EJHaem最新文献

{"title":"Life-Threatening Cytopenias in a Jehovah's Witness Following CD19-Directed Chimeric Antigen Receptor T Cell Therapy","authors":"Corinne J. Shamehdi,&nbsp;Christian A. Gordillo,&nbsp;Ahmed Sawas,&nbsp;Rodney Macedo,&nbsp;Markus Y. Mapara,&nbsp;Ran Reshef","doi":"10.1002/jha2.70119","DOIUrl":"https://doi.org/10.1002/jha2.70119","url":null,"abstract":"<p>Here we report on a Jehovah's Witness (JW) patient who experienced profound and prolonged life-threatening cytopenias following CD19-targeted CAR T cell therapy, successfully managed with bloodless medicine strategies. This case highlights the potential risks of CAR T therapy, even in patients without known hematotoxicity risk factors. By implementing tailored bloodless strategies, the patient received CAR T therapy without significant infectious, cardiac, or bleeding complications. Remarkably, they remain in remission 5 years later with normal blood counts. This underscores the viability of CAR T cell therapy for JW patients, emphasizing the importance of careful patient selection and risk-benefit deliberation. Further research into severe cytopenias post-CAR T therapy is critically needed.</p><p><b>Trial Registration</b>: The authors have confirmed clinical trial registration is not needed for this submission.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 4","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70119","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144832569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted Degradation of Class 1 HDACs With PROTACs is Highly Effective at Inducing DLBCL Cell Death","authors":"Abdullah Alraddadi,&nbsp;Joshua P. Smalley,&nbsp;Wael Alzahrani,&nbsp;Anes Saleh,&nbsp;Fares Al-Mansour,&nbsp;Buwei He,&nbsp;Thong H. Cao,&nbsp;Sandrine Jayne,&nbsp;Martin Dyer,&nbsp;James T. Hodgkinson,&nbsp;Donald J. L. Jones,&nbsp;Shaun M. Cowley,&nbsp;Salvador Macip","doi":"10.1002/jha2.70127","DOIUrl":"https://doi.org/10.1002/jha2.70127","url":null,"abstract":"<p>Despite the good options for the management of Diffuse large B-cell lymphoma (DLBCL), a significant percentage of patients either do not respond to current treatments or relapse after a short time. Thus, a wider palette of targeted therapeutic strategies is needed. Histone deacetylases (HDACs) inhibitors have shown promising responses in B-cell malignancies, but their off-target effects limit their efficiency. Here, we investigated the use of novel targeted therapeutics against class I HDACs to specifically induce cell death in DLBCL cells. We show that a proteolysis targeting chimera (PROTAC) that combined HDAC inhibitor CI-994 and an IAP ligand had a strong effect in killing different DLBCL cell lines, being more effective in doing so than CI-994 on its own. Moreover, we show that this was concomitant with the induction of DNA damage and apoptosis. A proteomics screen showed that the mechanism of induction of cell death by this PROTAC likely depends on the simultaneous activation of pro-apoptotic proteins (such as PARP-1, PDCD6IP, DAPk1, TP53BP1, and CACYBP) and the inhibition of pro-survival pathways. We conclude that eliminating class I HDACs with specific PROTACs could be an effective and precise strategy for treating DLBCL that should be further tested for their potential clinical relevance.</p><p><b>Trial Registration</b>: The authors have confirmed clinical trial registration is not needed for this submission.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 4","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70127","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144832816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Pilot Collaborative Study to Improve the Diagnosis and Treatment of Patients With Newly Diagnosed Diffuse Large B-Cell Lymphoma in Senegal: The LYMPHODAK Study","authors":"Saliou Diop,&nbsp;Charline Moulin,&nbsp;Sokhna Aïssatou Touré,&nbsp;Serigne Mourtalla Gueye,&nbsp;Sabine Deltour,&nbsp;Yankhoba Diop,&nbsp;Fatou Samba Ndiaye,&nbsp;Mouhamadou Cherif Dial,&nbsp;Hervé Sartelet,&nbsp;Moussa Seck,&nbsp;Seynabou Fall,&nbsp;Alioune Badara Senghor,&nbsp;Awa Oumar Touré,&nbsp;Blaise Felix Faye,&nbsp;Elimane Seydi Bousso,&nbsp;Alioune Badara Diallo,&nbsp;Mohamed Keita,&nbsp;Elhadji Daouda Niang,&nbsp;Nata Dieng,&nbsp;Jean Vigneron,&nbsp;Catherine Thieblemont,&nbsp;Vincent Lévy,&nbsp;Martine Raphael,&nbsp;Pierre Feugier","doi":"10.1002/jha2.70133","DOIUrl":"https://doi.org/10.1002/jha2.70133","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Management of diffuse large B-cell lymphoma (DLBCL) in Africa is hampered by limited access to diagnosis and treatment, due to the small number of haematopathologists and lack of clear healthcare pathway. A cooperation between France and Senegal was established to improve diagnosis and provide access to the standard-of-care (R-CHOP) to patients with DLBCL in Dakar.