HemaSphere最新文献

{"title":"Characterization of cancer-associated fibroblasts and their spatial architecture reveals heterogeneity and survival associations in classic Hodgkin lymphoma","authors":"Suvi-Katri Leivonen,&nbsp;Kristiina Karihtala,&nbsp;Teijo Pellinen,&nbsp;Marja-Liisa Karjalainen-Lindsberg,&nbsp;Tomohiro Aoki,&nbsp;Christian Steidl,&nbsp;Sirpa Leppä","doi":"10.1002/hem3.70145","DOIUrl":"https://doi.org/10.1002/hem3.70145","url":null,"abstract":"<p>Cancer-associated fibroblasts (CAFs) are a heterogeneous population of stromal cells, which modulate the immune system and can have both pro- and anti-tumorigenic effects. In classic Hodgkin lymphoma (cHL), the role of CAFs has remained largely undefined. We applied multiplexed immunofluorescence imaging and spatial analysis on tumor samples from two independent cHL patient cohorts (<i>n</i> = 131 and <i>n</i> = 148) to study CAFs and their interactions with Hodgkin Reed–Sternberg (HRS) and tumor microenvironment (TME) cells at the single-cell resolution. We show that higher proportions of CAFs are associated with favorable outcomes, independent of the clinical covariables. In contrast, a subset of CD45⁺ immune cells with strong fibroblast-activation protein positivity, classified as macrophages, was less abundant in nodular sclerosis subtype and associated with worse outcomes. Neighborhood analysis allowed for the identification of colocalization or regional exclusion of phenotypically defined cell types and recurrent cellular neighborhoods. Despite the positive impact of CAF proportions on survival, patients with enrichment of platelet-derived growth factor receptor beta (PDGFRB)-positive CAFs in the vicinity of HRS cells had worse survival in both cohorts, independent of the clinical determinants. Our findings distinguish various subsets of CAFs and macrophages impacting survival in cHL and underscore the importance of the spatial arrangements in the TME.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 5","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70145","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144140620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antigen selection reflected in the subclonal architecture of the B-cell receptor immunoglobulin gene repertoire in splenic marginal zone lymphoma","authors":"Laura Zaragoza-Infante,&nbsp;Andreas Agathangelidis,&nbsp;Anastasia Iatrou,&nbsp;Valentin Junet,&nbsp;Nikos Pechlivanis,&nbsp;Maria Karypidou,&nbsp;Triantafyllia Koletsa,&nbsp;Giorgos Karakatsoulis,&nbsp;Alessio Bruscaggin,&nbsp;Zadie Davis,&nbsp;Valeria Spina,&nbsp;Aurelie Verney,&nbsp;Eleftheria Polychronidou,&nbsp;Fotis Psomopoulos,&nbsp;David Oscier,&nbsp;Alexandra Traverse-Glehen,&nbsp;Maria Papaioannou,&nbsp;Paolo Ghia,&nbsp;Davide Rossi,&nbsp;Anastasia Chatzidimitriou,&nbsp;Kostas Stamatopoulos","doi":"10.1002/hem3.70147","DOIUrl":"https://doi.org/10.1002/hem3.70147","url":null,"abstract":"<p>Almost one-third of all splenic marginal zone lymphoma (SMZL) cases express B-cell receptor immunoglobulin (BcR IG) encoded by the IGHV1-2*04 gene, implicating antigen selection in disease ontogeny. Evidence supporting this notion mostly derives from low-throughput sequencing approaches, which have limitations in capturing the full complexity of the BcR IG gene repertoire. This hinders the comprehensive assessment of the subclonal architecture of SMZL as shaped by antigen selection. To address this, we conducted a high-throughput immunogenetic investigation of SMZL aimed at the comprehensive characterization of the somatic hypermutation (SHM) and intraclonal diversification within the IG genes. We identified significant differences in the SHM and ID profiles between cases expressing the IGHV1-2*04 gene and those expressing other IGHV genes. Specifically, IGHV1-2*04 cases displayed (i) targeted SHM resulting in recurrent replacement SHMs, and (ii) significantly more pronounced intraclonal diversification, reflecting ongoing antigen selection. Overall, our findings suggest that SMZL cases expressing the IGHV1-2*04 gene have a distinct immunogenetic signature shaped by microenvironmental pressure on the clonotypic BcR IG, corroborating the idea that this group may represent a distinct molecular variant of SMZL.