Mei Yang, Pinpin Liu, Xiaohong Li, Lin Zhong, Ping Qiao
{"title":"Intracellular Brucella melitensis in the cerebrospinal fluid and peripheral blood","authors":"Mei Yang, Pinpin Liu, Xiaohong Li, Lin Zhong, Ping Qiao","doi":"10.1111/ijlh.14334","DOIUrl":"https://doi.org/10.1111/ijlh.14334","url":null,"abstract":"","PeriodicalId":14120,"journal":{"name":"International Journal of Laboratory Hematology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141528836","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}
The manuscript discusses the historical evolution of observing blood cell morphology under an optical microscope, from the earliest microscopes in the 17th century to the modern digital era, highlighting key advancements and contributions in the field. Blood has historically held symbolic importance in various cultures, with early medical observations dating back to Hippocrates and Galeno. The discovery of cells and subsequent advancements in microscopy by scientists like Hooke and van Leeuwenhoek paved the way for understanding blood cell morphology. Influential figures such as Hewson, Donné, and Ehrlich followed. Diagnostic cytology evolved from manual cell counting to the development of automated hematological systems. Automated complete blood counting came to support microscopic examination in diagnosing hematological disorders. Morphology is crucial in predicting disease outcomes and guiding treatment decisions, particularly hematological neoplasms. The introduction of flow cytometry and its integration with traditional morphological analysis and the new cytogenetic and molecular techniques revolutionized the classification and prognostication of hematologic disorders. Digital microscopy has emerged as a powerful tool in recent years, offering rapid acquisition and sharing of blood cell images. Integrating Artificial Intelligence with digital microscopy has further enhanced morphological analysis, improving diagnostic efficiency. We also discuss the prospects of AI in pre-classifying blood cells in bone marrow aspirate samples, potentially revolutionizing diagnostic pathways for hematologic diseases. Overall, the manuscript provides a comprehensive overview of the historical development, clinical significance and technological advancements in observing blood cell morphology, underscoring its continued relevance in modern hematology practice.
{"title":"Hematological cytomorphology: Where we are","authors":"G. Zini","doi":"10.1111/ijlh.14330","DOIUrl":"10.1111/ijlh.14330","url":null,"abstract":"<p>The manuscript discusses the historical evolution of observing blood cell morphology under an optical microscope, from the earliest microscopes in the 17th century to the modern digital era, highlighting key advancements and contributions in the field. Blood has historically held symbolic importance in various cultures, with early medical observations dating back to Hippocrates and Galeno. The discovery of cells and subsequent advancements in microscopy by scientists like Hooke and van Leeuwenhoek paved the way for understanding blood cell morphology. Influential figures such as Hewson, Donné, and Ehrlich followed. Diagnostic cytology evolved from manual cell counting to the development of automated hematological systems. Automated complete blood counting came to support microscopic examination in diagnosing hematological disorders. Morphology is crucial in predicting disease outcomes and guiding treatment decisions, particularly hematological neoplasms. The introduction of flow cytometry and its integration with traditional morphological analysis and the new cytogenetic and molecular techniques revolutionized the classification and prognostication of hematologic disorders. Digital microscopy has emerged as a powerful tool in recent years, offering rapid acquisition and sharing of blood cell images. Integrating Artificial Intelligence with digital microscopy has further enhanced morphological analysis, improving diagnostic efficiency. We also discuss the prospects of AI in pre-classifying blood cells in bone marrow aspirate samples, potentially revolutionizing diagnostic pathways for hematologic diseases. Overall, the manuscript provides a comprehensive overview of the historical development, clinical significance and technological advancements in observing blood cell morphology, underscoring its continued relevance in modern hematology practice.</p>","PeriodicalId":14120,"journal":{"name":"International Journal of Laboratory Hematology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ijlh.14330","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141428568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Koen Jacobs, Alena Moerman, Karl Vandepoele, Tim Van den Abeele, Katrien De Mulder, Eva Steel, Maxim Clauwaert, Henk Louagie
Introduction
Accurate quantification of the BCR::ABL1 fusion gene in whole blood is pivotal for the clinical management of chronic myeloid leukemia (CML) patients. The fusion protein encoded by BCR::ABL1 can vary in size, depending on the BCR and/or ABL1 gene breakpoint. The vast majority of CML patients have a p210 BCR::ABL1 fusion gene (M-BCR), which can be attributed to the presence of either e14a2 (b3a2) or e13a2 (b2a2) mRNA transcript junctions.
Methods
Twenty-five CML samples were analyzed in two different ISO15189-accredited centers that both use an Europe Against Cancer-based quantitative polymerase chain reaction (qPCR) protocol. Reanalysis of the sample set with transcript-specific standard curves and digital droplet PCR (ddPCR) were performed.