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Surgical biopsies were examined in Senegal, then through the Internet Pathology Suite platform, and, when needed, further studied in France. A diagnosis was thus reached for 65/70 biopsies from adults with suspected lymphoma, including 31 DLBCL. A total of 30 patients entered a pilot treatment of six cures of R-CHOP, follow-up and support therapy, between July 2018 and May 2022. The overall response rate was 73% with 57% of complete responses. With a median follow-up of 11.4 months, 24-month overall and progression-free survival rates are of 80% (95% CI 58–91) and 74% (95% CI 50–88). Grade 3/4 haematological toxicity was reported in 20% of the cases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study brings the proof-of-concept that an accurate DLBCL diagnosis can be obtained in Senegal with organized support and that R-CHOP therapy can be properly conducted, yielding the expected efficacy with acceptable safety.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial Registration</h3>\u0000 \u0000 <p>SEN18/11</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 4","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70133","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144832817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine Learning Algorithm to Explore Patients With Heterogeneous Treatment Effects of Clinically Significant CMV Infection and Non-Relapse Mortality After HSCT.","authors":"Takashi Toya, Yujiro Nakajima, Konan Hara, Satoshi Kaito, Tetsuya Nishida, Naoyuki Uchida, Naoki Shingai, Wataru Takeda, Yukiyasu Ozawa, Masatsugu Tanaka, Satoshi Yoshihara, Yuta Katayama, Tetsuya Eto, Masashi Sawa, Shuichi Ota, Hiroyuki Ohigashi, Satoru Takada, Keisuke Kataoka, Junya Kanda, Takahiro Fukuda, Masao Ogata, Ayumi Taguchi, Yoshiko Atsuta","doi":"10.1002/jha2.70117","DOIUrl":"10.1002/jha2.70117","url":null,"abstract":"<p><strong>Introduction: </strong>Clinically significant cytomegalovirus infection (csCMVi) and non-relapse mortality (NRM) remain serious concerns after allogeneic hematopoietic stem cell transplantation (HSCT), but subpopulations with heterogeneous treatment effects (HTEs) is unclear. Although machine learning (ML) algorithms have recently been applied to HSCT, the methodology has not been well elucidated.</p><p><strong>Methods: </strong>We developed a ML algorithm which combined weighting procedures and left-truncated and right-censored trees based on classification and regression tree algorithms to fit survival data with time-varying covariates and competing risks comprehensively. The Japanese large-scale registry data were applied to the algorithm to explore subpopulations with HTEs of csCMVi and NRM after HSCT. Its performance was evaluated by comparing their c-indices with those of the conventional Fine-Gray model.</p><p><strong>Results: </strong>A total of 10,480 patients were divided into training (75%) and test (25%) cohorts; the training cohort was used to develop the ML model. Using the model, patient CMV-seropositivity, patient age, and acute graft-versus-host disease were identified as important predictors of csCMVi. In addition, the patients were successfully classified by the estimated cumulative incidence of csCMVi, which varied from 22.7% at 0.5 year to 82.7%. This model also depicts interpretable survival trees in various settings. Similarly, the patients can be also classified based on the estimated 3-year NRM, which varied from 8.0% to 48.5%. C-indices of the ML and the Fine-Gray model using the test cohort showed comparable performance.</p><p><strong>Conclusion: </strong>A reliable, explainable, and interpretable ML model was developed to explore subpopulations with HTEs of csCMVi and NRM after HSCT. <b>Trial Registration</b>: The authors have confirmed clinical trial registration is not needed for this submission.