Small molecules UM171 and SR1 have already been taken into clinically-oriented protocols for the ex vivo expansion of hematopoietic stem (HSCs) and progenitor (HPCs) cells. In order to gain further insight into their biology, in the present study we have assessed their effects, both individually and in combination, on the in vitro long-term proliferation and expansion of HSCs and HPCs contained within three different cord blood-derived cell populations: MNCs (CD34+ cells = 0.8 %), LIN− cells (CD34+ cells = 41 %), and CD34+ cells (CD34+ cells >98 %). Our results show that when added to cultures in the absence of recombinant stimulatory cytokines, neither molecule had any effect. In contrast, when added in the presence of hematopoietic cytokines, UM171 and SR1 had significant stimulatory effects on cell proliferation and expansion in cultures of LIN− and CD34+ cells. No significant effects were observed in cultures of MNCs. The effects of both molecules were more pronounced in cultures with the highest proportion of CD34+ cells, and the greatest effects were observed when both molecules were added in combination. In the absence of small molecules, cell numbers reached a peak by days 25–30, and then declined; whereas in the presence of UM171 or/and SR1 cell numbers were sustained up to day 45 of culture. Our results indicate that besides CD34+ cells, LIN− cells could also be used as input cells in clinically-oriented expansion protocols, and that using both molecules simultaneously would be a better approach than using only one of them.
{"title":"Further biological characterization of small molecules UM171 and SR1: In vitro effects on three hematopoietic cell populations from human cord blood","authors":"Patricia Flores-Guzman, Aranxa Torres-Caballero, Hector Mayani","doi":"10.1016/j.bcmd.2024.102895","DOIUrl":"10.1016/j.bcmd.2024.102895","url":null,"abstract":"<div><div>Small molecules UM171 and SR1 have already been taken into clinically-oriented protocols for the ex vivo expansion of hematopoietic stem (HSCs) and progenitor (HPCs) cells. In order to gain further insight into their biology, in the present study we have assessed their effects, both individually and in combination, on the in vitro long-term proliferation and expansion of HSCs and HPCs contained within three different cord blood-derived cell populations: MNCs (CD34<sup>+</sup> cells = 0.8 %), LIN<sup>−</sup> cells (CD34<sup>+</sup> cells = 41 %), and CD34<sup>+</sup> cells (CD34<sup>+</sup> cells >98 %). Our results show that when added to cultures in the absence of recombinant stimulatory cytokines, neither molecule had any effect. In contrast, when added in the presence of hematopoietic cytokines, UM171 and SR1 had significant stimulatory effects on cell proliferation and expansion in cultures of LIN<sup>−</sup> and CD34<sup>+</sup> cells. No significant effects were observed in cultures of MNCs. The effects of both molecules were more pronounced in cultures with the highest proportion of CD34<sup>+</sup> cells, and the greatest effects were observed when both molecules were added in combination. In the absence of small molecules, cell numbers reached a peak by days 25–30, and then declined; whereas in the presence of UM171 or/and SR1 cell numbers were sustained up to day 45 of culture. Our results indicate that besides CD34<sup>+</sup> cells, LIN<sup>−</sup> cells could also be used as input cells in clinically-oriented expansion protocols, and that using both molecules simultaneously would be a better approach than using only one of them.</div></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"110 ","pages":"Article 102895"},"PeriodicalIF":2.1,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280115","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}
Pub Date : 2024-09-18DOI: 10.1016/j.bcmd.2024.102894
Mana Mitsutani , Mei Yokoyama , Hiromi Hano , Aoi Morita , Midori Matsushita , Tetsuya Tagami , Kenji Moriyama
GATAs are a family of transcription factors consisting of six members. Particularly, GATA1 and GATA2 have been reported to promote the development of erythrocytes, megakaryocytes, eosinophils, and mast cells. However, little information is available on the extracellular ligands that promote GATA1 expression. We evaluated whether growth hormone (GH) is an extracellular stimulator that participates in the signal transduction of GATAs, focusing on GATA1 expression in hematopoietic cell lineages. We used a reporter assay, RT-PCR, real-time quantitative PCR, and western blotting to evaluate GH-induced expression of GATA1 and GATA2 in the human erythroleukemic cell line K562 and the non-erythroid cell line U937. GATA1 expression in these hematopoietic cell lines increased at the transcriptional and protein levels in the presence of GH, and was inhibited by a STAT5 specific inhibitor. Cells transfected with activated STAT5B showed increased expression of GATA1. We identified functional STAT5B consensus sequences as binding site-158 bp from the transcription starting site in the GATA1 promoter region. These results suggest that GH directly induces GATA1 expression via GHR/JAK/STAT5 and is related to hematopoietic cell proliferation.
