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HES-1 and CEBPA mRNA in Chronic and Late Phase (accelerated and blast crisis) of Chronic Myeloid Leukemia (CML) Patients HES-1和CEBPA mRNA在慢性粒细胞白血病(CML)患者慢性期和晚期(加速期和急危期)的表达
Pub Date : 2017-02-13 DOI: 10.4172/2329-6917.1000225
Selvi Rahmawati, S. Fatmawati, Stefanus Purwanto, Eugeu Yasmin, Susan Simanjaya, S. Hutajulu, D. K. Paramita
Chronic Myeloid Leukemia (CML) is a myeloproliferative disorder of hematopoietic , characterized by Philadelphia chromosome containing BCR-ABL fusion gene. The gene encodes protein with constitutive tyrosine kinase activity result in myeloid proliferation and leads to form an early phase of CML called chronic phase. Unsuccessful treatment will lead to progression of the disease into late phase (accelerated and blast crisis). The mechanisms involving disease progression are still poorly understood. It is assumed that additional genetic event involves in differentiation blocking of myeloid progenitor cells, such as Hes-1 overexpression and CEBPA down regulation. However, study on the expression of these genes in CML patient’s samples is still limited. This study aims to measure Hes-1 and CEBPA mRNA in chronic and late phase of CML patients. The peripheral blood mRNA level of Hes-1 was measured in CML patient’s sample with BCR-ABL positive both in chronic phase (n=61) and late phase (n=17) using qRT-PCR with GAPDH as internal control. Hes-1 mRNA was statistically higher (p value=0.0) in the chronic phase (mean ± SD=97.8 ± 236.6) compared to those in late phase (mean ± SD=8.5 ± 30.7). In addition, even though CEBPA expression in chronic and late phase were not statistically different (p value=0.1), those in chronic phase (mean ± SD=5.2 ± 16.0) were generally higher compared to those in late phase (mean ± SD=1.7 ± 2.4). Hes-1 expression upregulated in 70.5% of chronic phase patients and in 17.6% of late phase patients, whereas CEBPA expression down regulated in 42.6% of chronic phase patients and in 47.1% in late phase patients. High standard deviation, particularly in mRNA Hes-1 gene expression measurement of the chronic phase, indicated the presence of individual variations in the sample that might be influenced by other genetic factors. This study found that Hes-1 mRNA is significantly higher in peripheral blood of chronic phase than blast crisis CML, whereas CEBPA mRNA is not different.
慢性粒细胞白血病(CML)是一种骨髓增生性造血系统疾病,其特征是费城染色体含有BCR-ABL融合基因。该基因编码具有组成型酪氨酸激酶活性的蛋白质,导致骨髓增生,并导致形成CML的早期阶段,称为慢性期。治疗不成功将导致疾病进展到晚期(加速和爆发危机)。涉及疾病进展的机制仍知之甚少。据推测,额外的遗传事件涉及骨髓祖细胞的分化阻断,如Hes-1过表达和CEBPA下调。然而,对这些基因在慢性粒细胞白血病患者样本中表达的研究仍然有限。本研究旨在检测慢性粒细胞白血病(CML)患者慢性期和晚期的Hes-1和CEBPA mRNA。在慢性期(n=61)和晚期(n=17)BCR-ABL阳性的CML患者样本中,使用以GAPDH为内部对照的qRT-PCR测量Hes-1的外周血mRNA水平。Hes-1 mRNA在慢性期(平均值±SD=97.8±236.6)比晚期(平均值?SD=8.5±30.7)具有统计学意义(p值=0.0)。此外,尽管CEBPA在慢性期和晚期的表达没有统计学差异(p值=0.1),慢性期患者(平均值±SD=5.2±16.0)通常高于晚期患者(平均数±SD=1.7±2.4)。Hes-1在70.5%的慢性期患者和17.6%的晚期患者中表达上调,而CEBPA在42.6%的慢性期病人和47.1%的晚期病人中表达下调。高标准偏差,特别是在慢性期的mRNA Hes-1基因表达测量中,表明样本中存在可能受到其他遗传因素影响的个体变异。本研究发现,慢性期外周血中Hes-1 mRNA显著高于急性粒细胞白血病,而CEBPA mRNA没有差异。
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引用次数: 1
Chronic Myelogenous Leukemia: Approaches to Pharmacological Resistance 慢性骨髓性白血病:药物耐药性的途径
Pub Date : 2017-02-02 DOI: 10.4172/2329-6917.1000E120
C. Corrado
From 2000 some data relative to IM resistance were available. There are many mechanisms responsible of IM resistance, more often point mutations that cause the progression to blast crisis and death in few months. To circumvent them, more potent TKIs have been subsequently approved [3]. However, another problem arise: these compounds don’t work on all patients because of the different IMresistant mutants of BCR-ABL[4].