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 4","pages":"e70117"},"PeriodicalIF":1.2,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12335206/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144818453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Successful Allogeneic Stem Cell Transplant for Philadelphia Chromosome Negative Acute Lymphoblastic Leukemia After Pneumonectomy for Pulmonary Mucormycosis: A Case Report and Review of the Literature.","authors":"Alexander O'Hara, Sanja Zepcan, Stephanie Tsai, Imran Puthawala, Jorgena Kosti-Schwartz","doi":"10.1002/jha2.70125","DOIUrl":"10.1002/jha2.70125","url":null,"abstract":"<p><p>The incidence of relapsed Philadelphia chromosome-negative acute lymphoblastic leukemia in adults is estimated to be 40%-50%. Allogeneic stem cell transplantation can improve survival in relapsed acute lymphoblastic leukemia; however, impaired pulmonary function is detrimental for surviving the transplantation process. Here, we present a successful case of allogeneic transplantation for relapsed B-acute lymphoblastic leukemia after total resection of the left lung due to angioinvasive pulmonary mucormycosis. To our knowledge, this is the first successful case of allogeneic transplantation after total pneumonectomy. Specific considerations in this case included careful donor selection, judicious choice of pre-transplantation conditioning regimen, and utilizing novel immunotherapies to ensure major residual disease negativity prior to transplant. It is our hope that this case provides additional guidance to clinicians caring for patients with hematologic malignancies who develop invasive fungal infections and require major lung surgeries.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 4","pages":"e70125"},"PeriodicalIF":1.2,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12335202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144818454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decitabine-Driven Foetal Haemoglobin Induction in Townes Mice and Human Erythroblasts","authors":"Ariadna Carol Illa,&nbsp;Desmond Wai Loon Chin,&nbsp;Martha Clark,&nbsp;Jesper Petersen,&nbsp;Søren Skov,&nbsp;Andreas Glenthøj,&nbsp;Carsten Dan Ley","doi":"10.1002/jha2.70120","DOIUrl":"https://doi.org/10.1002/jha2.70120","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Induction of foetal haemoglobin (HbF) is a clinically validated approach to modulate the severity of sickle cell disease (SCD). This manuscript evaluates the efficacy of decitabine, a DNA methyltransferase (DNMT) inhibitor, in inducing HbF in healthy human erythroblasts and Townes mice, which are well-established systems modelling SCD.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Healthy human erythroblasts were treated with decitabine, and HbF induction was measured. Townes sickle cell mice were administered decitabine for 12 weeks, and various haematological parameters were assessed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>In healthy human erythroblasts, decitabine treatment resulted in a significant increase in the fraction of HbF-rich cells (F-cells), accompanied by elevated HbF protein levels. The HbF induction was superior to that achieved with hydroxyurea, the primary therapy for SCD. In Townes mice, the maximal response was observed after 12 weeks of dosing, with an increase in both HbF protein and F-cells, alongside reduced red blood cell and reticulocyte counts. Additionally, we observed changes in other haematological parameters, such as increased mean corpuscular volume and mean corpuscular haemoglobin. However, the HbF induction observed in the mice was modest relative to known human responses. No marked improvements in SCD-related biomarkers such as haemolysis or liver function were detected, suggesting that the mouse model may not fully capture the extent of phenotype improvement. Histopathological examination revealed no adverse effects on bone marrow cellularity or morphology and indicated a protective effect on liver tissue integrity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our results demonstrate that decitabine induces HbF in a dose-dependent manner in both in vitro and in vivo settings, highlighting the complexity of HbF induction as a treatment for SCD and underscoring the need for further refinement of this model for SCD therapy research.</p>\u0000 \u0000 <p><b>Trial Registration</b>: The authors have confirmed clinical trial registration is not needed for this submission.