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 5","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70147","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144140621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oncogenomic profiling in infant–toddler T-ALL identifies NKX2 family genes as drivers linked to favorable outcomes","authors":"Manon Delafoy,&nbsp;Estelle Balducci,&nbsp;Mathieu Simonin,&nbsp;Antoine Pinton,&nbsp;Guillaume Charbonnier,&nbsp;Lucien Courtois,&nbsp;Ludovic Lhermitte,&nbsp;Camille Gillet,&nbsp;Mélanie Féroul,&nbsp;Aurore Touzart,&nbsp;Agata Cieslak,&nbsp;Charlotte Smith,&nbsp;Marianne Courgeon,&nbsp;Margaux Wiber,&nbsp;Thomas Mercher,&nbsp;Sylvain Latour,&nbsp;Isabelle Arnoux,&nbsp;Paul Saultier,&nbsp;Pierre-Simon Rohrlich,&nbsp;Damien Bodet,&nbsp;Nathalie Grardel,&nbsp;Marion Lubnau,&nbsp;Isabelle Pellier,&nbsp;Sandrine Thouvenin,&nbsp;Nathalie Garnier,&nbsp;Cédric Pastoret,&nbsp;Benoit Brethon,&nbsp;Arnaud Petit,&nbsp;Elizabeth Macintyre,&nbsp;André Baruchel,&nbsp;Vahid Asnafi","doi":"10.1002/hem3.70154","DOIUrl":"https://doi.org/10.1002/hem3.70154","url":null,"abstract":"<p>T-cell acute lymphoblastic leukemia (T-ALL) is a rare and aggressive hematological malignancy primarily affecting adolescents and young adults and is scarce in infants and toddlers under age 3. Unlike B-ALL, T-ALL in this young population remains poorly characterized due to limited data and lacks evidence-based guidelines to help clinicians determine the optimal treatment approach. In this study, we conducted a comprehensive genetic analysis of infant/toddler T-ALL cases from a French national cohort, utilizing high-throughput targeted sequencing, optical genome mapping, and RNA sequencing. Genetic analysis revealed the absence of <i>TLX1/3</i> dysregulation. Instead, we identified a significant prevalence of <i>NKX2</i> rearrangements (<i>n</i> = 9, 33%), co-occurring with <i>MYB</i> alterations (<i>n</i> = 5/9) or chromothripsis-like events (<i>n</i> = 3/9). Additional findings included <i>TAL1/-like</i> anomalies (30%), <i>STAG2::LMO2</i> (15%), <i>ETS</i> rearrangements (15%), and rarely, <i>KMT2A</i> rearrangements (7%). Comparative analyses with 245 patients aged 3–18 years, enrolled in the pediatric FRALLE2000T French protocol, underscored the distinct clinical and genetic profiles of infants/toddlers. Despite presenting with higher rates of hyperleukocytosis and slower responses to treatment, they demonstrated comparable survival outcomes to older pediatric patients, with a 5-year overall survival (OS) rate of 75.4% (95% confidence interval [CI]: 60.0%–94.8%) versus 75.2% (95% CI: 69.8%–81.1%), <i>p</i> = 0.86. Notably, alterations in <i>NKX2</i>, <i>KMT2A</i>, and <i>STAG2::LMO2</i> delineated oncogenic subgroups exhibiting a remarkable 100% OS rate, while patients with <i>TAL1</i> or <i>ETS</i> dysregulation experienced less favorable outcomes. This was further supported by analyses of data from the COG AALL0434 trial, enhancing our understanding of T-ALL in infants/toddlers. Large-scale collaborative studies remain essential to confirm these findings and refine treatment strategies.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 5","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70154","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144140614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic evolution and relapse-associated mutations in adult T-cell acute lymphoblastic leukemia patients treated in PETHEMA trials","authors":"Celia González-Gil,&nbsp;Thaysa Lopes,&nbsp;Mireia Morgades,&nbsp;Francisco Fuster-Tormo,&nbsp;Pau Montesinos,&nbsp;Carlos Rodríguez Medina,&nbsp;Lourdes Hermosín,&nbsp;Teresa González-Martínez,&nbsp;María-Paz Queipo,&nbsp;José González-Campos,&nbsp;Pilar Martínez-Sánchez,&nbsp;Marina Díaz-Beya,&nbsp;Rosa Coll,&nbsp;Clara Maluquer,&nbsp;Lurdes Zamora,&nbsp;Teresa Artola,&nbsp;Ferran Vall-Llovera,&nbsp;Mar Tormo,&nbsp;Anna Torrent,&nbsp;Carolina Martínez-Laperche,&nbsp;Cristina Gil-Cortés,&nbsp;Pere Barba,&nbsp;Marta Cervera,&nbsp;Jordi Ribera,&nbsp;Manuel Fernández-Delgado,&nbsp;Rosa Ayala,&nbsp;Antonia Cladera,&nbsp;María Carmen Mateos,&nbsp;María Jesús Vidal,&nbsp;Jesús