{"title":"Growth hormone is involved in GATA1 gene expression via STAT5B in human erythroleukemia and monocytic cell lines","authors":"Mana Mitsutani , Mei Yokoyama , Hiromi Hano , Aoi Morita , Midori Matsushita , Tetsuya Tagami , Kenji Moriyama","doi":"10.1016/j.bcmd.2024.102894","DOIUrl":"10.1016/j.bcmd.2024.102894","url":null,"abstract":"<div><div>GATAs are a family of transcription factors consisting of six members. Particularly, GATA1 and GATA2 have been reported to promote the development of erythrocytes, megakaryocytes, eosinophils, and mast cells. However, little information is available on the extracellular ligands that promote GATA1 expression. We evaluated whether growth hormone (GH) is an extracellular stimulator that participates in the signal transduction of GATAs, focusing on GATA1 expression in hematopoietic cell lineages. We used a reporter assay, RT-PCR, real-time quantitative PCR, and western blotting to evaluate GH-induced expression of GATA1 and GATA2 in the human erythroleukemic cell line K562 and the non-erythroid cell line U937. GATA1 expression in these hematopoietic cell lines increased at the transcriptional and protein levels in the presence of GH, and was inhibited by a STAT5 specific inhibitor. Cells transfected with activated STAT5B showed increased expression of GATA1. We identified functional STAT5B consensus sequences as binding site-158 bp from the transcription starting site in the GATA1 promoter region. These results suggest that GH directly induces GATA1 expression via GHR/JAK/STAT5 and is related to hematopoietic cell proliferation.</div></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"110 ","pages":"Article 102894"},"PeriodicalIF":2.1,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280116","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}
Pub Date : 2024-09-10DOI: 10.1016/j.bcmd.2024.102893
Sean X. Gu , Ayesha Butt , Vincent P. Schulz , Henry M. Rinder , Alfred I. Lee , Patrick G. Gallagher , John Hwa , Robert D. Bona
Inherited platelet disorders (IPDs) are a heterogeneous group of conditions that present significant challenges in diagnosis and management. Here, we report two cases of patients presenting with clinically significant bleeding but with unclear etiologies by conventional clinical laboratory testing. Further evaluation, utilizing a combination of high-dimensional multiplexed mass cytometry and genetic sequencing, revealed the underlying causes of bleeding in both cases, leading to definitive diagnoses. These cases underscore the potential utility of combined multimodal approaches in evaluating patients with bleeding disorders. Moreover, these high-parameter methods can offer substantial mechanistic insights and can enhance our understanding of the molecular pathogenesis of IPDs. Future studies involving larger patient cohorts are needed to further validate this strategy, directly comparing its diagnostic yield and accuracy with current clinical laboratory testing approaches, which can ultimately improve patient care.
{"title":"Phenotypic and genotypic evaluation of bleeding diagnostic dilemmas: Two case studies","authors":"Sean X. Gu , Ayesha Butt , Vincent P. Schulz , Henry M. Rinder , Alfred I. Lee , Patrick G. Gallagher , John Hwa , Robert D. Bona","doi":"10.1016/j.bcmd.2024.102893","DOIUrl":"10.1016/j.bcmd.2024.102893","url":null,"abstract":"<div><p>Inherited platelet disorders (IPDs) are a heterogeneous group of conditions that present significant challenges in diagnosis and management. Here, we report two cases of patients presenting with clinically significant bleeding but with unclear etiologies by conventional clinical laboratory testing. Further evaluation, utilizing a combination of high-dimensional multiplexed mass cytometry and genetic sequencing, revealed the underlying causes of bleeding in both cases, leading to definitive diagnoses. These cases underscore the potential utility of combined multimodal approaches in evaluating patients with bleeding disorders. Moreover, these high-parameter methods can offer substantial mechanistic insights and can enhance our understanding of the molecular pathogenesis of IPDs. Future studies involving larger patient cohorts are needed to further validate this strategy, directly comparing its diagnostic yield and accuracy with current clinical laboratory testing approaches, which can ultimately improve patient care.</p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"110 ","pages":"Article 102893"},"PeriodicalIF":2.1,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142163317","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}