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 4","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70120","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144773872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive Genetic Analysis of Central Nervous System Involvement in Mycosis Fungoides: A Case Report","authors":"Yasumasa Nakata,&nbsp;Fumihiko Ouchi,&nbsp;Kota Yoshifuji,&nbsp;Daichi Sadato,&nbsp;Kouhei Yamamoto,&nbsp;Yuriko Kawase,&nbsp;Takehiko Mori","doi":"10.1002/jha2.70118","DOIUrl":"https://doi.org/10.1002/jha2.70118","url":null,"abstract":"<p>The incidence of central nervous system (CNS) involvement in mycosis fungoides (MF) is low. Here, we report a case of CNS involvement 3 years after MF diagnosis, comparing genetic alterations identified by amplicon-based targeted sequencing between a primary skin sample and a brain tissue sample. <i>TNFAIP3</i> mutation, <i>MYC</i> gain, <i>CDKN2A</i>/<i>B</i> loss, and <i>SOCS1</i> loss were concordantly detected, while <i>MYC</i> mutation was only found in the brain sample. This is the first report of a comprehensive genetic analysis of CNS involvement in MF, providing novel insights into genetic factors potentially associated with CNS involvement.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 4","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70118","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144751579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic Value of Geriatric Characteristics in Allogeneic Haematopoietic Stem Cell Transplant Recipients Aged Over 60 Years","authors":"Xiu Hue Lee,&nbsp;Chieh Hwee Ang,&nbsp;Tertius Tansloan Tuy,&nbsp;Jeffrey Kim Siang Quek,&nbsp;Hein Than,&nbsp;Francesca Lorraine Wei Inng Lim,&nbsp;Yeow Tee Goh,&nbsp;Yeh Ching Linn,&nbsp;William Ying Khee Hwang,&nbsp;Aloysius Yew Leng Ho,&nbsp;Lawrence Cheng Kiat Ng","doi":"10.1002/jha2.70115","DOIUrl":"https://doi.org/10.1002/jha2.70115","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Allogeneic haematopoietic stem cell transplant (alloHSCT) offers a curative option for older adults with haematological malignancies. The use of geriatric assessments has transformed the landscape of haemato-oncology care by improving risk stratification. We aim to study the prognostic value of geriatric characteristics in patients aged ≥ 60 years who underwent alloHSCT at Singapore General Hospital between 2017 and 2023. Patient data were examined retrospectively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 66 patients were included, with a median age of 65 years and 42% aged above 65. Most patients had acute leukaemia (61%), and stem cell sources included matched sibling donor (18%), matched unrelated donor (33%) and haploidentical donor (48%). Karnofsky Performance Status (KPS) was ≥ 90 in 41% of patients, and 86% had Haematopoietic Cell Transplantation-Comorbidity Index (HCT-CI) scores of 0–2. The median Cumulative Illness Rating Scale-Geriatric (CIRS-G) score was 5. A total of 12% had renal insufficiency.</p>\u0000 \u0000 <p>At a median follow-up of 32.5 months, 2-year non-relapse mortality (NRM), progression-free survival and overall survival (OS) were 21%, 55% and 58%, respectively. On multivariate analysis, age &gt; 65 years (HR 3.84, <i>p</i> = 0.027) and renal insufficiency (HR 6.28, <i>p</i> = 0.005) were associated with increased risks of NRM. Similarly, age &gt; 65 years (HR 2.75, <i>p</i> = 0.03) and renal insufficiency (HR 3.46, <i>p</i> = 0.01) conferred inferior OS. KPS, HCT-CI, CIRS-G, albumin, body mass index and polypharmacy did not predict for NRM and OS.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study supports the feasibility of alloHSCT as a treatment option for older adults with haematological malignancies. Prospective studies incorporating geriatric assessment will allow personalised transplant strategies to improve post-transplant outcomes.</p>\u0000 \u0000 <p><b>Trial Registration</b>: The authors have confirmed clinical trial registration is not needed for this submission</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 4","pages":""},"PeriodicalIF":1.2,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70115","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144751578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapid Identification of DUX4::IGH Fusion in Acute Lymphoblastic Leukemia","authors":"Kyoko Moritani,&nbsp;Minenori Eguchi-Ishimae,&nbsp;Mari Tezuka-Kagajo,&nbsp;Machiko Miyamoto,&nbsp;Mayumi Iwamoto,&nbsp;Sanae Kawakami,&nbsp;Ryota Nakamura,&nbsp;Kozo Nagai,&nbsp;Sawa Tomomatsu,&nbsp;Tsuyoshi