Hematology最新文献_第10页

Quality assessment of the preparation and storage of leukocyte-depleted pooled platelet concentrates. 白细胞去除了的集合血小板浓缩物的制备和储存质量评估。

IF 1.9 4区医学

Hematology Pub Date : 2024-12-01 Epub Date: 2024-01-09 DOI: 10.1080/16078454.2023.2293492

Feng Chen, Xiaoqing Dai, Azhong Li, Yinhong Zheng, Wei Hu

{"title":"Quality assessment of the preparation and storage of leukocyte-depleted pooled platelet concentrates.","authors":"Feng Chen, Xiaoqing Dai, Azhong Li, Yinhong Zheng, Wei Hu","doi":"10.1080/16078454.2023.2293492","DOIUrl":"https://doi.org/10.1080/16078454.2023.2293492","url":null,"abstract":"Objective: To explore the feasibility of using a disposable platelet storage bag containing a leukocyte filter to prepare leukocyte-depleted pooled platelet concentrates with the buffy coat method.Methods: 150 bags of whole blood samples (400 mL/bag) were stored overnight at 22 ± 2°C, and buffy coats were separated on Day 2, then 5 units of ABO homotypic buffy coat and 1 unit of plasma were pooled into a disposable platelet storage bag containing a leukocyte filter to prepare leukocyte-depleted pooled platelet concentrates and stored in a Platelet Agitator. On Day 2, 4, 5 and 7 after the collection of whole blood, platelet content, pH value, pO2, pCO2, glucose (GLU), ATP, and other quality indicators were measured.Results: The quality indicators of leukocyte-depleted pooled platelet concentrates met the requirements for leukocyte-depleted aphaeresis platelets in the Chinese national standard Quality Requirements for Whole Blood and Blood Components (GB18469-2012). With the prolongation of storage time, MPV and PDW of platelets gradually increased, pH value, bicarbonate, and GLU gradually decreased, LA, LDH, and ATP gradually increased, pO2 slightly increased, pCO2 decreased, and HSR had no significant change. ESC decreased significantly on Day 7, CD62p decreased first and then increased, sP-selectin and GP V increased first and then decreased, but the results on Day 7 were higher than those on Day 2.Conclusion: The quality of leukocyte-depleted pooled platelet concentrates prepared by the buffy coat method using disposable platelet storage bags containing a leukocyte filter was comparable to that of leukocyte-depleted apheresis platelets, and could be used clinically.","PeriodicalId":13161,"journal":{"name":"Hematology","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139402588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Detection of α-thalassemia South-East Asian deletion based on a fully integrated digital polymerase chain reaction system DropXpert S6. 基于全集成数字聚合酶链反应系统 DropXpert S6 检测α-地中海贫血症东南亚缺失。

IF 2 4区医学

Hematology Pub Date : 2024-12-01 Epub Date: 2024-06-12 DOI: 10.1080/16078454.2024.2365596