Pub Date : 2024-09-06DOI: 10.1016/j.bcmd.2024.102886
José Carlos Jaime-Pérez, Mariana González-Treviño, Andrés Gómez-De León, Miguel A. Campos-Bocardo, Renata V. Barragán-Longoria, Olga Graciela Cantú-Rodríguez, César Homero Gutiérrez-Aguirre, David Gómez-Almaguer
{"title":"Corrigendum to “Outpatient ATG-free hematopoietic transplantation for severe aplastic anemia in limited-resource environments offers excellent results: Data from a single LATAM center” [Blood Cells, Mol. Dis. 109 (2024) 102885]","authors":"José Carlos Jaime-Pérez, Mariana González-Treviño, Andrés Gómez-De León, Miguel A. Campos-Bocardo, Renata V. Barragán-Longoria, Olga Graciela Cantú-Rodríguez, César Homero Gutiérrez-Aguirre, David Gómez-Almaguer","doi":"10.1016/j.bcmd.2024.102886","DOIUrl":"10.1016/j.bcmd.2024.102886","url":null,"abstract":"","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"110 ","pages":"Article 102886"},"PeriodicalIF":2.1,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1079979624000640/pdfft?md5=52e69c13f2e3990cdf5b98e200a3ecce&pid=1-s2.0-S1079979624000640-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145049","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}
Pub Date : 2024-08-20DOI: 10.1016/j.bcmd.2024.102885
José Carlos Jaime-Pérez, Mariana González-Treviño, Andrés Gómez-De León, Miguel A. Campos-Bocardo, Renata V. Barragán-Longoria, Olga Graciela Cantú-Rodríguez, César Homero Gutiérrez-Aguirre, David Gómez-Almaguer
Objective
To document the results of outpatient hematopoietic stem cell transplantation (HSCT) from the peripheral blood (PB) of sibling donors without anti-thymocyte globulin (ATG) in the conditioning regimen.
Material and methods
Patients from a low-income population with severe AA who received a PB, unmanipulated sibling HLA-identical HSCT between 2000 and 2020 at a single institution were studied. Survival was the primary outcome.
Results
Forty-one transplants were performed. Time between diagnosis and transplant was five months (1–104). Median age was 37 (range, 4–61) years; 25 (61 %) recipients were males and 32 (78 %) had treatment failure, 9 (22 %) have not received treatment. ATG was administered in 5 (12.2 %) cases; the graft source was PB in 38 (92.7 %) transplants. Twenty-six (63.4 %) transplants were carried out in the outpatient setting. Infections developed in 14 (34.1 %) patients. Primary graft failure (GF) occurred in 3 (7.3 %) patients. The 15-year OS was 81 %, EFS was 77.4 %. Patients with high pre-HSCT transfusion burden had lower OS (p = 0.035) and EFS (p = 0.026). Previous treatment failure and age were not associated with lower OS (p = 0.115, p = 0.069) or EFS (p = 0.088, p = 0.5, respectively).
Conclusions
HLA-identical T-cell replete outpatient HSCT from the PB of sibling donors for AA patients using ATG-free conditioning offers excellent long-term survival.
{"title":"Outpatient ATG-free hematopoietic transplantation for aplastic anemia in limited-resource environments offers excellent results: Data from a single LATAM center","authors":"José Carlos Jaime-Pérez, Mariana González-Treviño, Andrés Gómez-De León, Miguel A. Campos-Bocardo, Renata V. Barragán-Longoria, Olga Graciela Cantú-Rodríguez, César Homero Gutiérrez-Aguirre, David Gómez-Almaguer","doi":"10.1016/j.bcmd.2024.102885","DOIUrl":"10.1016/j.bcmd.2024.102885","url":null,"abstract":"<div><h3>Objective</h3><p>To document the results of outpatient hematopoietic stem cell transplantation (HSCT) from the peripheral blood (PB) of sibling donors without anti-thymocyte globulin (ATG) in the conditioning regimen.</p></div><div><h3>Material and methods</h3><p>Patients from a low-income population with severe AA who received a PB, unmanipulated sibling HLA-identical HSCT between 2000 and 2020 at a single institution were studied. Survival was the primary outcome.</p></div><div><h3>Results</h3><p>Forty-one transplants were performed. Time between diagnosis and transplant was five months (1–104). Median age was 37 (range, 4–61) years; 25 (61 %) recipients were males and 32 (78 %) had treatment failure, 9 (22 %) have not received treatment. ATG was administered in 5 (12.2 %) cases; the graft source was PB in 38 (92.7 %) transplants. Twenty-six (63.4 %) transplants were carried out in the outpatient setting. Infections developed in 14 (34.1 %) patients. Primary graft failure (GF) occurred in 3 (7.3 %) patients. The 15-year OS was 81 %, EFS was 77.4 %. Patients with high pre-HSCT transfusion burden had lower OS (<em>p</em> = 0.035) and EFS (<em>p</em> = 0.026). Previous treatment failure and age were not associated with lower OS (<em>p</em> = 0.115, <em>p</em> = 0.069) or EFS (<em>p</em> = 0.088, <em>p</em> = 0.5, respectively).