Results
qPCR quantification revealed a significant (up to 1 log) difference specifically for the e13a2 transcript variant in contrast to e14a2 transcripts (Hodges–Lehman 4.29; p < 0.001). Reanalysis of the sample set with transcript-specific standard curves abolishes the initial transcript-specific difference (Hodges–Lehman 0.003; p = 0.8192). Comparison of transcript-specific qPCR results of both centers with ddPCR, an absolute quantification method, showed a statically significant association, especially in the lower range, indicating the clinical utility of transcript-specific or absolute quantification methods.
Conclusion
Our data show that differences between transcript-specific quantification might exist between centers, leading to potential clinical impact on the follow-up of CML patients. The use of transcript-specific standard curves for qPCR quantification, or absolute quantification, can significantly reduce these differences. Specific attention should be applied to the interpretation of quantification differences of CML patients that switch between diagnostic centers.
{"title":"Variant-specific BCR::ABL1 quantification discrepancy in chronic myeloid leukemia","authors":"Koen Jacobs, Alena Moerman, Karl Vandepoele, Tim Van den Abeele, Katrien De Mulder, Eva Steel, Maxim Clauwaert, Henk Louagie","doi":"10.1111/ijlh.14320","DOIUrl":"10.1111/ijlh.14320","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Accurate quantification of the <i>BCR::ABL1</i> fusion gene in whole blood is pivotal for the clinical management of chronic myeloid leukemia (CML) patients. The fusion protein encoded by <i>BCR::ABL1</i> can vary in size, depending on the <i>BCR</i> and/or <i>ABL1</i> gene breakpoint. The vast majority of CML patients have a p210 <i>BCR::ABL1</i> fusion gene (M-BCR), which can be attributed to the presence of either e14a2 (b3a2) or e13a2 (b2a2) mRNA transcript junctions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Twenty-five CML samples were analyzed in two different ISO15189-accredited centers that both use an Europe Against Cancer-based quantitative polymerase chain reaction (qPCR) protocol. Reanalysis of the sample set with transcript-specific standard curves and digital droplet PCR (ddPCR) were performed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>qPCR quantification revealed a significant (up to 1 log) difference specifically for the e13a2 transcript variant in contrast to e14a2 transcripts (Hodges–Lehman 4.29; <i>p</i> < 0.001). Reanalysis of the sample set with transcript-specific standard curves abolishes the initial transcript-specific difference (Hodges–Lehman 0.003; <i>p</i> = 0.8192). Comparison of transcript-specific qPCR results of both centers with ddPCR, an absolute quantification method, showed a statically significant association, especially in the lower range, indicating the clinical utility of transcript-specific or absolute quantification methods.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our data show that differences between transcript-specific quantification might exist between centers, leading to potential clinical impact on the follow-up of CML patients. The use of transcript-specific standard curves for qPCR quantification, or absolute quantification, can significantly reduce these differences. Specific attention should be applied to the interpretation of quantification differences of CML patients that switch between diagnostic centers.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14120,"journal":{"name":"International Journal of Laboratory Hematology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141260734","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}
Fei Gao, Shuang Chen, Jianwei Li, Zailin Yang, Cui Mao
<p>T-cell prolymphocytic leukemia (T-PLL) is a very rare subtype of the mature lymphocytic malignancies that typically occur in middle-aged and older individuals, accounting for approximately 2% of all mature T-cell lymphomas.<span><sup>1</sup></span> T-PLL is characterized by a poor median survival rate and distinctive cell morphological, immunophenotypic, and cytogenetic features. The major diagnostic criteria of the guidelines for T-PLL diagnosis<span><sup>2</sup></span> include: (1) 5 × 10<sup>9</sup>/L cells of the T-PLL phenotype in peripheral blood or bone marrow (BM); (2) T-cell clonality determined via PCR or flow cytometry (FCM); and, (3) an abnormal 14q32 or Xq28 karyotype or expression of <i>TCL1A/B</i> or <i>MTCP1</i>. Additionally, four minor criteria also contribute to the diagnostic framework: (1) abnormalities involving chromosome 11 (11q22.3; <i>ATM</i>); (2) abnormalities involving chromosome 8 such as idic(8)(p11), t(8;8), trisomy 8q; (3) abnormalities in chromosomes 5, 12, 13, 22, or a complex karyotype; and, (4) T-PLL-specific features (e.g., splenomegaly, effusions). A diagnosis of T-PLL is established if all three major criteria are met or if the first two such criteria and at least one minor criterion are met. Obviously, analysis of chromosomal abnormalities is essential for diagnosis of T-PLL. However, T-PLL poses a challenge in this regard given the low proliferation capacity of mature T lymphocytes, leading to a high failure rate of chromosomal karyotyping associated with conventional culture methods (short-term culture).