Frontiers in hematology最新文献

{"title":"Effectiveness of biosimilar pegfilgrastim in patients with lymphoma after high-dose chemotherapy and autologous stem cell transplantation: a real-life study","authors":"Barbara Loteta, A. Pitino, Martina Pitea, C. Alati, Giovanni Tripepi, Maria Caterina Micó, Maria Pellicano', Francesca Cogliandro, Gaetana Porto, Giorgia Policastro, Giovanna Utano, Ilaria Maria Delfino, Annalisa Sgarlata, Anna Scopelliti, Aurora Idato, Giovanni Laenza, M. Altomonte, G. D’Arrigo, Mercedes Gori, Massimo Martino","doi":"10.3389/frhem.2024.1441070","DOIUrl":"https://doi.org/10.3389/frhem.2024.1441070","url":null,"abstract":"To evaluate the efficacy of biosimilar (BIO) pegfilgrastim (PEG) in lymphoma patients after autologous stem cell transplantation (ASCT).86 consecutive lymphoma patients who received BIO/PEG after ASCT were assessed. The primary endpoints of this study were the incidence of febrile neutropenia (FN) and time to neutrophil engraftment.Most patients were males (67.4%) with a median age of 48 years. FN occurred in 66 patients (76.7%), and most of the fever was grade 1-2. The median time to neutrophil engraftment was 9 days. The incidence of FN differs based on lymphoma type (p-value <0.01) and was higher in non-Hodgkin lymphoma (NHL) than in Hodgkin Lymphoma (HL). No statistical difference was found between NHL and HL regarding the time to reach the neutrophil engraftment. Hospitalization lasted from a minimum of 9 to a maximum of 34 days. The restricted mean time to discharge was 15.9 days (95%CI 14-16), without differences based on lymphoma type.Although the study has the significant limitation of not being randomized and not having a control arm, it highlights the efficacy and safety of a BIO-PEG formulation in patients with Lymphoma and undergoing ASCT.","PeriodicalId":101407,"journal":{"name":"Frontiers in hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141803738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting the bone marrow niche, moving towards leukemia eradication","authors":"Carla Semedo, Raquel Caroço, António Almeida, Bruno António Cardoso","doi":"10.3389/frhem.2024.1429916","DOIUrl":"https://doi.org/10.3389/frhem.2024.1429916","url":null,"abstract":"Hematopoiesis is a complex and tightly regulated process that drives the formation of mature blood cells from a single hematopoietic stem cell. This complex process occurs within the bone marrow, which, once disrupted or deregulated, subverts normal hematopoietic development, allowing leukemic cells to emerge, proliferate, and thrive. Notably, several cellular populations and paracrine factors within the bone marrow fuel leukemia expansion and progression. This review presents an overview of the main microenvironmental components that promote myeloid leukemia progression, discussing the emerging therapeutical strategies that target both leukemic cells and the supportive bone marrow microenvironment – targeting both the seed and the soil.","PeriodicalId":101407,"journal":{"name":"Frontiers in hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141816344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First clinical experience of isatuximab safety and tolerability in relapsed and refractory multiple myeloma: real-world data from a compassionate use program in Germany","authors":"T. Leitner, Cyrus Khandanpour, K. Wendelin, F. Oduncu, Christoph Kimmich, Ralph Naumann, Miriam Kull, Hartmut Goldschmidt, Martin Ehmer, C. Kiewitz, Hans-Jürgen Salwender","doi":"10.3389/frhem.2024.1335161","DOIUrl":"https://doi.org/10.3389/frhem.2024.1335161","url":null,"abstract":"Therapy for relapsed and refractory multiple myeloma (RRMM) remains challenging. While monoclonal antibodies against CD38 combined with pomalidomide have demonstrated efficacy in clinical trials, real-world data remain sparse. We present real-world data from a compassionate use program (CUP) of isatuximab given in combination with pomalidomide and dexamethasone according to the German Compassionate Use Directive ahead of commercial availability for adult patients with RRMM. Patients had received at least two prior lines of therapy, including lenalidomide and a proteasome inhibitor (PI), and had demonstrated disease progression on the last therapy. Isatuximab was administered as part of the clinical routine. In total, 18 patients were included in the CUP before the official market