</p></div><div><h3>Conclusions</h3><p>HLA-identical T-cell replete outpatient HSCT from the PB of sibling donors for AA patients using ATG-free conditioning offers excellent long-term survival.</p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"109 ","pages":"Article 102885"},"PeriodicalIF":2.1,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142049734","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}
Pub Date : 2024-08-14DOI: 10.1016/j.bcmd.2024.102884
Marshall A. Lichtman
The red cell distribution width (RDW) is a standard variable reported in the complete blood count. It has been found to have a consistent relationship to life expectancy in older individuals, prognosis in patients with cardiovascular disease, outcome in those with hematological and non-hematological neoplasms and in a variety of medical circumstances such as non-cardiovascular or cancer related critical illness and postoperative outcome from various procedures. This report reviews some of the key medical publications establishing these relationships with RDW. The precise pathobiological processes that explain the predictive value of the RDW in this wide array of circumstances or why an alteration in erythropoiesis (exaggerated red cell size variation) occurs is uncertain. The possible role of inflammation has been one hypothesis considered, but not established.
{"title":"Red cell distribution width as a bellwether of prognosis","authors":"Marshall A. Lichtman","doi":"10.1016/j.bcmd.2024.102884","DOIUrl":"10.1016/j.bcmd.2024.102884","url":null,"abstract":"<div><p>The red cell distribution width (RDW) is a standard variable reported in the complete blood count. It has been found to have a consistent relationship to life expectancy in older individuals, prognosis in patients with cardiovascular disease, outcome in those with hematological and non-hematological neoplasms and in a variety of medical circumstances such as non-cardiovascular or cancer related critical illness and postoperative outcome from various procedures. This report reviews some of the key medical publications establishing these relationships with RDW. The precise pathobiological processes that explain the predictive value of the RDW in this wide array of circumstances or why an alteration in erythropoiesis (exaggerated red cell size variation) occurs is uncertain. The possible role of inflammation has been one hypothesis considered, but not established.</p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"109 ","pages":"Article 102884"},"PeriodicalIF":2.1,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142012225","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}
Despite several existing laboratory-based studies of hemoglobin (Hb) E (HBB:c.79 G > A)/ β (nucleotide (NT) -28 A > G) (HBB:c.-78 A > G) -thalassemia, no reports have ever provided clinical severity information as well as dependency of blood transfusion. Previously, a comparative study of community- and hospital-recruited Hb E/β-thalassemia subjects was conducted in the lower northern Thailand between June 2020 and December 2021. A mobile medical team visited each community hospital on-site, collecting clinical severity parameters, and conducting Hb and DNA analyses. The control included Hb E/β-thalassemia patients undergoing transfusions. Subgroup study of adult Hb E/β (NT -28 A > G) -thalassemia subjects was subsequently conducted. Additional pediatric individuals were recruited from prenatal diagnosis databases. Twenty adult and nine pediatric subjects were enrolled; all were classified as having mild disease severity. Twenty-two individuals (75.9 %) were asymptomatic. Six adults (20.7 %) required blood transfusion. The mean Hb level of subjects without transfusion (23 [79.3 %]) was 10.77 ± 1.10 g/dL. Hb analysis revealed a distinct EFA pattern with low Hb F fraction. The positive impact of genetic modifiers could not be statistically demonstrated except rs7482144-XmnI. These findings could provide essential information for parents carrying fetuses with Hb E/β (NT -28 A > G) -thalassemia.