Feliu,&nbsp;Ana Torres,&nbsp;Gemma Azaceta,&nbsp;María José Calasanz,&nbsp;Anna Bigas,&nbsp;Manel Esteller,&nbsp;Alberto Orfao,&nbsp;Josep Maria Ribera,&nbsp;Eulalia Genescà","doi":"10.1002/hem3.70148","DOIUrl":"https://doi.org/10.1002/hem3.70148","url":null,"abstract":"<p>Relapse is the main cause of treatment failure in T-cell acute lymphoblastic leukemia (T-ALL). Despite this, data from adult T-ALL patients treated with specific chemotherapeutic regimens that examine predictive markers and describe relapse mechanisms are scarce. In this study, we studied 74 paired diagnosis-relapse samples from 37 patients homogeneously treated with three consecutive measurable residual disease-oriented trials to identify genetic determinants involved in relapse in adult T-ALL. Analysis of single-nucleotide variants and copy number alterations consistently found <i>N/KRAS</i> mutations (20% relapsed cases) at diagnosis and at relapse (resistance profile). <i>N/KRAS</i>^<i>mut</i> patients frequently relapse early during consolidation treatment. Relapse-specific mutations in <i>NT5C2, NR3C1</i>, <i>SMARCA4</i>, and <i>TP53</i> (40% relapse cases) were not detected at diagnosis by conventional molecular techniques (relapse profile). However, single-cell-based analysis revealed a very minor clone containing the NT5C2(p.R367Q) variant at diagnosis. Patients with the NT5C2(p.R367Q) variant mostly relapse later during maintenance treatment. Tracking the <i>NT5C2</i> variant by digital PCR confirm the expansion of the NT5C2 clone at maintenance treatment. Overall, our exploratory analysis suggests a role for these genetic events, most of which have already been described in pediatric cases, driving resistance associated to specific chemotherapeutic agents, contributing to the relapse of a high proportion of adult T-ALL patients (60%).</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 5","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70148","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Applications of machine learning for immunophenotypic measurable residual disease assessment in acute myeloid leukemia","authors":"Tim R. Mocking,&nbsp;Arjan A. van de Loosdrecht,&nbsp;Jacqueline Cloos,&nbsp;Costa Bachas","doi":"10.1002/hem3.70138","DOIUrl":"https://doi.org/10.1002/hem3.70138","url":null,"abstract":"<p>Immunophenotypic detection and quantification of residual leukemic cells by multiparameter flow cytometry is increasingly adopted in the clinical practice of acute myeloid leukemia (AML) to assess measurable residual disease (MRD). However, MRD levels quantified by manual gating analysis can differ based on differences in gating strategy between trained operators and clinical centers. Manual gating requires extensive training, is time-consuming in daily practice, and faces a significant hurdle in analyzing data from next-generation cytometry platforms. To address these challenges, several computational approaches involving machine learning and artificial intelligence algorithms have been proposed to automate or aid the assessment of MRD. However, the immunophenotypic variability between patients and the relatively low proportions of residual leukemic cells in AML challenge most algorithms and require innovative approaches. This review provides an overview of recent efforts in using computational methods for immunophenotypic AML-MRD assessment. We first explain the technical and conceptual background of the different algorithms that have been explored. Next, we discuss their strengths and limitations in the disease-specific context of AML. Finally, we highlight how computational approaches offer a unique opportunity to standardize or even outperform current manual gating analyses, and ultimately, improve the treatment of AML patients.