availability of isatuximab. The data reflect a heterogeneous population in terms of age, risk factors, previous diseases, and treatments. Most of the patients had received two full isatuximab cycles. The analysis showed no new safety signals, supporting the manageable toxicity profile of isatuximab and highlighting its potential in real-world settings.","PeriodicalId":101407,"journal":{"name":"Frontiers in hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141347088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Morphological, clinical, and molecular profiling of post-polycythemia vera accelerated/blast phase occurring with and without antecedent secondary myelofibrosis","authors":"Laura Pelagatti, Giulia Pozzi, Samuele Cortellazzi, Cristina Mancini, Eugenia Martella, L. Pagliaro, Mariateresa Giaimo, Giovanni Roti, M. Vitale, C. Carubbi, E. Masselli","doi":"10.3389/frhem.2024.1356561","DOIUrl":"https://doi.org/10.3389/frhem.2024.1356561","url":null,"abstract":"Polycythemia vera (PV) is a JAK2-mutated myeloproliferative neoplasm (MPN) characterized by clonal erythrocytosis and an intrinsic risk of transformation into acute myeloid leukemia (AML), known as blast-phase (BP) disease, a condition typified by dismal prognosis. In PV, the evolution to BP generally occurs through an overt fibrotic progression, represented by the post-PV myelofibrotic (MF) stage. However, direct leukemic transformation from PV may also occur in up to ~50% of patients. In this study, we sought to shed light on the morphological, clinical, and molecular features that may differentiate BP arising from a direct transition from the PV stage (post-PV-BP) from those evolving through a diagnosis of post-PV myelofibrosis (post-PV-MF-BP). We retrospectively analyzed a cohort of post-PV-BP (n=5) and post-PV-MF-BP (n=5). We found that BP arising from PV directly displayed significantly lower leukocyte count (median 2.93 × 109/L, range: 2.30–39.40 vs. median 41.05 × 109/L, range: 5.46–58.01; P=0.03), and spleen diameter (14.0 cm, range: 11.5–20.0 vs. 25.5 cm, range: 18–26; P=0.03) as compared to those experiencing an overt fibrotic stage. The most striking differences emerged from bone marrow (BM) morphological analysis: all post-PV-BP were characterized by significantly higher cellularity (median 70%, range: 60%–98% vs. 28%, range: 2%–41%, P=0.0245), lower degree of fibrosis (fibrosis grade 1 vs. fibrosis grade 3 in all cases, P=0.008) and dysplastic features involving all three lineages, most prominently the erythroid and megakaryocytic compartment. Next-generation sequencing (NGS) analysis revealed that post-PV-BP cases were enriched in mutations located in genes involved in DNA methylation such as DNMT3A, IDH1/2, and TET2 (45% vs. 15%, P=0.038). With all the limits of the small number of patients for each cohort, our data suggest that BPs that arise directly from PV present a peculiar phenotype, consistent with the molecular signature of the disease, typified by mutations of genes occurring with a high frequency in Myelodysplastic Syndromes (MDS) and MDS/MPN. Further studies in larger cohorts are warranted to translate these observations into robust evidence that may advise therapeutic choices.","PeriodicalId":101407,"journal":{"name":"Frontiers in hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140689422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the effectiveness of COVID-19 vaccines in adults with sickle cell disease during the Omicron period of COVID-19 pandemic","authors":"Kim Abbegail Tan Aldecoa, C. S. Macaraeg, Camelia Arsene, G. Krishnamoorthy, Tiffany Chng, Garrett Cherry, Nabila Chowdhury, Ryan Clark, Dana Deeb, Lisa Deptula, Grey Dietz, Ewomamobuho Eto, Victoria Golston, Landon Lawson, Chioma Mbionwu, Obiefuna Okponyia, Jennifer Orejuela, Thomaidha Qipo, Sumit Raut, Judie Goodman","doi":"10.3389/frhem.2024.1365268","DOIUrl":"https://doi.org/10.3389/frhem.2024.1365268","url":null,"abstract":"The Omicron variant, one of the variants causing the coronavirus disease of 2019 (COVID-19), was first identified in November 2021 and became the predominant variant in 2022. Although causing less severe disease, this variant and its subvariants have been associated with increased transmissibility and limited protection despite vaccination and prior infection. Individuals with sickle cell disease (SCD) are particularly at greater risk of severe illness and death, and