尽管现有几项关于血红蛋白（Hb）E（HBB:c.79 G > A）/β（核苷酸（NT）-28 A > G）（HBB:c.-78 A > G）地中海贫血症的实验室研究，但从未有报告提供临床严重程度信息以及输血依赖性。此前，一项针对社区和医院招募的 Hb E/β 地中海贫血症受试者的比较研究于 2020 年 6 月至 2021 年 12 月在泰国北部下游地区进行。一支流动医疗队到各社区医院进行现场访问，收集临床严重程度参数，并进行血红蛋白和 DNA 分析。对照组包括接受输血的 Hb E/β 地中海贫血患者。随后对成年 Hb E/β （NT -28 A > G）地中海贫血患者进行了分组研究。此外，还从产前诊断数据库中招募了其他儿童受试者。共招募了 20 名成人受试者和 9 名儿童受试者；所有受试者均被归类为病情严重程度较轻的患者。22人（75.9%）无症状。六名成人（20.7%）需要输血。没有输血的受试者（23 人 [79.3%]）的平均血红蛋白水平为 10.77 ± 1.10 g/dL。血红蛋白分析显示出明显的 EFA 模式，血红蛋白 F 分数较低。除 rs7482144-XmnI 外，遗传修饰因子的积极影响在统计学上无法证实。这些发现可为怀有 Hb E/β （NT -28 A > G）-地中海贫血胎儿的父母提供重要信息。
{"title":"Clinical characteristics, laboratory features and genetic profile of hemoglobin E (HBB:c.79 G > A)/β (nucleotide -28 A > G) (HBB:c.-78 A > G) -thalassemia subjects identified from community- and hospital-recruited cohorts","authors":"Piyatida Chumnumsiriwath, Prissana Charoenporn, Sawichayaporn Jermnim, Pawanrat Suannum, Monthira Samaisombat, Akamon Tapprom, Rawisut Deoisares, Peerapon Wong","doi":"10.1016/j.bcmd.2024.102883","DOIUrl":"10.1016/j.bcmd.2024.102883","url":null,"abstract":"<div><p>Despite several existing laboratory-based studies of hemoglobin (Hb) E (HBB:c.79 G > A)/ β (nucleotide (NT) -28 A > G) (HBB:c.-78 A > G) -thalassemia, no reports have ever provided clinical severity information as well as dependency of blood transfusion. Previously, a comparative study of community- and hospital-recruited Hb E/β-thalassemia subjects was conducted in the lower northern Thailand between June 2020 and December 2021. A mobile medical team visited each community hospital on-site, collecting clinical severity parameters, and conducting Hb and DNA analyses. The control included Hb E/β-thalassemia patients undergoing transfusions. Subgroup study of adult Hb E/β (NT -28 A > G) -thalassemia subjects was subsequently conducted. Additional pediatric individuals were recruited from prenatal diagnosis databases. Twenty adult and nine pediatric subjects were enrolled; all were classified as having mild disease severity. Twenty-two individuals (75.9 %) were asymptomatic. Six adults (20.7 %) required blood transfusion. The mean Hb level of subjects without transfusion (23 [79.3 %]) was 10.77 ± 1.10 g/dL. Hb analysis revealed a distinct EFA pattern with low Hb F fraction. The positive impact of genetic modifiers could not be statistically demonstrated except rs7482144-<em>Xmn</em>I. These findings could provide essential information for parents carrying fetuses with Hb E/β (NT -28 A > G) -thalassemia.</p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"109 ","pages":"Article 102883"},"PeriodicalIF":2.1,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141997700","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}
Pub Date : 2024-08-02DOI: 10.1016/j.bcmd.2024.102881
Carmen Jacob , Lakeesha Piyasundara , Maria Bonello , Michael Nathan , Stefania Kaninia , Aravinthan Varatharaj , Noémi Roy , Ian Galea
Recent evidence suggests that systemic conditions, particularly those associated with inflammation, can affect erythrocyte deformability in the absence of haematological conditions. In this exploratory study, we investigated the relationship between systemic inflammatory status and erythrocyte deformability (using osmotic gradient ektacytometry) in a heterogenous study population consisting of individuals with no medical concerns, chronic conditions, and acute illness, providing a wide range of systemic inflammation severity.
22 participants were included in a prospective observational study. Maximum Elongation Index (EImax) in ektacytometry served as the readout for erythrocyte deformability. Inflammatory status was assessed using C-reactive protein (CRP) and self-reported symptoms associated with inflammatory activation (Sickness Questionnaire Scores, SicknessQ).
In a univariate linear regression, both CRP and SicknessQ scores significantly predicted EImax (CRP: F(1,20) = 7.751, p < 0.05 (0.011), R2 = 0.279; SicknessQ: F(1,18) = 4.831, p < 0.05 (0.041), R2 = 0.212). Sensitivity analyses with multivariable linear regression correcting for age showed concordant findings.
Results suggest a linear relationship between erythrocyte deformability and biochemical and clinical markers of systemic inflammation. Replication of findings in a larger study, and mechanisms and clinical consequences need further in investigation.