Youqiong Li, Junwei Ye, Liang Liang, Xiao Tan, Lihong Zheng, Ting Qin, Linfen Yu

{"title":"Detection of α-thalassemia South-East Asian deletion based on a fully integrated digital polymerase chain reaction system DropXpert S6.","authors":"Youqiong Li, Junwei Ye, Liang Liang, Xiao Tan, Lihong Zheng, Ting Qin, Linfen Yu","doi":"10.1080/16078454.2024.2365596","DOIUrl":"10.1080/16078454.2024.2365596","url":null,"abstract":"Objectives: This study aimed to establish a droplet digital polymerase chain reaction (ddPCR) assay for South-East Asian (SEA) deletion based on a fully integrated digital PCR system DropXpert S6.Methods: A total of 151 whole blood samples, 10 chorionic villus samples, and 17 amniotic fluid samples were collected, including 106 SEA heterozygotes, 43 normal individuals, 10 Hb Bart's hydrops details, and 19 SEA deletions combined with other genotypes.Genotypes of these samples were determined by the Gap-PCR method. We perform a series of optimizations of the ddPCR system to ensure the performance of the entire ddPCR reaction, such as droplet stability, fluorescence clustering, sensitivity, and accuracy.Results: Our assay exhibited 99.4% (177/178) accuracy compared with the Gap-PCR method, and the minimum detection limit of DNA was 0.1 ng/μL.Both targets have reliable linearity, R2 = 0.9999 for the α-thalassemia SEA deletion allele and R2 = 1 for the wild-type allele. The coefficient of variation for α-thalassemia SEA deletion allele detection at 2 and 10 ng/μL concentrations was 5.42% and 1.91%, respectively. In contrast, the coefficient of variation for wild-type allele detection was 4.06% and 1.83%, demonstrating its high quantitative accuracy. In addition, the DropXpert S6 PCR system showed some advantages over other ddPCR instruments, such as reducing testing costs, simplifying and automating the workflow.Conclusions: The DropXpert S6 PCR system provided a highly accurate diagnosis for α-thalassemia SEA deletion and can be used to detect α-thalassemia as an alternative method.","PeriodicalId":13161,"journal":{"name":"Hematology","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141305846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Genotype and phenotype analysis of α-thalassemia fusion gene in southern China. 华南地区α地中海贫血融合基因的基因型和表型分析。

IF 2 4区医学

Hematology Pub Date : 2024-12-01 Epub Date: 2024-09-12 DOI: 10.1080/16078454.2024.2399361

Yi-Yuan Ge, Yan-Quan Lai, Ai-Ping Ju, Lie-Jun Li, Min Lu, Long-Xu Xie, Min Huang, Li-Ye Yang

{"title":"Genotype and phenotype analysis of α-thalassemia fusion gene in southern China.","authors":"Yi-Yuan Ge, Yan-Quan Lai, Ai-Ping Ju, Lie-Jun Li, Min Lu, Long-Xu Xie, Min Huang, Li-Ye Yang","doi":"10.1080/16078454.2024.2399361","DOIUrl":"https://doi.org/10.1080/16078454.2024.2399361","url":null,"abstract":"Objective: The α-globin fusion gene between the HBA2 and HBAP1 genes, is clinically important in thalassemia screening because this fusion gene can cause severe hemoglobin (Hb) H disease when combined with α0 -thalassemia (α0 -thal). In this study, we evaluate the red blood cell parameters of α-thalassemia fusion gene in southern China.Method: Study samples suspected of α-thalassemia fusion gene were collected and confirmed by PCR-sequencing from one medical lab center in southern China. Their genotypes and phenotypes were analyzed.Results: A total of 266 cases of α-thalassemia fusion gene were confirmed in our lab from 2017 to 2023, most of them were from Hainan province (169 cases) and Huadu district of Guangzhou (21 cases), the nationality of 143 cases from Hainan was identified, with 71.3% (102/143) being from the Li minority. The Hb, MCV, MCH for αα/(αα)fusion in adult males were 143.5±11.83g/L, 81.51±4.39 fl, and 26.26±1.29 pg, respectively; and in females, they were 126.69±12.89 g/L, 80.10±4.05 fl, 25.8±2.04 pg, respectively. All 12 cases (αα) Fusion/ --SEA showed anemia with decreased Hb, MCV and MCH.Conclusion: The carriers of α-globin fusion gene heterozygotes are clinically silent and exhibit an α+ phenotype. Individuals with (αα)Fusion/--SEA show apparent anemia. This α-globin fusion gene is relatively common in southern China, specifically among the Li minority of Hainan province. Therefore, it should be taken into account for genetic counseling purposes.","PeriodicalId":13161,"journal":{"name":"Hematology","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Hb SKMC and an unprecedented γδβ-thalassemia: first report from Iraq. 血红蛋白 SKMC 和前所未有的 γδβ 地中海贫血症：伊拉克的首次报告。

IF 2 4区医学

Hematology Pub Date : 2024-12-01 Epub Date: 2024-09-09 DOI: 10.1080/16078454.2024.2399356

Rawand P Shamoon, Amir Charkaneh, Elena Di Pierro, Milena Irrera, Cristina Curcio, Ahmed Yassin, Rozhgar A Khailany

