Pub Date : 2024-11-01DOI: 10.3324/haematol.2024.285545
Lucy C Fox
{"title":"Donor dilemmas in hereditary hematopoietic malignancies.","authors":"Lucy C Fox","doi":"10.3324/haematol.2024.285545","DOIUrl":"10.3324/haematol.2024.285545","url":null,"abstract":"","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11532679/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140944644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.3324/haematol.2024.285445
Arne M De Kreuk
{"title":"Sickle cell and autoimmune disease: a double whammy.","authors":"Arne M De Kreuk","doi":"10.3324/haematol.2024.285445","DOIUrl":"10.3324/haematol.2024.285445","url":null,"abstract":"","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11532681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140944758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.3324/haematol.2024.285242
Guoming Li, Haojie Jiang, Lingbin Wang, Tingting Liang, Chen Ding, Mina Yang, Yingzhi Shen, Min Xin, Lin Zhang, Jing Dai, Xueqing Sun, Xuejiao Chen, Junling Liu, Yanyan Xu
Impaired differentiation of megakaryocytes constitutes the principal etiology of thrombocytopenia. The signal transducer and activator of transcription 3 (STAT3) is a crucial transcription factor in regulating megakaryocyte differentiation, however the precise mechanism of its activation remains unclear. PALLD, an actin-associated protein, has been increasingly recognized for its essential functions in multiple biological processes. This study revealed that megakaryocyte/platelet-specific knockout of Palld in mice exhibited thrombocytopenia due to diminished platelet biogenesis. In megakaryocytes, PALLD deficiency led to impaired proplatelet formation and polyploidization, ultimately weakening their differentiation for platelet production. Mechanistic studies demonstrated that PALLD bound to STAT3 and interacted with its DNA-binding domain and Src homology 2 domain via immunoglobulin domain 3. Moreover, the absence of PALLD attenuated STAT3 Y705 phosphorylation and impeded STAT3 nuclear translocation. Based on the PALLD-STAT3 binding sequence, we designed a peptide C-P3, which can facilitate megakaryocyte differentiation and accelerate platelet production in vivo. In conclusion, this study highlights the pivotal role of PALLD in megakaryocyte differentiation and proposes a novel approach for treating thrombocytopenia by targeting the PALLD-STAT3 interaction.
{"title":"The role of PALLD-STAT3 interaction in megakaryocyte differentiation and thrombocytopenia treatment.","authors":"Guoming Li, Haojie Jiang, Lingbin Wang, Tingting Liang, Chen Ding, Mina Yang, Yingzhi Shen, Min Xin, Lin Zhang, Jing Dai, Xueqing Sun, Xuejiao Chen, Junling Liu, Yanyan Xu","doi":"10.3324/haematol.2024.285242","DOIUrl":"10.3324/haematol.2024.285242","url":null,"abstract":"<p><p>Impaired differentiation of megakaryocytes constitutes the principal etiology of thrombocytopenia. The signal transducer and activator of transcription 3 (STAT3) is a crucial transcription factor in regulating megakaryocyte differentiation, however the precise mechanism of its activation remains unclear. PALLD, an actin-associated protein, has been increasingly recognized for its essential functions in multiple biological processes. This study revealed that megakaryocyte/platelet-specific knockout of Palld in mice exhibited thrombocytopenia due to diminished platelet biogenesis. In megakaryocytes, PALLD deficiency led to impaired proplatelet formation and polyploidization, ultimately weakening their differentiation for platelet production. Mechanistic studies demonstrated that PALLD bound to STAT3 and interacted with its DNA-binding domain and Src homology 2 domain via immunoglobulin domain 3. Moreover, the absence of PALLD attenuated STAT3 Y705 phosphorylation and impeded STAT3 nuclear translocation. Based on the PALLD-STAT3 binding sequence, we designed a peptide C-P3, which can facilitate megakaryocyte differentiation and accelerate platelet production in vivo. In conclusion, this study highlights the pivotal role of PALLD in megakaryocyte differentiation and proposes a novel approach for treating thrombocytopenia by targeting the PALLD-STAT3 interaction.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11532707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141175242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.3324/haematol.2022.282672