{"title":"Erythrocyte deformability correlates with systemic inflammation","authors":"Carmen Jacob , Lakeesha Piyasundara , Maria Bonello , Michael Nathan , Stefania Kaninia , Aravinthan Varatharaj , Noémi Roy , Ian Galea","doi":"10.1016/j.bcmd.2024.102881","DOIUrl":"10.1016/j.bcmd.2024.102881","url":null,"abstract":"<div><p>Recent evidence suggests that systemic conditions, particularly those associated with inflammation, can affect erythrocyte deformability in the absence of haematological conditions. In this exploratory study, we investigated the relationship between systemic inflammatory status and erythrocyte deformability (using osmotic gradient ektacytometry) in a heterogenous study population consisting of individuals with no medical concerns, chronic conditions, and acute illness, providing a wide range of systemic inflammation severity.</p><p>22 participants were included in a prospective observational study. Maximum Elongation Index (EI<sub>max</sub>) in ektacytometry served as the readout for erythrocyte deformability. Inflammatory status was assessed using C-reactive protein (CRP) and self-reported symptoms associated with inflammatory activation (Sickness Questionnaire Scores, SicknessQ).</p><p>In a univariate linear regression, both CRP and SicknessQ scores significantly predicted EI<sub>max</sub> (CRP: F(1,20) = 7.751, <em>p</em> < 0.05 (0.011), R<sup>2</sup> = 0.279; SicknessQ: F(1,18) = 4.831, p < 0.05 (0.041), R<sup>2</sup> = 0.212). Sensitivity analyses with multivariable linear regression correcting for age showed concordant findings.</p><p>Results suggest a linear relationship between erythrocyte deformability and biochemical and clinical markers of systemic inflammation. Replication of findings in a larger study, and mechanisms and clinical consequences need further in investigation.</p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"109 ","pages":"Article 102881"},"PeriodicalIF":2.1,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1079979624000597/pdfft?md5=f23be722aa973fc8705021ee36b6de01&pid=1-s2.0-S1079979624000597-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141991059","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}
Telomere length related studies are limited in pediatric marrow failure cases due to difficulty in establishing population specific age related normograms. Moreover, there is paucity of data related to clinical relevance of telomere length in idiopathic aplastic anemia (IAA) and non telomere biology inherited bone marrow failure syndrome (IBMFS) cases. Methodology: Hence, in current study we investigated Relative telomere length (RTL) by RQ-PCR in 83 samples as: healthy controls (n = 44), IAA (n = 15) and IBMFS (n = 24). In addition, we performed chromosomal breakage studies and targeted NGS to screen for pathogenic variants. Results & Conclusion: Median RTL was significantly different between control vs. IBMFS (p-0.002), IAA vs. IBMFS (p-0.0075) and DC vs. non-DC IBMFS (p-0.011) but not between control vs. IAA (p-0.46). RTL analysis had clinical utility in differentiating BMF cases as 75 % (9/12) of DC had short/very short telomeres compared to only 17 % (2/12) of non-DC IBMFS, 7 % (1/15) of IAA and 7 % (3/44) of controls (p < 0.001).
{"title":"Clinical utility of relative telomere length analysis in pediatric bone marrow failure","authors":"Shilpa Amatya , Prateek Bhatia , Sudhanshi Raina , Sreejesh Sreedharanunni , Minu Singh , Emine Rahman , M.V. Archana , Amita Trehan","doi":"10.1016/j.bcmd.2024.102882","DOIUrl":"10.1016/j.bcmd.2024.102882","url":null,"abstract":"<div><h3>Introduction</h3><p>Telomere length related studies are limited in pediatric marrow failure cases due to difficulty in establishing population specific age related normograms. Moreover, there is paucity of data related to clinical relevance of telomere length in idiopathic aplastic anemia (IAA) and non telomere biology inherited bone marrow failure syndrome (IBMFS) cases. Methodology: Hence, in current study we investigated Relative telomere length (RTL) by RQ-PCR in 83 samples as: healthy controls (<em>n</em> = 44), IAA (<em>n</em> = 15) and IBMFS (<em>n</em> = 24). In addition, we performed chromosomal breakage studies and targeted NGS to screen for pathogenic variants. Results & Conclusion: Median RTL was significantly different between control vs. IBMFS (<em>p</em>-0.002), IAA vs. IBMFS (<em>p</em>-0.0075) and DC vs. non-DC IBMFS (<em>p</em>-0.011) but not between control vs. IAA (<em>p</em>-0.46). RTL analysis had clinical utility in differentiating BMF cases as 75 % (9/12) of DC had short/very short telomeres compared to only 17 % (2/12) of non-DC IBMFS, 7 % (1/15) of IAA and 7 % (3/44) of controls (<em>p</em> < 0.001).