从2000年开始,有一些关于耐药的数据。有许多机制负责IM耐药性,更常见的是点突变,导致在几个月内爆发危机和死亡。为了规避它们,更有效的tki随后被批准。然而,另一个问题出现了:这些化合物并不是对所有患者都有效,因为BCR-ABL[4]有不同的耐药突变体。
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引用次数: 0
Rapid Onset of Acute Miliary Pulmonary Tuberculosis in a Child with AcuteLymphoblastic Leukemia 急性淋巴细胞白血病儿童急性军性肺结核的快速发病
Pub Date : 2017-01-20 DOI: 10.4172/2329-6917.1000224
C. Jia, Ruidong Zhang, Shunying Zhao, Yuanyuan Zhang, Ying Wu, Jia Fan, Huyong Zheng
Mycobacterium tuberculosis (TB) is not uncommon in immunocompromised patients. TB is often neglected because of its atypical manifestation, especially in the early stages of disease. Although some leukemic patients are complicated with co-presentation of TB during their immunosuppressed stage, the advent of miliary pulmonary TB is seldom reported. Herein, we describe a case of active TB in a 6-year-old male with acute lymphoblastic leukemia during the late maintenance phase of therapy. He developed acute miliary pulmonary TB within two weeks after initial signs of lung presentation. The patient recovered in two months by anti-TB treatment of four co-administered therapies
结核分枝杆菌(TB)在免疫功能低下的患者中并不罕见。结核病由于其非典型表现,特别是在疾病的早期阶段,常常被忽视。虽然一些白血病患者在免疫抑制期合并结核,但军旅性肺结核的出现鲜有报道。在这里,我们描述了一例活动性结核在6岁的男性急性淋巴细胞白血病在治疗的后期维持阶段。他在最初的肺部症状出现后两周内发展为急性军用性肺结核。患者在接受了四种联合治疗的抗结核治疗后,在两个月内康复
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引用次数: 0
Primary Bone Burkitt’s like Lymphoma of the Skull Mimicking Meningioma-Case Report and Review of Literature 原发性骨伯基特样颅骨淋巴瘤模拟脑膜瘤1例报告及文献复习
Pub Date : 2017-01-01 DOI: 10.4172/2329-6917.1000241
Rita Nader, E. Saad, V. Najjar, Annoir Shayya, Y. Comair, H. Ghanem
Primary Bone Lymphoma of the skull is extremely rare and has a variable clinical course and prognosis. We are describing a case of a 26 year old woman who presented with a 2 year history of intermittent scalp swelling and skull pain. Brain MRI showed thickening of the bilateral frontal bones and band thickening of the underlying meninges suggestive of band meningiomatosis. Patient was presumably diagnosed with a meningioma based on radiological findings and underwent resection; however, pathology was consistent with a B-cell lymphoma with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma. A PET CT scan showed sacral bone hypermetabolic lesion which was biopsied and consistent with same lymphoma features. She received chemotherapy with Rituximab and Hyper-CVAD protocol (Table 1) and had a sustained ongoing complete remission 19 months after her initial diagnosis. Several cases of primary lymphoma of the skull or cranial vault have been described in the literature, but only one other case with the same pathology of Burkittlike lymphoma was found.