</p><p>In this study, we retrospectively analyze and present five cases for whom we used a phytohemagglutinin (PHA)-stimulated culture method to increase the detection rate of chromosomal abnormalities in BM cells. This enhanced T-PLL diagnostic accuracy.</p><p>All five patients were males of median age 58 years (range, 42 to 83 years). Immunophenotypic abnormalities were observed in 50% ~ 90% of T cells of all patients (Table S1) in BM sample. Most exhibited the phenotype CD3<sup>+</sup>, CD2<sup>+</sup>, CD4<sup>+</sup>, CD5<sup>+</sup>, CD7<sup>+</sup>, CD56<sup>−</sup>, CD34<sup>−</sup>, CD117<sup>−</sup>, CD1a<sup>−</sup>, and CD52<sup>+</sup>. The most notable immunophenotypic difference was that for CD8: cases 1, 4, and 5 were of CD8<sup>part+</sup> status; case 2 CD8<sup>−</sup>; and case 3 CD8<sup>+</sup>. Subsequently, chromosomal karyotyping was performed on cultures grown with and without PHA (Table 1). Three of the five patients (cases 1, 2, and 3) exhibited only a 46,XY karyotype when cells were grown without PHA, but complex karyotypes, inv(14), trisomy 8q, and abnormalities in 11q when cells were grown with PHA. One patient (case 5) exhibited no metaphase cells when cells were grown without PHA, but a complex karyotype, abnormalities in 11q, and t (14;14) when cells were grown with PHA. Only one patient (case 4) yielded consistent chromosomal karyotypes when cells were grown with and wi
12 我们的研究结果有助于加深对 T-PLL 的遗传和分子机制的理解，我们还对可能影响疾病进展和表现的因素提出了见解。首先，这项研究属于回顾性研究。其次，我们缺乏年龄匹配的健康对照组的核型数据，因为从健康受试者身上收集骨髓是不道德的。第三，3 名涉及 7 号和 14 号染色体异常的 T-PLL 患者没有进行 FISH 检测。总之，使用 PHA 刺激培养物进行染色体核型分析可能是筛查成熟 T 淋巴细胞异常核型的一大进步。我们的研究强调了在临床环境中使用 PHA 刺激的 BM 细胞培养物对成熟 T 淋巴细胞克隆疑似异常的患者进行染色体核型分析的必要性。当检测到诊断异常时，可进行进一步的确证试验。F.G、C.M和Z.Y参与了研究的构思。F.G、S.C和J.L参与了实验分析、数据解释和讨论。C.M 和 Z.Y 参与了临床决策。所有作者均审阅并批准了最终手稿。
{"title":"The critical role of phytohemagglutinin-stimulated cell cultures in the diagnosis of T-cell prolymphocytic leukemia: A case-based approach","authors":"Fei Gao, Shuang Chen, Jianwei Li, Zailin Yang, Cui Mao","doi":"10.1111/ijlh.14323","DOIUrl":"10.1111/ijlh.14323","url":null,"abstract":"<p>T-cell prolymphocytic leukemia (T-PLL) is a very rare subtype of the mature lymphocytic malignancies that typically occur in middle-aged and older individuals, accounting for approximately 2% of all mature T-cell lymphomas.<span><sup>1</sup></span> T-PLL is characterized by a poor median survival rate and distinctive cell morphological, immunophenotypic, and cytogenetic features. The major diagnostic criteria of the guidelines for T-PLL diagnosis<span><sup>2</sup></span> include: (1) 5 × 10<sup>9</sup>/L cells of the T-PLL phenotype in peripheral blood or bone marrow (BM); (2) T-cell clonality determined via PCR or flow cytometry (FCM); and, (3) an abnormal 14q32 or Xq28 karyotype or expression of <i>TCL1A/B</i> or <i>MTCP1</i>. Additionally, four minor criteria also contribute to the diagnostic framework: (1) abnormalities involving chromosome 11 (11q22.3; <i>ATM</i>); (2) abnormalities involving chromosome 8 such as idic(8)(p11), t(8;8), trisomy 8q; (3) abnormalities in chromosomes 5, 12, 13, 22, or a complex karyotype; and, (4) T-PLL-specific features (e.g., splenomegaly, effusions). A diagnosis of T-PLL is established if all three major criteria are met or if the first two such criteria and at least one minor criterion are met. Obviously, analysis of chromosomal abnormalities is essential for diagnosis of T-PLL. However, T-PLL poses a challenge in this regard given the low proliferation capacity of mature T lymphocytes, leading to a high failure rate of chromosomal karyotyping associated with conventional culture methods (short-term culture).</p><p>In this study, we retrospectively analyze and present five cases for whom we used a phytohemagglutinin (PHA)-stimulated culture method to increase the detection rate of chromosomal abnormalities in BM cells. This enhanced T-PLL diagnostic accuracy.</p><p>All five patients were males of median age 58 years (range, 42 to 83 years). Immunophenotypic abnormalities were observed in 50% ~ 90% of T cells of all patients (Table S1) in BM sample. Most exhibited the phenotype CD3<sup>+</sup>, CD2<sup>+</sup>, CD4<sup>+</sup>, CD5<sup>+</sup>, CD7<sup>+</sup>, CD56<sup>−</sup>, CD34<sup>−</sup>, CD117<sup>−</sup>, CD1a<sup>−</sup>, and CD52<sup>+</sup>. The most notable immunophenotypic difference was that for CD8: cases 1, 4, and 5 were of CD8<sup>part+</sup> status; case 2 CD8<sup>−</sup>; and case 3 CD8<sup>+</sup>. Subsequently, chromosomal karyotyping was performed on cultures grown with and without PHA (Table 1). Three of the five patients (cases 1, 2, and 3) exhibited only a 46,XY karyotype when cells were grown without PHA, but complex karyotypes, inv(14), trisomy 8q, and abnormalities in 11q when cells were grown with PHA. One patient (case 5) exhibited no metaphase cells when cells were grown without PHA, but a complex karyotype, abnormalities in 11q, and t (14;14) when cells were grown with PHA. Only one patient (case 4) yielded consistent chromosomal karyotypes when cells were grown with and wi","PeriodicalId":14120,"journal":{"name":"International Journal of Laboratory Hematology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ijlh.14323","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141260585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xue-Shen Yan, Yu-Jiao Sun, Juan Du, Wen-Yan Niu, Han Qiao, Xiang-Cong Yin