</p></div>","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"109 ","pages":"Article 102882"},"PeriodicalIF":2.1,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888457","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}
Pub Date : 2024-07-19DOI: 10.1016/j.bcmd.2024.102854
Marshall A. Lichtman
<div><p>The journal <em>Blood Cells</em> was initiated in 1975 by Marcel Bessis, a French hematologist and cell biologist, as a vehicle for the publication of papers and discussions presented at an international blood club meeting he convened at L' Institut de Pathologie Cellulaire on the campus of Hôpital Bicétre in Kremlin Bicétre, France, a commune on the southern border of Paris. The group met at the Institute for the first time in October 1972. After the first meeting, Bessis published the articles describing the presentations in the <em>Nouvelle Revue d'Hématologie Française</em>, France's principal journal for articles on the science and practice of hematology of which he was the editor. The refusal of the <em>Nouvelle Revue d'Hématologie Française</em> to continue publishing the papers from the meeting of the blood club in English prompted Bessis to start a new journal, <em>Blood Cells</em>, in 1975. <em>Blood Cells</em>, also, began to accept individual submitted papers unrelated to the blood club meeting and, thus, it evolved into a standard journal. A decade later, when Bessis became ill, he asked Brian Bull, a hematopathologist and professor at Loma Linda University School of Medicine in California to assume the position as the second editor-in-chief. He and Bessis had become scientific collaborators and good friends in the preceding years. In 1995, Ernest Beutler, Chair of Molecular and Experimental Medicine at Scripps Research Institute, assumed the editor-in-chief position and transformed the <em>Journal</em> by making three consequential changes. He expanded its title to <em>Blood Cells, Molecules and Diseases</em>, converted its editorial board to past presidents of the American Society of Hematology plus a few additional experimental hematologists of note, a few from abroad, and he converted the <em>Journal</em> to a digital format, hosted on the Scripps Research Institute server. The <em>Journal</em> was the first published solely in a digital format. It, subsequently, was bought by Academic Press, then Harcourt and, then, by Elsevier. The next three editors-in-chief were (i) Marshall A. Lichtman, then Professor of Medicine (Hematology) and of Biochemistry and Biophysics and former Dean of the School of Medicine and Dentistry at the University of Rochester Medical Center, editor from 2000 to 2013, (ii) Mohandas Narla, then Vice President for Research and Director of The Laboratory of Red Cell Physiology at the New York Blood Center, editor from 2014 to 2021 and (iii) Lionel Blanc, Professor of Molecular Medicine and Pediatrics, Center for Autoimmune, Musculoskeletal and Hematopoietic Diseases, Institute of Molecular Medicine, The Feinstein Institutes for Medical Research and the Les Nelkin Professor of Pediatric Oncology Donald and Barbara Zucker School of Medicine at Hofstra-Northwell from 2022 to the present. Although the <em>Journal</em> publishes papers on any aspect of hematology, it has developed a focus on disorders of r