{"title":"Hb SKMC and an unprecedented γδβ-thalassemia: first report from Iraq.","authors":"Rawand P Shamoon, Amir Charkaneh, Elena Di Pierro, Milena Irrera, Cristina Curcio, Ahmed Yassin, Rozhgar A Khailany","doi":"10.1080/16078454.2024.2399356","DOIUrl":"10.1080/16078454.2024.2399356","url":null,"abstract":"Background: Thalassemias are genetic disorders of globin chain synthesis. In Iraq, β-thalassemia is more prevalent than α-thalassemia. This study identifies two unpredicted globin gene mutations, a rare α-globin gene mutation (Hb SKMC) and a novel γδβ-thalassemia deletion.Methods: Over 2 years, the Genetics unit at PAR hospital in Erbil, northern Iraq processed 137 β-thalassemia and 97 α-thalassemia genetic testing requests. Three symptomatic thalassemia cases with unreported genotypes were identified. Proband-1α and proband-2α had Hb H disease, while proband-1β had severe transfusion-dependent β-thalassemia (TDT). Molecular studies included multiplex PCR, reverse hybridization, multiplex ligation-dependent probe amplification (MLPA), and globin gene sequencing.Results: The α-thalassemia probands exhibited moderate microcytic hypochromic anemia with irregular transfusions and splenomegaly. Hb H disease was confirmed by positive Hb H tests and high-performance liquid chromatography (HPLC). Molecular analysis revealed heterozygous -MED deletion in proband-1α and α2Poly-A2 mutation in proband-2α. Sequencing identified the Hb SKMC (HBA1:c.283_300+3dup) mutation in both probands. The β-thalassemia proband showed anemia and regular transfusions. Molecular studies detected the IVS1.110 G>A mutation and a novel γδβ-thalassemia deletion in compound heterozygous form. The maternal sample showed the IVS1.110 G>A mutation, and MLPA confirmed the γδβ-thalassemia deletion in the paternal sample.Conclusion: These findings highlight the genetic diversity of thalassemias in the region and emphasize the importance of advanced molecular diagnostics in detecting rare mutations.","PeriodicalId":13161,"journal":{"name":"Hematology","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Causal relationships between gut microbiome and aplastic anemia: a Mendelian randomization analysis. 肠道微生物群与再生障碍性贫血之间的因果关系：孟德尔随机分析。

IF 2 4区医学

Hematology Pub Date : 2024-12-01 Epub Date: 2024-09-06 DOI: 10.1080/16078454.2024.2399421

Juan Liu, Xin Wang, Liping Huang, Xinlu Lin, Wei Yin, Mingliang Chen

{"title":"Causal relationships between gut microbiome and aplastic anemia: a Mendelian randomization analysis.","authors":"Juan Liu, Xin Wang, Liping Huang, Xinlu Lin, Wei Yin, Mingliang Chen","doi":"10.1080/16078454.2024.2399421","DOIUrl":"https://doi.org/10.1080/16078454.2024.2399421","url":null,"abstract":"Background: Previous observational studies have hinted at a potential correlation between aplastic anemia (AA) and the gut microbiome. However, the precise nature of this bidirectional causal relationship remains uncertain.Methods: We conducted a bidirectional two-sample Mendelian randomization (MR) study to investigate the potential causal link between the gut microbiome and AA. Statistical analysis of the gut microbiome was based on data from an extensive meta-analysis (genome-wide association study) conducted by the MiBioGen Alliance, involving 18,340 samples. Summary statistical data for AA were obtained from the Integrative Epidemiology Unit database. Single -nucleotide polymorphisms (SNPs) were estimated and summarized using inverse variance weighted (IVW), MR Egger, and weighted median methods in the bidirectional MR analysis. Cochran's Q test, MR Egger intercept test, and sensitivity analysis were employed to assess SNP heterogeneity, horizontal pleiotropy, and stability.Results: The IVW analysis revealed a significant correlation between AA and 10 bacterial taxa. However, there is currently insufficient evidence to support a causal relationship between AA and the composition of gut microbiome.Conclusion: This study suggests a causal connection between the prevalence of specific gut microbiome and AA. Further investigation into the interaction between particular bacterial communities and AA could enhance efforts in prevention, monitoring, and treatment of the condition.","PeriodicalId":13161,"journal":{"name":"Hematology","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identification of a novel 145 kb deletion (Guigang deletion, -^Guigang) in the alpha-globin gene cluster from a Chinese newborn using third-generation sequencing. 利用第三代测序技术从一名中国新生儿体内鉴定出α-球蛋白基因簇中一个 145 kb 的新缺失（贵港缺失，-Guigang）。