studies regarding the effectiveness of COVID-19 vaccination have been limited in this population. The study aims to determine the effectiveness of COVID-19 vaccination during this period among individuals with SCD and to examine various factors that can influence the likelihood of COVID-19 infection and severity among SCD individuals.This is a retrospective analysis of adult patients (≥18 years) with SCD who had emergency and inpatient encounters between January 1 and December 31, 2022. Multivariable regression analysis was performed to determine the effectiveness of the COVID-19 vaccine among this population.The study found that COVID-19 vaccination lowered the infection risk among SCD individuals by over 70% if they have received at least one dose of the vaccine. The study also found that individuals with SCD and a history of acute chest syndrome were over 3 times more likely to have a COVID-19 infection diagnosis than those without a history of acute chest syndrome.The study confirms the effectiveness of the COVID-19 vaccine among individuals with SCD during the Omicron period of the COVID-19 pandemic.","PeriodicalId":101407,"journal":{"name":"Frontiers in hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140723647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Constructing a novel clinical indicator model to predict the occurrence of thalassemia in pregnancy through machine learning algorithm","authors":"Yaoshui Long, Wenxue Bai","doi":"10.3389/frhem.2024.1341225","DOIUrl":"https://doi.org/10.3389/frhem.2024.1341225","url":null,"abstract":"Thalassemia is one of the inherited hemoglobin disorders worldwide, resulting in ineffective erythropoiesis, chronic hemolytic anemia, compensatory hemopoietic expansion, hypercoagulability, etc., and when a mother carries the thalassemia gene, the child is more likely to have severe thalassemia. Furthermore, the economic and time costs of genetic testing for thalassemia prevent many thalassemia patients from being diagnosed in time. To solve this problem, we performed least absolute shrinkage and selection operator (LASSO) regression to analyze the correlation between thalassemia and blood routine indicators containing mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and red blood cell (RBC). We then built a nomogram to predict the occurrence of thalassemia, and receiver operating characteristic (ROC) curve was used to verify the prediction efficiency of this model. In total, we obtained 7,621 cases, including 847 thalassemia patients and 6,774 non-thalassemia. Among the 847 thalassemia patients, with a positivity rate of 67.2%, 569 cases were positive for α-thalassemia, and with a rate of 31.5%, 267 cases were positive for β-thalassemia. The remaining 11 cases were positive for both α- and β-thalassemia. Based on machine learning algorithm, we screened four optimal indicators, namely, MCV, MCH, RBC, and MCHC. The AUC value of MCV, MCH, RBC, and MCHC were 0.907, 0.906, 0.796, and 0.795, respectively. Moreover, the AUC value of the prediction model was 0.911. In summary, a novel and effective machine learning model was built to predict thalassemia, which functioned accurately, and may provide new insights for the early screening of thalassemia in the future.","PeriodicalId":101407,"journal":{"name":"Frontiers in hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140742651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blood pharming: exploring the progress and hurdles in producing in-vitro red blood cells for therapeutic applications","authors":"Hammad Hassan, Sheerien Rajput","doi":"10.3389/frhem.2024.1373408","DOIUrl":"https://doi.org/10.3389/frhem.2024.1373408","url":null,"abstract":"Transfusion Medicine is facing mounting challenges, including but not limited to donor availability, blood supply shortages, and transfusion-associated complications, such as immunogenicity and transmission of viral infections. ‘Blood Pharming’, for in vitro Red Blood Cells (RBC) synthesis, offers a potentially effective approach to addressing the challenges and risks associated with the transfusion of blood and related products. This innovative approach employs cells from variable sources such as Hematopoietic stem cells (HSCs), induced pluripotent stem cells (iPSCs), or immortalized progenitor cell lines, directing their differentiation towards erythropoiesis in an in-vitro environment that mimics