Imai,&nbsp;Yasushi Ishida,&nbsp;Hisamichi Tauchi,&nbsp;Eiichi Ishii,&nbsp;Mariko Eguchi","doi":"10.1002/jha2.70099","DOIUrl":"https://doi.org/10.1002/jha2.70099","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p><i>DUX4</i> is rearranged and overexpressed in a subgroup of acute lymphoblastic leukemia (ALL) with B-precursor phenotype, with a favorable outcome. Even though characteristic gene expression signature as well as surface expression of CD2/CD371 could be a hallmark of <i>DUX4</i>-rearranged ALL, actual detection of <i>DUX4</i> rearrangement is, however, largely dependent on whole transcriptome analysis due to the highly repetitive nature of <i>DUX4</i> gene loci and insertion as the main mechanism of fusion gene formation.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Polymerase chain reactions (PCRs) with several combinations of multiplex primers located on <i>DUX4</i> and <i>IGH</i> gene loci were used for the detection of <i>DUX4::IGH</i>, which represents more than 90% of <i>DUX4</i> fusion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p><i>DUX4::IGH</i> fusion was successfully detected in three out of 50 ALL cases analyzed by standard PCR, and these positive cases showed variable insertion of <i>DUX4</i> into the <i>IGH</i> locus. In all patients, sequences of unknown origin were observed at the junction of <i>DUX4</i> and <i>IGH</i> sequences, indicating the role of the V(D)J recombination mechanism in fusion gene formation. Although <i>DUX4</i> is tandemly repeated at its locus, only a single copy of the <i>DUX4</i> sequence was detected at the <i>IGH</i> locus in two of the three <i>DUX4</i>-rearranged ALL cases. As previously reported, both CD2 and CD371 were positive in all cases with <i>DUX4</i>::<i>IGH</i> fusion, suggesting that the combination of CD2 and CD371 could be a more reliable marker for detecting the presence of this fusion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Identification of <i>DUX4</i>::<i>IGH</i> fusion in ALL could be possible more easily by a simple multiplex PCR strategy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70099","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144716648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Intersection of Lynch Syndrome and Hematological Malignancies: A Rare Short Report","authors":"Tomomi Oka,&nbsp;Takeshi Nakajima,&nbsp;Makoto Iwasaki,&nbsp;June Takeda,&nbsp;Masako Torishima,&nbsp;Maki Sakurada,&nbsp;Takuya Shimizu,&nbsp;Takero Shindo,&nbsp;Masakazu Fujimoto,&nbsp;Shinya Otsuki,&nbsp;Hironori Haga,&nbsp;Kokichi Sugano,&nbsp;Miho Ando,&nbsp;Chisaki Mizumoto,&nbsp;Junya Kanda,&nbsp;Yasuhito Nannya,&nbsp;Seishi Ogawa,&nbsp;Akifumi Takaori-Kondo,&nbsp;Shinji Kosugi","doi":"10.1002/jha2.70116","DOIUrl":"https://doi.org/10.1002/jha2.70116","url":null,"abstract":"<p>Lynch syndrome (LS), which is an autosomal dominant disorder caused primarily by germline pathogenic variants of mismatch repair (MMR) genes, cases a number of malignancies. Hematologic malignancies are not included as related tumors of LS because it has not yet been established whether the carcinogenesis of hematologic malignancies is associated with MMR genes.</p><p>A 75-year-old woman was admitted to our hospital with acute myeloid leukemia (AML) that had progressed from myelodysplastic syndrome (MDS). She had a history of multiple myeloma (MM) and multiple tumors associated with LS. Genetic testing revealed extensive homozygous deletions ranging from Exon 9 of <i>EPCAM</i> to Exons 1–6 of <i>MSH2</i>. Finally, we diagnosed her with LS. It revealed that the <i>MSH2</i> homo-deletion occurred in myeloid cells after the onset of MM. Immunohistochemistry for MMR proteins on bone marrow specimens at MDS showed the loss of staining for the MSH2 and MSH6 proteins in myeloid cells. However, microsatellite instability was negative in spite of the large homozygous deletion of <i>MSH2</i>.</p><p>It remains unclear whether the homo-deletion of <i>MSH2</i> is involved in the development of MDS/AML. Future studies are warranted to confirm the impact of MMR variants on the pathogenesis/chemoresistance of myeloid neoplasms.</p><p>Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission.</p>","PeriodicalId":72883,"journal":{"name":"EJHaem","volume":"6 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jha2.70116","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144716974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}