IF 2 4区医学

Hematology Pub Date : 2024-12-01 Epub Date: 2024-10-09 DOI: 10.1080/16078454.2024.2412949

Jing Guo, Teng Li, Liang Liang, Wei Wei, Yan Li, Weilin Guo, Youqiong Li

{"title":"Identification of a novel 145 kb deletion (Guigang deletion, -Guigang) in the alpha-globin gene cluster from a Chinese newborn using third-generation sequencing.","authors":"Jing Guo, Teng Li, Liang Liang, Wei Wei, Yan Li, Weilin Guo, Youqiong Li","doi":"10.1080/16078454.2024.2412949","DOIUrl":"https://doi.org/10.1080/16078454.2024.2412949","url":null,"abstract":"Objective: To describe a novel α-thalassemiadeletion identified from a newborn by third-generation sequencing (TGS).Case report: The proband, a newborn subject to neonatal capillary electrophoresis (CE) screening, exhibited suspected α0-thalassemia carrier status (Hb Bart's 3.0%). Notably, both parents had negative results on thalassemia screening during pregnancy. Multiplex ligation-dependent probe amplification (MLPA) presented a deletion between probes 364nt and 472 nt that extended from the HBZ gene to the downstream region of the RGS11 gene. Subsequently, TGS determined the approximated break position of this deletion, indicating a length exceeding 145 kb (chr16:127,815-273,190 del 145376 bp). Sanger sequencing validated the upstream and downstream breakpoints of this deletion. Only maternal data were available for pedigree analysis, with the father's sample lacking. MLPA showed no deletion in the mother, suggesting possible paternal inheritance. The deletion was named Guigang deletion (--Guigang) after the proband's city of origin, Guigang.Conclusions: We reported a novel α-thalassemiadeletion and provided insights into the hematological phenotype and molecular analysis. These findings have implications for genetic counseling and prenatal diagnosis.","PeriodicalId":13161,"journal":{"name":"Hematology","volume":null,"pages":null},"PeriodicalIF":2.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Renal outcome in multiple myeloma patients with cast nephropathy: a retrospective analysis of potential predictive values on clinical and renal outcome. 患有铸型肾病的多发性骨髓瘤患者的肾脏预后：对临床和肾脏预后潜在预测值的回顾性分析。

IF 1.9 4区医学

Hematology Pub Date : 2024-12-01 Epub Date: 2024-02-08 DOI: 10.1080/16078454.2024.2311600

Lina Z Rüsing, Nicolas Kozakowski, Georg Jeryczynski, Lea Vospernik, Julia Riedl, Thomas Reiter, Heinz Gisslinger, Hermine Agis, Maria-Theresa Krauth

{"title":"Renal outcome in multiple myeloma patients with cast nephropathy: a retrospective analysis of potential predictive values on clinical and renal outcome.","authors":"Lina Z Rüsing, Nicolas Kozakowski, Georg Jeryczynski, Lea Vospernik, Julia Riedl, Thomas Reiter, Heinz Gisslinger, Hermine Agis, Maria-Theresa Krauth","doi":"10.1080/16078454.2024.2311600","DOIUrl":"10.1080/16078454.2024.2311600","url":null,"abstract":"Objective: Cast nephropathy (CN) is the leading cause of acute kidney injury (AKI) in multiple myeloma (MM). Since it is sparsely documented why some patients with CN do achieve a renal response while others do not, we describe a single-center cohort of patients with multiple myeloma and biopsy-confirmed CN to evaluate potential markers of renal response.Methods: The data was collected as a retrospective, single-center analysis of CN-patients treated at the Medical University Vienna between 01/01/2004 and 01/01/2022. Baseline parameters and clinical outcome was compared between renal responders and non-responders.Results: Among 28 patients with CN, n = 23 were assessed for renal response (14 responders; 9 non-responders). Renal responders were younger (median age: 61 years; 77 years, p = 0.039), showed higher overall survival (153months; 58months, p = 0.044) and achieved hematologic response (≥PR) to first-line therapy (p = 0.029), and complete hematologic response (CR) at any time (p = 0.025) significantly more often. Further, we could show that rapid initiation of anti-myeloma therapy after initial presentation correlated significantly with renal response (median 9 days; 27 days, p = 0.016). Analyses of kidney biopsy specimens revealed that patients with a high IF/TA score showed end stage renal disease (dialysis ≥ 3 months) significantly more often (p = <0.001).Discussion: In summary, our data suggests, that a rapid start with systemic hematologic treatment in patients with MM and CN is crucial and achieving an early hematologic response is important for renal recovery. Moreover, achieving a deep hematologic response and subsequent renal recovery improves clinical outcome as reflected by an overall survival benefit.","PeriodicalId":13161,"journal":{"name":"Hematology","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139702399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