the normal bone marrow niche required for erythropoiesis. This review article provides a comprehensive analysis of the progress and hurdles in blood pharming, emphasizing in vitro RBC synthesis for clinical application. In-vitro large-scale production of RBCs offers cutting-edge advantages, such as consistent scalability, the capacity to acquire desired blood phenotypes, and a significant reduction in transfusion-related infections, however, substantial molecular and methodological challenges still need to be addressed before the transfer of this approach from bench to bedside. The review discusses the challenges in ensuring scalability that matches demand and supply, the structural and functional integrity of in-vitro synthesized RBCs compared to their in-vivo counterparts, and the cost-effective methods of RBC synthesis in vitro. It also highlights the importance of implementing thorough characterization and testing protocols to comply with regulatory standards. Additionally, it delves into the ethical concerns associated with commercializing such products. In summary, this review examines the progress and obstacles in the field of in-vitro blood pharming. Through a comprehensive analysis of the present state of the discipline, ongoing scholarly investigations, and prospective avenues of inquiry, our objective is to contribute to a more profound comprehension of the potential impact of synthetic RBCs on the transformation of transfusion medicine.","PeriodicalId":101407,"journal":{"name":"Frontiers in hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140373039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phase II single-arm study of a combination of obinutuzumab and venetoclax in early relapsed or refractory diffuse large B-cell lymphoma—final results of the AGMT NHL15B study","authors":"Ulrich Jaeger, Ingrid Simonitsch-Klupp, Patrick Klammer, A. Egle, S. Heibl, Peter Neumeister, E. Willenbacher, Florian Erlsbacher, J. Larcher-Senn, Philipp B. Staber, E. Porpaczy, C. Skrabs, M. Mayerhoefer, Marcus Hacker, T. Melchardt, Michael A. Fridrik, R. Greil","doi":"10.3389/frhem.2024.1331008","DOIUrl":"https://doi.org/10.3389/frhem.2024.1331008","url":null,"abstract":"Patients with diffuse large B-cell lymphoma (DLBCL) relapsing early (within 12 months) or primary refractory to induction therapy with rituximab (R) and CHOP have a poor prognosis. We therefore initiated a study with obinutuzumab and venetoclax.Twenty-one patients with DLBCL (relapsed within 12 months or primary refractory), detectable Bcl-2 protein expression, and CD20 positivity were included in this prospective single-arm study between 2016 and 2021. Obinutuzumab was administered i.v. at a dose of 1,000 mg on days 1, 8, and 15 in cycle 1 and on day 1 of each of the following 21-day cycles. Venetoclax was given at 800 mg daily p.o. continuously. Treatment was repeated for up to three cycles. Eligible patients were planned to either proceed to cellular therapies or receive up to nine cycles of maintenance. The primary endpoint was objective response rate (ORR) after three cycles (Eudract Nr. 2016-001760-10 and NCT02987400).Twenty-one patients (median age, 64 years) with refractory or early relapsed DLBCL after one (N = 11) to four previous lines of therapy were included. The majority of patients received three cycles of obinutuzumab/venetoclax (range, 1–8). The regimen was well tolerated with manageable cytopenias and infections. Severe adverse events related to treatment were observed in 9.5%. The ORR was 38.1% (8/21 patients) with a best response of five complete remissions (CRs; 23.8%) and three partial remissions (PRs; 14.2%). The primary endpoint (45% ORR) was not met. Response duration was 83.3% at 84 days, with a progression-free survival of 38.8% at 84 days and 25.9% at 168 days and a median overall survival of 169.1 weeks. All deaths were due to underlying disease. Seven patients became eligible for autologous transplant. Overall, nine patients (42.8%) received 11 cellular therapies (5 ASCT and 6 CAR-T). Three patients went directly from obinutuzumab/venetoclax to CAR-T therapy. All patients had successful peripheral stem cell or T-cell harvests. Characteristics of responders include relapsed disease (response rate, 6 of 11 = 54%), very good or good R-IPI (7 of 8), and low number of previous therapies (median = 1).Obinutuzumab/venetoclax represents an effective chemo-free