原发性颅骨骨淋巴瘤极为罕见,临床病程和预后不一。我们正在描述一个26岁女性的病例,她出现了2年的间歇性头皮肿胀和头骨疼痛史。脑MRI显示双侧额骨增厚,下脑膜带状增厚提示带状脑膜瘤病。根据影像学检查结果,患者可能被诊断为脑膜瘤,并接受了手术切除;病理表现为b细胞淋巴瘤,特征介于弥漫性大b细胞淋巴瘤和伯基特淋巴瘤之间。PET CT扫描显示骶骨高代谢性病变,活检显示与相同的淋巴瘤特征一致。她接受了利妥昔单抗和Hyper-CVAD方案的化疗(表1),并在初次诊断后19个月持续完全缓解。文献中已经报道了几例原发性颅骨或颅顶淋巴瘤,但只发现了一例具有相同病理的伯基特样淋巴瘤。
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引用次数: 0
Role of Allogeneic Stem Cell Transplant in Chronic Lymphocytic Leukemia and its Implications in Current Era 同种异体干细胞移植在慢性淋巴细胞白血病中的作用及其当代意义
Pub Date : 2017-01-01 DOI: 10.4172/2329-6917.1000E121
F. Socola
CLL is the most prevalent adult leukemia in the western countries with 18,960 new cases diagnosed in 2016 and estimated mortality of 25% per year [1]. It is an extremely heterogeneous disease with the clinical course varying from patients who never require therapy to a rapidly progressive and fatal malignancy in others. While most patients treated with fludarabine, cyclophosphamide and rituximab achieve 3-years OS of 87%, there is a high risk CLL group that has a dismal prognosis with a 4-years OS of less than 20% when they are treated with chemo immunotherapy [2,3]. High risk CLL is defined by presence of non-response or early relapse (within 12 months) after purine analogues, relapse within 24 months after having achieved a response with purine analogue-based combination therapy or autologous transplantation, and patients with p53 mutation or del(17p) requiring treatment. In 2007 the European Group for Bone Marrow Transplantation (EBMT) recommended that patient with high risk disease should be considered for allogeneic stem cell transplant [4].
CLL是西方国家最常见的成人白血病,2016年诊断出18960例新病例,估计死亡率为每年25%。它是一种异质性极强的疾病,其临床病程各不相同,从从不需要治疗的患者到迅速进展和致命的恶性肿瘤。虽然大多数接受氟达拉滨、环磷酰胺和利妥昔单抗治疗的患者3年生存率为87%,但有高风险的CLL患者在接受化疗免疫治疗时,预后不佳,4年生存率低于20%[2,3]。高风险CLL的定义是:在嘌呤类似物治疗后无反应或早期复发(12个月内),在基于嘌呤类似物的联合治疗或自体移植获得反应后24个月内复发,以及需要治疗的p53突变或del(17p)患者。2007年,欧洲骨髓移植组织(EBMT)建议高风险患者应考虑接受同种异体干细胞移植。
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引用次数: 0
Chronic Lymphocytic Leukemia with Aberrant CD8 Expression and Atypical Morphology: A Case Report and Review 慢性淋巴细胞白血病伴CD8表达异常及非典型形态1例报告及复习
Pub Date : 2017-01-01 DOI: 10.4172/2329-6917.1000242
Bowen Li, D. Amato, Chen Wang
Chronic lymphocytic leukemia (CLL) is a mature B-cell neoplasm with characteristic immunophenotype. This report presents a rare case of CLL with co-expression of T-cell marker CD8. The molecular analysis confirmed clonal immunoglobulin genes and no clonal rearrangement for T-cell receptor β and γ genes. The cell morphology was atypical of CLL, with features resembling reactive T lymphocytes. The phenotypic and morphologic findings may represent a CLL variant.