TIM3 and CTLA4 immune checkpoint polymorphisms are associated with acute myeloid leukemia in Saudi Arabia. 沙特阿拉伯的 TIM3 和 CTLA4 免疫检查点多态性与急性髓性白血病有关。

IF 1.9 4区医学

Hematology Pub Date : 2024-12-01 Epub Date: 2024-03-27 DOI: 10.1080/16078454.2024.2329024

Mashael Alqahtani, Ali Aljuaimlani, Jameel Al-Tamimi, Suliman Alomar, Lamjed Mansour

{"title":"TIM3 and CTLA4 immune checkpoint polymorphisms are associated with acute myeloid leukemia in Saudi Arabia.","authors":"Mashael Alqahtani, Ali Aljuaimlani, Jameel Al-Tamimi, Suliman Alomar, Lamjed Mansour","doi":"10.1080/16078454.2024.2329024","DOIUrl":"10.1080/16078454.2024.2329024","url":null,"abstract":"Background: Immune checkpoints are receptors on the surface of T cells that function crucially in suppressing the immune response, and they are implicated in autoimmunity and cancer diseases.Aim: The present study aimed to investigate the relationship between functional single nucleotide polymorphisms (SNPs) of two immune checkpoint molecules, CTLA-4 and TIM-3, and acute myeloid leukemia (AML) in a Saudi population.Methods: Two SNPs in CTLA-4 (rs231775, A > G) and TIM-3 (rs10515746, A > C) were genotyped in 229 subjects, including 98 patients and 131 healthy controls, from the Saudi population using TaqMan assay methods. Differential expression of these two genes was performed using in silico analysis.Results: An association was found between polymorphisms in TIM-3 (OR: 6.01; 95% CI: 3.99-9.05, P < 0.0001) and the risk of AML. Inversely, the rs231775 SNP in the CTLA-4 gene was found to protect against AML in allelic, dominant, and additive models (P < 0.05). A significantly higher expression of TIM-3 in the blood of individuals with AML was observed.Conclusion: This is the first study focusing on single nucleotide polymorphisms (SNPs) for CTLA-4 and TIM-3 in acute myeloid leukemia patients in a Saudi community and could be a potential new prognostic factor for this disease.","PeriodicalId":13161,"journal":{"name":"Hematology","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140293402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Insights into the role of JAK2-I724T variant in myeloproliferative neoplasms from a unique cohort of New Zealand patients. 从独特的新西兰患者队列中洞察 JAK2-I724T 变体在骨髓增生性肿瘤中的作用。

IF 1.9 4区医学

Hematology Pub Date : 2024-12-01 Epub Date: 2024-01-10 DOI: 10.1080/16078454.2023.2297597

Christopher Puli'uvea, Tracey Immanuel, Taryn N Green, Peter Tsai, Peter R Shepherd, Maggie L Kalev-Zylinska