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 5","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70138","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144100936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of CAR T-cell therapy in patients with primary or secondary CNS lymphoma: A study on behalf of the EBMT and the GoCART coalition","authors":"Anna Ossami Saidy,&nbsp;Christophe Peczynski,&nbsp;Catherine Thieblemont,&nbsp;Michael Daskalakis,&nbsp;Marc Wehrli,&nbsp;David Beauvais,&nbsp;Jürgen Finke,&nbsp;Elisabeth Schorb,&nbsp;Peter Vandenberghe,&nbsp;Philipp Berning,&nbsp;Matthias Stelljes,&nbsp;Francis Ayuk,&nbsp;Ron Ram,&nbsp;Malte Von Bonin,&nbsp;Peter Dreger,&nbsp;Wolfgang Bethge,&nbsp;Andrea Kuhnl,&nbsp;Lasse Jost,&nbsp;Friedrich Stölzel,&nbsp;Bastian von Tresckow,&nbsp;Christoph Renner,&nbsp;Stephan Fuhrmann,&nbsp;Jacques-Emmanuelle Galimard,&nbsp;Eva Michel,&nbsp;Ali Bazarbachi,&nbsp;Anna Sureda Balari,&nbsp;Norbert Schmitz,&nbsp;Bertram Glass","doi":"10.1002/hem3.70146","DOIUrl":"https://doi.org/10.1002/hem3.70146","url":null,"abstract":"<p>Patients with relapsed or refractory (r/r) primary central nervous system (CNS) lymphoma (PCNSL) or secondary central nervous system (CNS) lymphoma (SCNSL) face a dismal prognosis. They have been excluded from most clinical CAR T-cell trials as investigators feared an increased risk for severe immune effector cell-associated neurotoxicity (ICANS). To investigate the potential of anti-CD19 CAR T-cell therapy (CART) in such patients, we analyzed data of 100 patients with CNS manifestation treated with CART between January 2018 and July 2023 and reported to European Society for Blood and Marrow Transplantation. Median age was 62 years. Of patients, 58% had failed ≥3 treatment lines, and 40% had received autologous stem-cell transplantation before CART. Fifty-nine patients received axicabtagene ciloleucel, 38 patients were treated with tisagenlecleucel, three patients received other products. At the time of CART, 67 patients had active CNS disease. Overall and progression-free survival (PFS) at 24 months were 37% and 28%. Relapse incidence (RI) at 24 months was 59%, whereas non-relapse mortality at 1 year was 7%. Cytokine release syndrome (CRS) and ICANS of any grade occurred in 83% and 42% of patients, respectively. CRS grade 3 occurred in 11 and ICANS grades 3–4 in 17 patients. Two patients died of neurotoxicity. Elevated lactate dehydrogenase was an independent risk factor for RI and PFS (hazard ratio [HR] 2.4, <i>p</i> = 0.003; HR: 1.9, <i>p</i> = 0.016). Patients with ECOG 2–3 had a significantly increased risk for the development of ICANS (HR 2.68, <i>p</i> = 0.002). These data support the implementation of CART as treatment for patients with r/r PCNSL and SCNSL.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 5","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70146","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144100937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quality of vitamin K antagonist treatment during the last year of life","authors":"Chantal Visser,&nbsp;Eva K. Kempers,&nbsp;Jamilla Goedgebuur,&nbsp;Denise Abbel,&nbsp;Sarah J. Aldridge,&nbsp;Adrian Edwards,&nbsp;Michelle Edwards,&nbsp;Geert-Jan Geersing,&nbsp;Anne Gulbech Ording,&nbsp;Sjef J. C. M. van de Leur,&nbsp;Kate J. Lifford,&nbsp;Isabelle Mahé,&nbsp;Simon P. Mooijaart,&nbsp;Melchior C. Nierman,&nbsp;Johanneke E. A. Portielje,&nbsp;Mette Søgaard,&nbsp;Sebastian Szmit,&nbsp;Nynke M. Wiersma,&nbsp;Simon I. R. Noble,&nbsp;Frederikus A. Klok,&nbsp;Qingui Chen,&nbsp;Suzanne C. Cannegieter,&nbsp;Eric C. T. Geijteman,&nbsp;Marieke J. H. A. Kruip,&nbsp;SERENITY Consortium","doi":"10.1002/hem3.70135","DOIUrl":"https://doi.org/10.1002/hem3.70135","url":null,"abstract":"<p>Limited data exist on the quality of anticoagulation in patients approaching the end of life. This study evaluated vitamin K antagonist (VKA) anticoagulation control during the last year of life, using nationwide data from Statistics Netherlands, linked to anticoagulation clinics' data and the Netherlands Cancer Registry. We included prevalent VKA users who were hospitalized with a severe medical condition and died between January 1, 2013, and December 31, 2019. Anticoagulation control was assessed using time in therapeutic range (TTR), time above therapeutic range (TAR), and time below therapeutic range (TBR) and the international normalized ratio (INR) variance growth rate (VGR), which reflects INR variability. Anticoagulation control was examined by two approaches: (1) over four intervals (0–12 months, 0–9 months, 0–6 months, and 0–3 months preceding death), and (2) in 3-month intervals (9–12, 6–9, 3–6, and 0–3 months before death) to describe temporal changes. Among 6874 VKA users in their last year of life (median age 82 [Interquartile range: 76–87] years, 46.9% female), the most prevalent severe medical conditions were heart disease (60.4%), cancer (16.2%), and hip fracture (15.2%). As death approached, TTR and TBR decreased, while TAR and mean VGR increased, particularly in the last 3 months of life. This decline was more pronounced in cancer patients and acenocoumarol users. In conclusion, the quality of VKA anticoagulation declined in the last year of life in severely ill patients, marked by reduced TTR and increased TAR and VGR, suggesting an increased bleeding risk. These findings highlight the importance of reassessing VKA use and considering discontinuation in patients approaching the end of life.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 5","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70135","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mutational signatures and kataegis in pediatric B-cell precursor acute lymphoblastic leukemia","authors":"Rebeqa Gunnarsson,&nbsp;Minjun Yang,&nbsp;Andrea Biloglav,&nbsp;Kristina B. Lundin-Ström,&nbsp;Henrik Lilljebjörn,&nbsp;Anders Castor,&nbsp;Thoas Fioretos,&nbsp;Linda Olsson-Arvidsson,&nbsp;Kajsa Paulsson,&nbsp;Bertil Johansson","doi":"10.1002/hem3.70136","DOIUrl":"https://doi.org/10.1002/hem3.70136","url":null,"abstract":"&lt;p&gt;Mutational single base substitution (SBS) and insertion/deletion (indel; ID) signatures are characteristic patterns of somatic mutations in cancer that may reflect underlying etiologic factors or pathogenetic mechanisms,&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; for example, deamination of 5-methylcytosine to thymine (SBS1), activity of the APOBEC family of cytidine deaminases (SBS2, SBS13), DNA damage caused by reactive oxygen species (ROS; SBS18), and defects of DNA replication and repair (ID1) (https://cancer.sanger.ac.uk/cosmic/signatures). In recent years, sequencing studies of B-cell precursor acute lymphoblastic leukemias (BCP ALL) have identified SBS signatures of etiological/pathogenetic importance.&lt;span&gt;&lt;sup&gt;2-8&lt;/sup&gt;&lt;/span&gt; However, much remains to be ascertained, such as ID signatures and differences in signatures between major and minor clones.&lt;/p&gt;&lt;p&gt;We performed whole genome sequencing (WGS) of 84 pediatric BCP ALLs with high hyperdiploidy (HeH; &lt;i&gt;n&lt;/i&gt; = 23), &lt;i&gt;ETV6&lt;/i&gt;::&lt;i&gt;RUNX1&lt;/i&gt; (&lt;i&gt;n&lt;/i&gt; = 23), &lt;i&gt;TCF3&lt;/i&gt;::&lt;i&gt;PBX1&lt;/i&gt; (&lt;i&gt;n&lt;/i&gt; = 9), and B-other (&lt;i&gt;n&lt;/i&gt; = 29) to identify SBS/ID signatures and to explore differences between major clones and minor subclones. In addition, WGS and RNA-seq were used to detect fusion genes, single gene rearrangements, single-nucleotide variants (SNVs), indels, expression patterns of gene fusions and gene mutations, and kataegic regions (i.e., localized hypermutations defined by a minimum of at least six mutations with an intermutation distance of ≤1000 bp)&lt;span&gt;&lt;sup&gt;9, 10&lt;/sup&gt;&lt;/span&gt; (Supporting Information and Table S1).&lt;/p&gt;&lt;p&gt;The WGS analysis revealed 230 structural variants (SVs; translocations, inversions, and deletions; Table S2): 105 were in-frame fusions (including all &lt;i&gt;ETV6&lt;/i&gt;::&lt;i&gt;RUNX1&lt;/i&gt; and &lt;i&gt;TCF3&lt;/i&gt;::&lt;i&gt;PBX1&lt;/i&gt; fusions; Figure S1), 52 out-of-frame gene fusions, and 73 single gene rearrangements. In total, 44 novel in-frame gene fusions were identified (e.g., three involving &lt;i&gt;PAX5&lt;/i&gt; fused to &lt;i&gt;MECOM&lt;/i&gt;, &lt;i&gt;RBM39&lt;/i&gt;, and &lt;i&gt;STIM2&lt;/i&gt;, respectively) (Figure S2 and Table S3). As expected, all the &lt;i&gt;ETV6&lt;/i&gt;::&lt;i&gt;RUNX1&lt;/i&gt; and &lt;i&gt;TCF3&lt;/i&gt;::&lt;i&gt;PBX1&lt;/i&gt; fusions were expressed; in contrast, only ~50% of the other in-frame fusions were transcribed, as ascertained by RNA-seq (Supporting Information and Table S2). Of the 104,618 SNVs (median 1082/case) and 1987 indels (median 21/case) identified, 791 (0.8%) SNVs and 74 (3.7%) indels occurred in exonic/splice site