relapse regimen with low toxicity that can be followed by cellular therapies, particularly CAR-T cells.","PeriodicalId":101407,"journal":{"name":"Frontiers in hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140371441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Asymmetric cell division of hematopoietic stem cells: recent advances, emerging concepts, and future perspectives","authors":"Jessica Nunes, Dirk Loeffler","doi":"10.3389/frhem.2024.1373554","DOIUrl":"https://doi.org/10.3389/frhem.2024.1373554","url":null,"abstract":"Hematopoietic stem cells (HSCs) can self-renew and differentiate for the entire life of an organism to produce new blood cells when needed. This process is regulated by asymmetric cell division (ACD), an evolutionarily conserved mechanism whereby cell fate determinants are unequally segregated into the daughter cells during division to instruct different cell fates. After many years of controversy, recent technical advances in microscopy, imaging, and bioinformatics make it now possible to visualize and quantify how factors segregate asymmetrically in dividing HSCs and lead to predictable changes in daughter cell fates many days later. While the molecular processes behind ACD in HSCs are still poorly understood, accumulating evidence suggests that lysosomes and other organelles, including mitochondria, autophagosomes, mitophagosomes, and recycling endosomes can segregate asymmetrically and act as cell fate determinants during divisions. Asymmetric segregation of lysosomes and mitochondria has been shown to predict mitochondrial activity, translation, and differentiation of HSC daughter cells and their offspring. This discovery and recent seminal findings show that lysosomes, once considered to be merely the trash bin of the cell, regulate many aspects of HSC biology and are crucial for the maintenance of quiescence and stem cell function. Here we provide a historical perspective and discuss the recent advances in our understanding of ACD and the role of lysosomes in HSC function. We discuss the limitations of past studies, talk about emerging concepts, and suggest critical next steps required to move the field forward.","PeriodicalId":101407,"journal":{"name":"Frontiers in hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140381226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research and clinical updates on IRAK4 and its roles in inflammation and malignancy: themes and highlights from the 1st symposium on IRAK4 in cancer","authors":"Guillermo Garcia-Manero, Uwe Platzbecker, Kian-Huat Lim, Grzegorz Nowakowski, Omar Abdel-Wahab, Hagop Kantarjian, Amit Verma, D. Starczynowski","doi":"10.3389/frhem.2024.1339870","DOIUrl":"https://doi.org/10.3389/frhem.2024.1339870","url":null,"abstract":"The intracellular serine/threonine interleukin 1 receptor-associated kinase 4 (IRAK4) is necessary for most signaling by activated Toll-like receptors (TLRs). Activation of IRAK4 drives activation of nuclear factor kappa B (NF-κB) and so promotes cell survival, inflammation, and other aspects of the adaptive immune response. However, the IRAK4 pathway can be coopted by cancers and lead to the survival and proliferation of malignant cells. Inappropriate IRAK4 activity has been linked with the progression of myelodysplastic syndrome (MDS), other hematologic malignancies, and some solid tumors, and preclinical cancer models indicate that IRAK4 inhibition has anti-tumor effects. As such, inhibition of IRAK4 is an emerging and attractive target for tumor suppression. The growing interest in IRAK4 motivated the 1st Symposium on IRAK4 in Cancer held in October 2022 to bring together IRAK4 researchers and clinicians to discuss new insights into the biology of IRAK4 and development of IRAK4 inhibitors. Presentations and discussions at the meeting provided updates on the biology of IRAK4 and its links with mutations in the spliceosome, new outcomes from preclinical models that indicate synergy between inhibitors of IRAK4 and FLT3 and BTK inhibitors, and an update on the clinical development of the investigational IRAK4 inhibitor emavusertib, currently being assessed in ongoing phase 1/2 clinical studies in hematologic cancers and several solid tumors.","PeriodicalId":101407,"journal":{"name":"Frontiers in hematology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139775587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}