{"title":"Insights into the role of JAK2-I724T variant in myeloproliferative neoplasms from a unique cohort of New Zealand patients.","authors":"Christopher Puli'uvea, Tracey Immanuel, Taryn N Green, Peter Tsai, Peter R Shepherd, Maggie L Kalev-Zylinska","doi":"10.1080/16078454.2023.2297597","DOIUrl":"10.1080/16078454.2023.2297597","url":null,"abstract":"Objectives: This study aimed to compile bioinformatic and experimental information for JAK2 missense variants previously reported in myeloproliferative neoplasms (MPN) and determine if germline JAK2-I724T, recently found to be common in New Zealand Polynesians, associates with MPN.Methods: For all JAK2 variants found in the literature, gnomAD_exome allele frequencies were extracted and REVEL scores were calculated using the dbNSFP database. We investigated the prevalence of JAK2-I724T in a cohort of 111 New Zealand MPN patients using a TaqMan assay, examined its allelic co-occurrence with JAK2-V617F using Oxford Nanopore sequencing, and modelled the impact of I724T on JAK2 using I-Mutant and ChimeraX software.Results: Several non-V617F JAK2 variants previously reported in MPN had REVEL scores greater than 0.5, suggesting pathogenicity. JAK2-I724T (REVEL score 0.753) was more common in New Zealand Polynesian MPN patients (n = 2/27; 7.4%) than in other New Zealand patients (n = 0/84; 0%) but less common than expected for healthy Polynesians (n = 56/377; 14.9%). Patients carrying I724T (n = 2), one with polycythaemia vera and one with essential thrombocythaemia, had high-risk MPN. Both patients with JAK2-I724T were also positive for JAK2-V617F, found on the same allele as I724T, as well as separately. In silico modelling did not identify noticeable structural changes that would give JAK2-I724T a gain-of-function.Conclusion: Several non-canonical JAK2 variants with high REVEL scores have been reported in MPN, highlighting the need to further understand their relationship with disease. The JAK2-I724T variant does not drive MPN, but additional investigations are required to exclude any potential modulatory effect on the MPN phenotype.","PeriodicalId":13161,"journal":{"name":"Hematology","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139402587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Overexpression of PTPN21 promotes proliferation of EGF-stimulated acute lymphoblastic leukemia cells via the MAPK signaling pathways. 过表达 PTPN21 可通过 MAPK 信号通路促进 EGF 刺激的急性淋巴细胞白血病细胞的增殖。

IF 1.9 4区医学

Hematology Pub Date : 2024-12-01 Epub Date: 2024-05-24 DOI: 10.1080/16078454.2024.2356292

Ni Zhu, Jieping Wei, Li-Mengmeng Wang, He Huang, Haowen Xiao

{"title":"Overexpression of PTPN21 promotes proliferation of EGF-stimulated acute lymphoblastic leukemia cells via the MAPK signaling pathways.","authors":"Ni Zhu, Jieping Wei, Li-Mengmeng Wang, He Huang, Haowen Xiao","doi":"10.1080/16078454.2024.2356292","DOIUrl":"10.1080/16078454.2024.2356292","url":null,"abstract":"Objectives: This study aims to investigate the role of excessive Protein Tyrosine Phosphatase Non-Receptor Type 21 (PTPN21) in the proliferation of Acute Lymphoblastic Leukemia (ALL) cells with EGF stimulation.Methods: PTPN21 was overexpressed in ALL cell lines by lentiviral transfection. Apoptosis was assayed by Annexin V/7-AAD staining. The proliferation and cell cycle of EGF-treated ALL cells were assessed by MTT and Ki-67/7-AAD staining respectively. The phosphorylation of Src tyrosine kinase and mediators of distinct MAPK pathways were assessed by Western blot.Results: Overexpression of PTPN21 had minimal effect on the apoptosis of ALL cells, but significantly promoted the proliferation and cell cycle progression of ALL cells stimulated with EGF. The activity of Src tyrosine kinase and the MAPK pathways was elevated. Inhibition of MAPK pathways by specific inhibitors mitigated this pro-proliferative effect of excessive PTPN21 on EGF-stimulated ALL cells.Conclusion: PTPN21 may facilitate ALL progression by promoting cell proliferation via the Src/MAPK signaling pathways.","PeriodicalId":13161,"journal":{"name":"Hematology","volume":null,"pages":null},"PeriodicalIF":1.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141086035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0