我们对107例R/R LBCL患者进行了回顾性研究。一线化疗免疫治疗12个月或更长时间后复发的患者(晚期失败:n = 25)的总生存期(OS)明显长于难治性疾病或12个月内复发的患者(早期失败:n = 82)(中位OS:未达到vs 18.4个月;P < 0.001)。在进行自体造血干细胞移植(auto-HSCT)的患者中,晚期失败者的无事件生存期(EFS)明显长于早期失败者(中位EFS:26.9个月 vs. 3.1个月;P = 0.012)。然而,接受 CAR T 细胞治疗的患者的无事件生存期没有明显差异(中位无事件生存期:未达到 vs. 11.8;P = 0.091)。使用限制性立方样条曲线的 Cox 回归表明,复发时间对接受自体 HSCT 治疗的患者的 EFS 有显著影响,但对接受 CAR T 细胞治疗的患者没有影响。在计划接受CAR T细胞治疗的患者中,晚期失败患者接受CAR T细胞治疗的几率明显高于早期失败患者(90% vs. 57%; P = 0.008)。总之,三线CAR T细胞疗法获批后,早期失败患者的预后仍然不佳。
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引用次数: 0
C/EBP homogenous protein-induced Apoptosis in Endoplasmic Reticulum stress has been implicated in Kikuchi-Fujimoto Disease. C/EBP同源蛋白在内质网应激中诱导的细胞凋亡与菊池藤本病有关。
IF 0.9 Q4 HEMATOLOGY Pub Date : 2023-12-26 Epub Date: 2023-10-28 DOI: 10.3960/jslrt.23034
Shigeyuki Asano, Kazuki Yamazaki, Kikuo Mori, Yuko Hashimoto, Satoshi Kawana, Hiroko Sato, Hiroyuki Naito, Koji Shikano, Yoichiro Sogame, Makoto Kashimura
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引用次数: 0
期刊
Journal of Clinical and Experimental Hematopathology
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