1975年，法国血液学和细胞生物学家马塞尔-贝西斯（Marcel Bessis）在法国巴黎南部边境的克姆林比塞特尔市比塞特尔医院（Hôpital Bicétre）校园内的细胞病理研究所（L' Institut de Pathologie Cellulaire）召开了一次国际血液俱乐部会议，会上发表的论文和进行的讨论成为《血细胞》杂志的载体。该小组于 1972 年 10 月在研究所举行了第一次会议。第一次会议后，贝西斯在《法国血液学新评论》（Nouvelle Revue d'Hématologie Française）上发表了介绍会议情况的文章。由于《法国新血液学杂志》拒绝继续用英文发表血液俱乐部会议的论文，贝西斯于 1975 年创办了一份新杂志《血细胞》。血细胞》也开始接受个人提交的与血液俱乐部会议无关的论文，并由此发展成为一份标准期刊。十年后，贝西斯病逝，他邀请加州洛马琳达大学医学院教授、血液病理学家布莱恩-布尔担任第二任主编。此前几年，他和贝西斯已成为科研合作者和好朋友。1995 年，斯克里普斯研究所分子与实验医学主席欧内斯特-比尤特勒就任主编一职，并对期刊进行了三项重大改革。他将期刊名称改为《血细胞、分子和疾病》，将编委会成员改为美国血液学会前任主席以及其他几位著名的实验血液学家，其中有几位来自国外，并将期刊转换为数字格式，托管在斯克里普斯研究所的服务器上。该期刊是第一本完全以数字格式出版的期刊。随后，它先后被学术出版社、哈科特出版社和爱思唯尔出版社收购。接下来的三位主编分别是：(i) Marshall A.Lichtman，时任罗切斯特大学医学中心医学（血液学）和生物化学与生物物理学教授，医学与牙科学院前院长，2000 年至 2013 年的编辑；(ii) Mohandas Narla，时任纽约血液中心研究副总裁兼红细胞生理学实验室主任，2014 年至 2021 年的编辑；以及(iii) R. M. B. M. M. M. M、2014年至2021年担任编辑，(iii) 2022年至今担任编辑的是Lionel Blanc，他是费恩斯坦医学研究所分子医学研究所自身免疫、肌肉骨骼和造血疾病中心的分子医学和儿科教授，以及霍夫斯特拉-诺斯韦尔大学唐纳德和芭芭拉-扎克医学院儿科肿瘤学Les Nelkin教授。尽管该杂志发表的论文涉及血液学的方方面面，但它已将重点放在红细胞、红细胞生成和造血功能紊乱方面。2024 年 10 月，《血液学杂志》将迎来创刊 50 周年。
{"title":"The 50th anniversary of Blood Cells, Molecules and Diseases, 1975–2024","authors":"Marshall A. Lichtman","doi":"10.1016/j.bcmd.2024.102854","DOIUrl":"10.1016/j.bcmd.2024.102854","url":null,"abstract":"<div><p>The journal <em>Blood Cells</em> was initiated in 1975 by Marcel Bessis, a French hematologist and cell biologist, as a vehicle for the publication of papers and discussions presented at an international blood club meeting he convened at L' Institut de Pathologie Cellulaire on the campus of Hôpital Bicétre in Kremlin Bicétre, France, a commune on the southern border of Paris. The group met at the Institute for the first time in October 1972. After the first meeting, Bessis published the articles describing the presentations in the <em>Nouvelle Revue d'Hématologie Française</em>, France's principal journal for articles on the science and practice of hematology of which he was the editor. The refusal of the <em>Nouvelle Revue d'Hématologie Française</em> to continue publishing the papers from the meeting of the blood club in English prompted Bessis to start a new journal, <em>Blood Cells</em>, in 1975. <em>Blood Cells</em>, also, began to accept individual submitted papers unrelated to the blood club meeting and, thus, it evolved into a standard journal. A decade later, when Bessis became ill, he asked Brian Bull, a hematopathologist and professor at Loma Linda University School of Medicine in California to assume the position as the second editor-in-chief. He and Bessis had become scientific collaborators and good friends in the preceding years. In 1995, Ernest Beutler, Chair of Molecular and Experimental Medicine at Scripps Research Institute, assumed the editor-in-chief position and transformed the <em>Journal</em> by making three consequential changes. He expanded its title to <em>Blood Cells, Molecules and Diseases</em>, converted its editorial board to past presidents of the American Society of Hematology plus a few additional experimental hematologists of note, a few from abroad, and he converted the <em>Journal</em> to a digital format, hosted on the Scripps Research Institute server. The <em>Journal</em> was the first published solely in a digital format. It, subsequently, was bought by Academic Press, then Harcourt and, then, by Elsevier. The next three editors-in-chief were (i) Marshall A. Lichtman, then Professor of Medicine (Hematology) and of Biochemistry and Biophysics and former Dean of the School of Medicine and Dentistry at the University of Rochester Medical Center, editor from 2000 to 2013, (ii) Mohandas Narla, then Vice President for Research and Director of The Laboratory of Red Cell Physiology at the New York Blood Center, editor from 2014 to 2021 and (iii) Lionel Blanc, Professor of Molecular Medicine and Pediatrics, Center for Autoimmune, Musculoskeletal and Hematopoietic Diseases, Institute of Molecular Medicine, The Feinstein Institutes for Medical Research and the Les Nelkin Professor of Pediatric Oncology Donald and Barbara Zucker School of Medicine at Hofstra-Northwell from 2022 to the present. Although the <em>Journal</em> publishes papers on any aspect of hematology, it has developed a focus on disorders of r","PeriodicalId":8972,"journal":{"name":"Blood Cells Molecules and Diseases","volume":"108 ","pages":"Article 102854"},"PeriodicalIF":2.1,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141729243","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}
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