<div> <section> <h3> Introduction</h3> <p>The purpose of this study was to investigate the effects and potential mechanisms of ferroptosis-related gene heat shock protein beta-1 (HSPB1) on acute myeloid leukemia (AML).</p> </section> <section> <h3> Methods</h3> <p>The RNA-seq and clinical data of AML samples were obtained from the Genomic Data Commons database, and the FerrDb database was used to screen the marker, drive and suppressor of ferroptosis. Besides, DESeq2 was applied for differential expression analysis on AML samples and screening for differentially expressed genes (DEGs). The screened DEGs were subjected to the intersection analysis with ferroptosis-related genes to identify the ferroptosis-related DEGs. Next, the functional pathways of ferroptosis-related DEGs were further be discussed by Gene Ontology as well as Kyoto Encyclopedia of Genes and Genomes enrichment analysis of DEGs. Additionally, lasso regression analysis was employed to determine the differential genes related to prognosis in patients with AML and the survival analysis was performed. Subsequently, quantitative real-time polymerase chain reaction and western blot assay were applied to detect the mRNA and protein expression levels of HSPB1 in normal/AML bone marrow tissues and human normal (HS-5)/AML (HL-60) bone marrow cells, respectively. Furthermore, HSPB1 was knocked down to assess the expression changes of glutathione peroxidase 4 and acyl-CoA synthetase long-chain family member 4. Ultimately, the viability and oxidative stress levels of HL-60 were analyzed by Cell Counting Kit-8 and biochemical detection.</p> </section> <section> <h3> Results</h3> <p>A total of 4986 DEGs were identified in AML samples, with 3324 up-regulated and 1662 down-regulated. The enrichment analysis illustrated that ferroptosis-related DEGs were significantly enriched in response to metal irons, oxidative stress, and other pathways. After lasso regression analysis, 17 feature genes related to the prognosis of patients with AML were obtained, with HSPB1 exhibiting a significant correlation. The reliability of our models was verified by Cox regression analysis and survival analysis of the hazard model. Furthermore, the outcomes of quantitative real-time polymerase chain reaction and western blot showed that mRNA and protein expression levels of HSPB1 were significantly increased in the AML Group and HL-60 cells. The knockdown of HSPB1 in HL-60 cells reduced the protein level of glutathione peroxidase 4, increased the protein level of acyl-CoA synthetase long-chain family member 4, decreased the cell viability, and aggravated oxidative stress.</p> </section> <section> <h3> Conclusion</h3>
{"title":"Effects of ferroptosis-related gene HSPB1 on acute myeloid leukemia","authors":"Xue-Shen Yan, Yu-Jiao Sun, Juan Du, Wen-Yan Niu, Han Qiao, Xiang-Cong Yin","doi":"10.1111/ijlh.14319","DOIUrl":"10.1111/ijlh.14319","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>The purpose of this study was to investigate the effects and potential mechanisms of ferroptosis-related gene heat shock protein beta-1 (HSPB1) on acute myeloid leukemia (AML).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The RNA-seq and clinical data of AML samples were obtained from the Genomic Data Commons database, and the FerrDb database was used to screen the marker, drive and suppressor of ferroptosis. Besides, DESeq2 was applied for differential expression analysis on AML samples and screening for differentially expressed genes (DEGs). The screened DEGs were subjected to the intersection analysis with ferroptosis-related genes to identify the ferroptosis-related DEGs. Next, the functional pathways of ferroptosis-related DEGs were further be discussed by Gene Ontology as well as Kyoto Encyclopedia of Genes and Genomes enrichment analysis of DEGs. Additionally, lasso regression analysis was employed to determine the differential genes related to prognosis in patients with AML and the survival analysis was performed. Subsequently, quantitative real-time polymerase chain reaction and western blot assay were applied to detect the mRNA and protein expression levels of HSPB1 in normal/AML bone marrow tissues and human normal (HS-5)/AML (HL-60) bone marrow cells, respectively. Furthermore, HSPB1 was knocked down to assess the expression changes of glutathione peroxidase 4 and acyl-CoA synthetase long-chain family member 4. Ultimately, the viability and oxidative stress levels of HL-60 were analyzed by Cell Counting Kit-8 and biochemical detection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 4986 DEGs were identified in AML samples, with 3324 up-regulated and 1662 down-regulated. The enrichment analysis illustrated that ferroptosis-related DEGs were significantly enriched in response to metal irons, oxidative stress, and other pathways. After lasso regression analysis, 17 feature genes related to the prognosis of patients with AML were obtained, with HSPB1 exhibiting a significant correlation. The reliability of our models was verified by Cox regression analysis and survival analysis of the hazard model. Furthermore, the outcomes of quantitative real-time polymerase chain reaction and western blot showed that mRNA and protein expression levels of HSPB1 were significantly increased in the AML Group and HL-60 cells. The knockdown of HSPB1 in HL-60 cells reduced the protein level of glutathione peroxidase 4, increased the protein level of acyl-CoA synthetase long-chain family member 4, decreased the cell viability, and aggravated oxidative stress.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 ","PeriodicalId":14120,"journal":{"name":"International Journal of Laboratory Hematology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141201589","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}