慢性淋巴细胞白血病(CLL)是一种成熟的b细胞肿瘤,具有独特的免疫表型。本文报告一例罕见的伴有t细胞标志物CD8共表达的CLL。分子分析证实免疫球蛋白基因克隆,t细胞受体β和γ基因无克隆重排。细胞形态不典型CLL,具有类似反应性T淋巴细胞的特征。表型和形态学的发现可能代表一个CLL变异。
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引用次数: 0
Clinical Significance of Wt1 mRNA Levels in Japanese Acute Lymphoblastic Leukemia Patients 日本急性淋巴细胞白血病患者Wt1 mRNA水平的临床意义
Pub Date : 2017-01-01 DOI: 10.4172/2329-6917.1000243
Y. Hashii, Y. Kosaka, Kenichiro Watanabe, Koji Kato, M. Imaizumi, T. Kaneko, S. Sunami, A. Watanabe, H. Hiramatsu, Yuhki Koga, M. Hirayama, T. Nakao, T. Hata, N. Uchida, K. Ishiyama, K. Mitani, M. Hidaka, K. Kitamura, Hiroko Tsunemine, Y. Ueda, A. Mugitani, K. Usuki, Y. Kanda, Y. Miyazaki, K. Imai, T. Naoe, K. Koh, H. Sugiyama, K. Horibe
This study enrolled 49 patients with de novo childhood acute lymphoblastic leukemia (ALL) and 19 adult patients with ALL. WT1 mRNA showed high positive expression rates of 90% or more in ALL patients, and fusion gene transcripts were detected in 22.4% of childhood ALL cases prior to treatment. During follow-up at 4-6 months, WT1 mRNA levels in childhood ALL cases were observed to be lower in patients undergoing hematological remission after treatment when compared to the initial stages. We also assessed hematological remission via ROC analysis. The upper cut-off values were calculated to be 220 and 1,820 copies/μg RNA in the peripheral blood (PB) and bone marrow (BM) samples, respectively. Since 50 copies/μg RNA was determined to be both, the limit of detection (LOD) and minimal residual disease (MRD) threshold, WT1 mRNA regions below the upper cut-off values indicated remission depth. The detection of high WT1 mRNA levels, even in patients without fusion gene transcripts, reflected the treatment effects and remission depth, demonstrating its capacity to be a useful MRD monitoring marker in ALL.
本研究招募了49例新生儿童急性淋巴细胞白血病(ALL)患者和19例成年ALL患者。WT1 mRNA在ALL患者中呈90%以上的高阳性表达率,治疗前在22.4%的儿童ALL病例中检测到融合基因转录物。在随访4-6个月期间,观察到治疗后血液学缓解的儿童ALL患者的WT1 mRNA水平低于初始阶段。我们还通过ROC分析评估血液学缓解。计算出外周血(PB)和骨髓(BM)样品的上临界值分别为220和1820拷贝/μg RNA。由于50拷贝/μg RNA被确定为检测限(LOD)和最小残留病(MRD)阈值,WT1 mRNA区域低于上限临界值表明缓解深度。即使在没有融合基因转录本的患者中检测到高WT1 mRNA水平,也反映了治疗效果和缓解深度,表明其能够成为ALL中有用的MRD监测标志物。
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引用次数: 0
Changing the Way We Approach Rehabilitation in Bone Marrow Transplantation 改变我们对待骨髓移植康复的方式
Pub Date : 2017-01-01 DOI: 10.4172/2329-6917.1000236
S. Abo, C. Granger
Allogeneic bone marrow transplantation (alloBMT) is a highly intensive form of treatment for people with haematological cancer. Given its intensity and potential short and long term complications, there are significant risks of physical and psychological morbidity following treatment [1]. Several studies have identified that the side effects of an alloBMT can be long term and include physical impairments such as muscle weakness and reduced endurance; persistent symptoms such as fatigue; and poor health-related quality of life (HRQoL) [2,3]. Whilst the side effects observed in allogeneic and autologous BMT are similar, those experienced following an alloBMT are more numerous and severe due to prolonged hospital length of stay and greater risk of debilitating long-term complications such as graftversus-host-disease [1,4]. The survival rate for patients treated with alloBMT is increasing [5] and therefore as this chronic disease population increases in size, there is awareness of the need to focus on prevention of long-term morbidity and addressing patient survivorship needs.