regions. The numbers of genomic and exonic/splice site SNVs and indels per case were highly correlated (&lt;i&gt;p&lt;/i&gt; &lt; 0.0001; Figure S3), suggesting that the latter SNVs/indels are random and that many of them are “passengers.” In fact, ~30% of the exonic/splice site SNVs were considered benign by SIFT and PolyPhen, only ~20% of them were expressed, and most (77%) genes targeted by exonic/splice site SNVs/indels were non-recurrent (Table S4). Of the 128 recurrently mutated genes, &lt;i&gt;PAX5&lt;/i&gt;, &lt;i&gt;KRAS&lt;/i&gt;, &lt;i&gt;NRAS, IKZF1&lt;/i&gt;, &lt;i&gt;FLT3","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 5","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70136","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144091315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolism in hematology: Technological advances open new perspectives on disease biology and treatment","authors":"Eileen Haring,&nbsp;Joerg M. Buescher,&nbsp;Petya Apostolova","doi":"10.1002/hem3.70134","DOIUrl":"https://doi.org/10.1002/hem3.70134","url":null,"abstract":"<p>The term metabolism refers to the multi-faceted biochemical reactions within a cell or an organism that occur to maintain energy homeostasis, cell growth, and oxidative balance. Cells possess a high metabolic plasticity, allowing them to adapt to the dynamic requirements of their functional state and environment. Deregulated cellular metabolism is a hallmark of many diseases, including benign and malignant hematological conditions. In the last decade, multiple technological innovations in the metabolism field have made in-depth metabolic analysis broadly applicable. Such studies are shedding new light on normal and malignant hematopoiesis and open avenues to a better understanding of the biology of hematological diseases. In this review, we will first give a brief overview of central metabolic processes. Furthermore, we discuss the most commonly used methods to study metabolism. We begin by elaborating on the use of next-generation sequencing to detect metabolism-related genomic mutations and study transcriptional signatures. Furthermore, we discuss methods for measuring protein expression, such as mass spectrometry (MS), flow cytometry, and cytometry time-of-flight. Next, we describe the use of nuclear magnetic resonance spectroscopy, MS, and flow cytometry for metabolite quantification. Finally, we highlight functional assays to probe metabolic pathways in real-time. We illustrate how these technologies and their combination have advanced our understanding of the role of metabolism. Our goal is to provide hematologists with a comprehensive guide to modern techniques in metabolism research, their benefits and disadvantages, and how they guide our understanding of disease and potentially future personalized therapy decisions.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 5","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70134","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085258","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to Prevalence of type I Gaucher disease in patients with smoldering or multiple myeloma: Results from the prospective, observational CHAGAL study","authors":"","doi":"10.1002/hem3.70142","DOIUrl":"https://doi.org/10.1002/hem3.70142","url":null,"abstract":"<p>Morè S, Federici I, Bossi A, et al. Prevalence of type I Gaucher disease in patients with smoldering or multiple myeloma: results from the prospective, observational CHAGAL study. <i>HemaSphere</i>. 2025;9:e70079. https://doi.org/10.1002/hem3.70079</p><p>In the author listing of the manuscript, the name of an author was incorrectly listed as Tommaso C. De Toritto. The correct name is Tommaso Caravita di Toritto.</p><p>Additionally, the author listing requires further amendment due to an error in the initial manuscript draft. As such, Angela Rago is now included as a co-author.</p><p>The original article has been updated. We apologize for this error.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"9 5","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hem3.70142","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143944606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}