The global burden of multiple myeloma (MM) is increasing every year. Here, we have developed machine learning models to provide a reference for the early detection of MM.
Methods
A total of 465 patients and 150 healthy controls were enrolled in this retrospective study. Based on the variable screening strategy of least absolute shrinkage and selection operator (LASSO), three prediction models, logistic regression (LR), support vector machine (SVM), and random forest (RF), were established combining complete blood count (CBC) and cell population data (CPD) parameters in the training set (210 cases), and were verified in the validation set (90 cases) and test set (165 cases). The performance of each model was analyzed using receiver operating characteristic (ROC) curve, calibration curves, and decision curve analysis (DCA). Accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and area under the ROC curve (AUC) were applied to evaluate the models. Delong test was used to compare the AUC of the models.
Results
Six parameters including RBC (1012/L), RDW-CV (%), IG (%), NE-WZ, LY-WX, and LY-WZ were screened out by LASSO to construct the model. Among the three models, the AUC of RF model in the training set, validation set, and test set were 0.956, 0.892, and 0.875, which were higher than those of LR model (0.901, 0.849, and 0.858) and SVM model (0.929, 0.868, and 0.846). Delong test showed that there were significant differences among the models in the training set, no significant differences in the validation set, and significant differences only between SVM and RF models in the test set. The calibration curve and DCA showed that the three models had good validity and feasibility, and the RF model performed best.
Conclusion
The proposed RF model may be a useful auxiliary tool for rapid screening of MM patients.
{"title":"Construction of the prediction model for multiple myeloma based on machine learning","authors":"Jiangying Cai, Zhenhua Liu, Yingying Wang, Wanxia Yang, Zhipeng Sun, Chongge You","doi":"10.1111/ijlh.14324","DOIUrl":"10.1111/ijlh.14324","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>The global burden of multiple myeloma (MM) is increasing every year. Here, we have developed machine learning models to provide a reference for the early detection of MM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A total of 465 patients and 150 healthy controls were enrolled in this retrospective study. Based on the variable screening strategy of least absolute shrinkage and selection operator (LASSO), three prediction models, logistic regression (LR), support vector machine (SVM), and random forest (RF), were established combining complete blood count (CBC) and cell population data (CPD) parameters in the training set (210 cases), and were verified in the validation set (90 cases) and test set (165 cases). The performance of each model was analyzed using receiver operating characteristic (ROC) curve, calibration curves, and decision curve analysis (DCA). Accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and area under the ROC curve (AUC) were applied to evaluate the models. Delong test was used to compare the AUC of the models.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Six parameters including RBC (10<sup>12</sup>/L), RDW-CV (%), IG (%), NE-WZ, LY-WX, and LY-WZ were screened out by LASSO to construct the model. Among the three models, the AUC of RF model in the training set, validation set, and test set were 0.956, 0.892, and 0.875, which were higher than those of LR model (0.901, 0.849, and 0.858) and SVM model (0.929, 0.868, and 0.846). Delong test showed that there were significant differences among the models in the training set, no significant differences in the validation set, and significant differences only between SVM and RF models in the test set. The calibration curve and DCA showed that the three models had good validity and feasibility, and the RF model performed best.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The proposed RF model may be a useful auxiliary tool for rapid screening of MM patients.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14120,"journal":{"name":"International Journal of Laboratory Hematology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141186952","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}
Henriette Røed-Undlien, Nina Haagenrud Schultz, Erik Koldberg Amundsen, Birgit M. Wollmann, Espen Molden, Rupali R. Akerkar, Johannes Lagethon Bjørnstad
Introduction
Hemolytic interference may impact various laboratory tests, including coagulation analyses. Apixaban is the most commonly used direct oral anticoagulant in Norway, and there is lacking knowledge on how apixaban concentration measurements might be influenced by hemolysis. Moreover, hemolysis-induced alterations in apixaban levels could potentially impact the risk of bleeding in specific clinical scenarios. We wanted to study whether hemolysis would increase apixaban concentration and investigate the impact of hemolytic interference on apixaban concentration measurements.