同种异体骨髓移植(Allogeneic bone marrow transplantation, alloBMT)是血液学癌症患者的一种高度强化的治疗形式。鉴于其强度和潜在的短期和长期并发症,治疗bbb后存在显著的生理和心理发病率风险。一些研究已经确定同种异体bmt的副作用可能是长期的,包括身体损伤,如肌肉无力和耐力降低;持续性症状,如疲劳;健康相关生活质量(HRQoL)较差[2,3]。虽然同种异体和自体骨髓移植中观察到的副作用相似,但同种异体骨髓移植后的副作用更多、更严重,因为住院时间更长,出现长期并发症(如移植物抗宿主病)的风险更大[1,4]。接受同种异体bmt治疗的患者的生存率正在增加,因此,随着这种慢性疾病人群规模的增加,人们意识到需要关注预防长期发病率和解决患者生存需求。
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引用次数: 1
Azacitidine Related Pyoderma Gangrenosum 阿扎胞苷相关性坏疽性脓皮病
Pub Date : 2017-01-01 DOI: 10.4172/2329-6917.1000237
Tamim Alsuliman, K. Debbache, M. Terrom, E. Maillot, Kaiss Lassouedand Bachra Choufi
Tamim Alsuliman1,2, Karima Debbache1, Maelle Terrom1, Elisabeth Maillot2, Kaiss Lassoued1 and Bachra Choufi1* 1Department of Hematology, Boulogne-sur-Mer Hospital Center, Boulogne-sur-Mer, France 2Department of Hematology, Center Hospitalier Régionale Universitaire, Lille, France 3Cabinet of Anatomy and Pathological Cytology, Saint Omer Cedex *Corresponding author: Bachra Choufi, Department of Hematology, Boulogne-sur-Mer Hospital Center, Boulogne-sur-Mer, France, Tel: 861033520; E-mail: b.choufi@gmail.com
Tamim alsuliman1,2, Karima Debbache1, Maelle Terrom1, Elisabeth Maillot2, Kaiss Lassoued1和Bachra Choufi1* 1法国滨海布洛涅滨海医院中心血液科2法国利耶尔 大学医院中心血液科3圣奥梅尔Cedex解剖与病理细胞学柜*通讯作者:Bachra Choufi,法国滨海布洛涅滨海医院中心血液科,电话:861033520;电子邮件:b.choufi@gmail.com
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引用次数: 0
Myelodysplastic Syndromes and Other Precursor Myeloid Neoplasms in the Era of Genomic Medicine (Mini Review) 基因组医学时代的骨髓增生异常综合征和其他前体髓系肿瘤(综述)
Pub Date : 2016-12-25 DOI: 10.4172/2329-6917.1000223
Ling Zhang, Lynh Nguyen
Myeloid neoplasm are derived from precursor cells of myeloid lineage and are composed of a broad spectrum of hematopoietic malignancies. The nature of the myeloid precursors is largely under-investigated until the recent application of next generation sequencing (NGS) technology for genome-wide analysis of myeloid neoplasms. It is important to define precursor myeloid neoplasms mediated by molecular signatures including driver gene mutations essential in disease initiation as well as acquired genetic alterations that play a role in disease progression. In addition to myelodysplastic syndrome with a high risk of leukemic transformation, there are newly proposed early precursor disorders with the potential to evolve into myeloid neoplasms [e.g., clonal hematopoiesis of indeterminate potential (CHIP), and clonal cytopenias of undetermined significance (CCUS)]. Furthermore, certain predisposing germline mutations (e.g. CEBPA, DDX41, RUNX1, ETV6 and GATA) have been recognized with predisposition to develop into myeloid neoplasms. This review paper aims to provide a brief summary of novel concepts of early precursor lesions that could lead to myeloid neoplasms, potential molecular prognostic indicators for MDS, and updated sub-classification of myelodysplastic syndromes according to the 2016 revision of World Health Organization (WHO).
髓系肿瘤来源于髓系的前体细胞,是一种广谱的造血恶性肿瘤。在下一代测序(NGS)技术用于髓系肿瘤全基因组分析之前,髓系前体的性质在很大程度上尚未得到研究。定义由分子特征介导的前体髓系肿瘤是很重要的,这些分子特征包括在疾病启动中必不可少的驱动基因突变以及在疾病进展中起作用的获得性遗传改变。除了具有白血病转化高风险的骨髓增生异常综合征外,还有一些新提出的早期前体疾病有可能演变为髓系肿瘤[例如,不确定潜力的克隆造血(CHIP)和不确定意义的克隆性细胞减少(CCUS)]。此外,某些易感种系突变(如CEBPA、DDX41、RUNX1、ETV6和GATA)已被认为具有发展为髓系肿瘤的易感性。本文旨在简要总结可能导致髓系肿瘤的早期前体病变的新概念,MDS的潜在分子预后指标,以及根据2016年世界卫生组织(WHO)修订的骨髓增生异常综合征的最新亚分类。
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引用次数: 0
期刊
Journal of leukemia (Los Angeles, Calif.)
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