Methods
Blood samples from 20 apixaban-treated patients and 8 healthy controls were hemolyzed in vitro by a freeze method. The degree of hemolysis was measured with plasma free hemoglobin (PfHb) at baseline and two levels of hemolysis. Apixaban concentration was measured in plasma using both the chromogenic anti-Xa method and the ultraperformance liquid chromatography mass spectrometry (UPLC-MS). Thrombin generation assay was performed to assess coagulability.
Results
UPLC-MS measurements showed a mean concentration change of −1.66% (±3.2%, p = 0.005) and anti-Xa assay showed a mean concentration change of 3.37% (±6.5%, p = 0.09) with increasing hemolysis. Thrombin generation lagtime decreased, and endogenous thrombin potential and peak thrombin increased with increasing hemolysis in both the control group and the apixaban group.
Conclusion
Apixaban concentration measurements by anti-Xa assay and UPLC-MS were not affected by hemolysis to a clinically relevant extent. Furthermore, hemolysis did not lead to hypocoagulability when assessed by thrombin generation.
导言溶血干扰可能会影响各种实验室检测，包括凝血分析。阿哌沙班是挪威最常用的直接口服抗凝剂，目前还不清楚溶血会如何影响阿哌沙班的浓度测量。此外，溶血引起的阿哌沙班浓度变化可能会影响特定临床情况下的出血风险。我们希望研究溶血是否会增加阿哌沙班的浓度，并调查溶血干扰对阿哌沙班浓度测量的影响：方法：采用冷冻法对 20 名阿哌沙班治疗患者和 8 名健康对照者的血样进行体外溶血。用血浆游离血红蛋白（PfHb）测量基线和两个溶血水平的溶血程度。血浆中的阿哌沙班浓度采用显色抗 Xa 法和超高效液相色谱质谱法（UPLC-MS）进行测定。进行凝血酶生成测定以评估凝血能力：超高效液相色谱-质谱测定显示，随着溶血量的增加，平均浓度变化为-1.66%（±3.2%，p = 0.005），抗 Xa 检测显示平均浓度变化为 3.37%（±6.5%，p = 0.09）。对照组和阿哌沙班组随着溶血量的增加，凝血酶生成滞后时间减少，内源性凝血酶潜能和凝血酶峰值增加：通过抗 Xa 检测法和超高效液相色谱-质谱法测量的阿哌沙班浓度不会受到溶血的临床影响。此外，通过凝血酶生成评估溶血并不会导致低凝状态。
{"title":"Does in vitro hemolysis affect measurements of plasma apixaban concentration by UPLC-MS and anti-Xa assay?","authors":"Henriette Røed-Undlien, Nina Haagenrud Schultz, Erik Koldberg Amundsen, Birgit M. Wollmann, Espen Molden, Rupali R. Akerkar, Johannes Lagethon Bjørnstad","doi":"10.1111/ijlh.14311","DOIUrl":"10.1111/ijlh.14311","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Hemolytic interference may impact various laboratory tests, including coagulation analyses. Apixaban is the most commonly used direct oral anticoagulant in Norway, and there is lacking knowledge on how apixaban concentration measurements might be influenced by hemolysis. Moreover, hemolysis-induced alterations in apixaban levels could potentially impact the risk of bleeding in specific clinical scenarios. We wanted to study whether hemolysis would increase apixaban concentration and investigate the impact of hemolytic interference on apixaban concentration measurements.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Blood samples from 20 apixaban-treated patients and 8 healthy controls were hemolyzed in vitro by a freeze method. The degree of hemolysis was measured with plasma free hemoglobin (PfHb) at baseline and two levels of hemolysis. Apixaban concentration was measured in plasma using both the chromogenic anti-Xa method and the ultraperformance liquid chromatography mass spectrometry (UPLC-MS). Thrombin generation assay was performed to assess coagulability.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>UPLC-MS measurements showed a mean concentration change of −1.66% (±3.2%, <i>p</i> = 0.005) and anti-Xa assay showed a mean concentration change of 3.37% (±6.5%, <i>p</i> = 0.09) with increasing hemolysis. Thrombin generation lagtime decreased, and endogenous thrombin potential and peak thrombin increased with increasing hemolysis in both the control group and the apixaban group.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Apixaban concentration measurements by anti-Xa assay and UPLC-MS were not affected by hemolysis to a clinically relevant extent. Furthermore, hemolysis did not lead to hypocoagulability when assessed by thrombin generation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14120,"journal":{"name":"International Journal of Laboratory Hematology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ijlh.14311","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141163149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sophie Melicine, Capucine Habay, Wiame Ghammad, Julie Carré, Jean Luc Diehl, David M. Smadja, Nicolas Gendron, Dominique Helley, Laetitia Mauge
Introduction
The monitoring of unfractionated heparin (UFH) by anti-factor Xa activity (AXA) is commonly used to ensure effective anticoagulation and prevent bleeding risk. However, in patients previously treated with an anti-Xa direct oral anticoagulant (DOAC) switching to UFH therapy, there is a risk of interference that may lead to inappropriate anticoagulation. The first objective of this study was to validate DOAC-Remove to remove DOAC for measuring UFH specific AXA. The second objective was to assess the length of DOAC interference on UFH monitoring and to identify potential predictive factors.
Materials and Methods
This monocentric retrospective study included all patients admitted from April 2019 to April 2021 previously treated with anti-Xa DOAC, and for whom an interference on UFH monitoring was suspected. Interference was defined as a difference in the AXA measured before and after using DOAC-Remove >2.8-fold standard deviation of the method.
Results
Removal with DOAC-Remove was specific of DOAC (apixaban n = 42, rivaroxaban n = 41, UFH n = 20) and sufficient to avoid interference on UFH AXA measurement. The exact interference length was 6.0 days [IQR 3.0–11.0] for apixaban (n = 26) and 4.5 days [IQR 2.0–5.8] for rivaroxaban (n = 20). Among the 89 patients sorted based on an interference length ≤ or >3 days, 74 (83.1%) presented an interference greater than 3 days. Correlations were observed with age for apixaban and creatinine for rivaroxaban.
Conclusions
Our results suggest that DOAC-Remove could be of high interest in patients receiving UFH previously treated with an anti-Xa DOAC even if DOAC was stopped for more than 3 days.
{"title":"DOAC-Remove to counteract the interference of anti-Xa oral anticoagulants on the monitoring of heparin","authors":"Sophie Melicine, Capucine Habay, Wiame Ghammad, Julie Carré, Jean Luc Diehl, David M. Smadja, Nicolas Gendron, Dominique Helley, Laetitia Mauge","doi":"10.1111/ijlh.14321","DOIUrl":"10.1111/ijlh.14321","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>The monitoring of unfractionated heparin (UFH) by anti-factor Xa activity (AXA) is commonly used to ensure effective anticoagulation and prevent bleeding risk. However, in patients previously treated with an anti-Xa direct oral anticoagulant (DOAC) switching to UFH therapy, there is a risk of interference that may lead to inappropriate anticoagulation. The first objective of this study was to validate DOAC-Remove to remove DOAC for measuring UFH specific AXA. The second objective was to assess the length of DOAC interference on UFH monitoring and to identify potential predictive factors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Materials and Methods</h3>\u0000 \u0000 <p>This monocentric retrospective study included all patients admitted from April 2019 to April 2021 previously treated with anti-Xa DOAC, and for whom an interference on UFH monitoring was suspected. Interference was defined as a difference in the AXA measured before and after using DOAC-Remove >2.8-fold standard deviation of the method.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Removal with DOAC-Remove was specific of DOAC (apixaban <i>n</i> = 42, rivaroxaban <i>n</i> = 41, UFH <i>n</i> = 20) and sufficient to avoid interference on UFH AXA measurement. The exact interference length was 6.0 days [IQR 3.0–11.0] for apixaban (<i>n</i> = 26) and 4.5 days [IQR 2.0–5.8] for rivaroxaban (<i>n</i> = 20). Among the 89 patients sorted based on an interference length ≤ or >3 days, 74 (83.1%) presented an interference greater than 3 days. Correlations were observed with age for apixaban and creatinine for rivaroxaban.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our results suggest that DOAC-Remove could be of high interest in patients receiving UFH previously treated with an anti-Xa DOAC even if DOAC was stopped for more than 3 days.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14120,"journal":{"name":"International Journal of Laboratory Hematology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141159326","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}
Shi Tao, Qianlei Huang, Weilun Zhou, Jing Chen, Yuxuan Man, Lang Chen, Yu Chen
Background
Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma, which caused many patients to lose their precious lives. FOXO3 was a suppressor in various cancers, however, the role and mechanism of FOXO3 in DLBCL remain unclear.
Methods
Bioinformatics analysis was used to offer information FOXO3 expression and its expression for prognosis of DLBCL patients. The abundance of genes and proteins was evaluated using RT-qPCR and western blot. Cell proliferation and apoptosis was detected by CCK-8 and flow cytometry. The interactions among FOXO3, miR-34b, and HSPG2 were predicted by TransmiR and Starbase and validated using dual luciferase reporter assay, ChIP assay, and RIP assay.
Results
Our findings revealed that FOXO3 expression was abnormally declined in DLBCL cells. FOXO3 upregulation restrained cell proliferation and promoted cell apoptosis of DLBCL cells, while miR-34b inhibitor eliminated these influences. Similarly, miR-34b mimic suppressed malignant behaviors of DLBCL cells, which were abolished by HSPG2 overexpression. Mechanically, FOXO3 induced miR-34b expression through interacting with miR-34b promoter and HSPG2 was a targeted gene of miR-34b.
Conclusion
FOXO3 attenuated the capability of cell proliferation and promoted cell apoptosis rate of DLBCL cells through affecting miR-34b/HSPG2 axis, therefore inhibiting DLBCL progression.
背景：弥漫大 B 细胞淋巴瘤（DLBCL弥漫大B细胞淋巴瘤（DLBCL）是最常见的淋巴瘤类型，它使许多患者失去了宝贵的生命。FOXO3是多种癌症的抑制因子，然而，FOXO3在DLBCL中的作用和机制仍不清楚：方法：利用生物信息学分析提供 FOXO3 的表达及其对 DLBCL 患者预后的影响。采用 RT-qPCR 和 Western 印迹技术评估了基因和蛋白质的丰度。CCK-8和流式细胞术检测了细胞的增殖和凋亡。TransmiR和Starbase预测了FOXO3、miR-34b和HSPG2之间的相互作用，并使用双荧光素酶报告实验、ChIP实验和RIP实验进行了验证：结果：我们的研究结果表明，FOXO3在DLBCL细胞中的表达异常下降。FOXO3的上调抑制了DLBCL细胞的增殖并促进了细胞凋亡，而miR-34b抑制剂则消除了这些影响。同样，miR-34b模拟物抑制了DLBCL细胞的恶性行为，而HSPG2的过表达则消除了这些行为。从机理上讲，FOXO3通过与miR-34b启动子相互作用诱导miR-34b的表达，而HSPG2是miR-34b的靶基因：结论：FOXO3通过影响miR-34b/HSPG2轴，减弱了DLBCL细胞的增殖能力，促进了细胞凋亡率，从而抑制了DLBCL的进展。
{"title":"FOXO3 suppresses lymphoma progression through promoting miR-34b/HSPG2 axis","authors":"Shi Tao, Qianlei Huang, Weilun Zhou, Jing Chen, Yuxuan Man, Lang Chen, Yu Chen","doi":"10.1111/ijlh.14310","DOIUrl":"10.1111/ijlh.14310","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Diffuse large B-cell lymphoma (DLBCL) is the most common type of lymphoma, which caused many patients to lose their precious lives. FOXO3 was a suppressor in various cancers, however, the role and mechanism of FOXO3 in DLBCL remain unclear.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Bioinformatics analysis was used to offer information FOXO3 expression and its expression for prognosis of DLBCL patients. The abundance of genes and proteins was evaluated using RT-qPCR and western blot. Cell proliferation and apoptosis was detected by CCK-8 and flow cytometry. The interactions among FOXO3, miR-34b, and HSPG2 were predicted by TransmiR and Starbase and validated using dual luciferase reporter assay, ChIP assay, and RIP assay.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Our findings revealed that FOXO3 expression was abnormally declined in DLBCL cells. FOXO3 upregulation restrained cell proliferation and promoted cell apoptosis of DLBCL cells, while miR-34b inhibitor eliminated these influences. Similarly, miR-34b mimic suppressed malignant behaviors of DLBCL cells, which were abolished by HSPG2 overexpression. Mechanically, FOXO3 induced miR-34b expression through interacting with miR-34b promoter and HSPG2 was a targeted gene of miR-34b.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>FOXO3 attenuated the capability of cell proliferation and promoted cell apoptosis rate of DLBCL cells through affecting miR-34b/HSPG2 axis, therefore inhibiting DLBCL progression.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14120,"journal":{"name":"International Journal of Laboratory Hematology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141077421","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}
{"title":"Issue Information Covers","authors":"","doi":"10.1111/ijlh.14309","DOIUrl":"https://doi.org/10.1111/ijlh.14309","url":null,"abstract":"","PeriodicalId":14120,"journal":{"name":"International Journal of Laboratory Hematology","volume":null,"pages":null},"PeriodicalIF":3.0,"publicationDate":"2024-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/ijlh.14309","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141069105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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