Filippo Spriano, Giulio Sartori, Jacopo Sgrignani, Laura Barnabei, Alberto J Arribas, Matilde Guala, Ana Maria Carrasco Del Amor, Meagan R Tomasso, Chiara Tarantelli, Luciano Cascione, Gaetanina Golino, Maria E Riveiro, Roberta Bortolozzi, Antonio Lupia, Francesco Paduano, Samuel Huguet, Keyvan Rezai, Andrea Rinaldi, Francesco Margheriti, Pedro Ventura, Greta Guarda, Giosuè Costa, Roberta Rocca, Alberto Furlan, Luuk M Verdonk, Paolo Innocenti, Nathaniel I Martin, Giampietro Viola, Christoph Driessen, Emanuele Zucca, Anastasios Stathis, Digvijay Gahtory, Maurits Van den Nieuwboer, Beat Bornhauser, Stefano Alcaro, Francesco Trapasso, Susana Cristobal, Shae B Padrick, Natalina Pazzi, Franco Cavalli, Andrea Cavalli, Eugenio Gaudio, Francesco Bertoni
Hematologic cancers are among the most common cancers in adults and children. Despite significant improvements in therapies, many patients still succumb to the disease. Therefore, novel therapies are needed. The Wiskott-Aldrich syndrome protein (WASp) family regulates actin assembly in conjunction with the Arp2/3 complex, a ubiquitous nucleation factor. WASp is expressed exclusively in hematopoietic cells and exists in two allosteric conformations: autoinhibited or activated. Here, we describe the development of EG-011, a first-in-class small molecule activator of the autoinhibited form of WASp. EG-011 possesses in vitro and in vivo antitumor activity as a single agent in lymphoma, leukemia, and multiple myeloma, including models of secondary resistance to PI3K, BTK, and proteasome inhibitors. The in vitro activity was confirmed in a lymphoma xenograft. Actin polymerization and WASp binding were demonstrated using multiple techniques. Transcriptome analysis highlighted homology with drugs inducing actin polymerization.
血液肿瘤是成人和儿童最常见的癌症之一。尽管治疗方法有了很大的改进，但仍有许多患者死于这种疾病。因此，我们需要新的疗法。威斯科特-阿尔德里奇综合征蛋白（WASp）家族与 Arp2/3 复合物（一种无处不在的成核因子）共同调节肌动蛋白的组装。WASp 只在造血细胞中表达，存在两种异构构象：自抑制或激活。在此，我们介绍了 EG-011 的开发情况，它是 WASp 自身抑制型的第一类小分子激活剂。作为一种单药，EG-011 对淋巴瘤、白血病和多发性骨髓瘤具有体外和体内抗肿瘤活性，包括对 PI3K、BTK 和蛋白酶体抑制剂的继发性耐药模型。体外活性在淋巴瘤异种移植中得到了证实。使用多种技术证明了肌动蛋白聚合和 WASp 结合。转录组分析强调了与诱导肌动蛋白聚合的药物的同源性。
{"title":"A first-in-class Wiskott-Aldrich syndrome protein activator with antitumor activity in hematologic cancers.","authors":"Filippo Spriano, Giulio Sartori, Jacopo Sgrignani, Laura Barnabei, Alberto J Arribas, Matilde Guala, Ana Maria Carrasco Del Amor, Meagan R Tomasso, Chiara Tarantelli, Luciano Cascione, Gaetanina Golino, Maria E Riveiro, Roberta Bortolozzi, Antonio Lupia, Francesco Paduano, Samuel Huguet, Keyvan Rezai, Andrea Rinaldi, Francesco Margheriti, Pedro Ventura, Greta Guarda, Giosuè Costa, Roberta Rocca, Alberto Furlan, Luuk M Verdonk, Paolo Innocenti, Nathaniel I Martin, Giampietro Viola, Christoph Driessen, Emanuele Zucca, Anastasios Stathis, Digvijay Gahtory, Maurits Van den Nieuwboer, Beat Bornhauser, Stefano Alcaro, Francesco Trapasso, Susana Cristobal, Shae B Padrick, Natalina Pazzi, Franco Cavalli, Andrea Cavalli, Eugenio Gaudio, Francesco Bertoni","doi":"10.3324/haematol.2022.282672","DOIUrl":"10.3324/haematol.2022.282672","url":null,"abstract":"<p><p>Hematologic cancers are among the most common cancers in adults and children. Despite significant improvements in therapies, many patients still succumb to the disease. Therefore, novel therapies are needed. The Wiskott-Aldrich syndrome protein (WASp) family regulates actin assembly in conjunction with the Arp2/3 complex, a ubiquitous nucleation factor. WASp is expressed exclusively in hematopoietic cells and exists in two allosteric conformations: autoinhibited or activated. Here, we describe the development of EG-011, a first-in-class small molecule activator of the autoinhibited form of WASp. EG-011 possesses in vitro and in vivo antitumor activity as a single agent in lymphoma, leukemia, and multiple myeloma, including models of secondary resistance to PI3K, BTK, and proteasome inhibitors. The in vitro activity was confirmed in a lymphoma xenograft. Actin polymerization and WASp binding were demonstrated using multiple techniques. Transcriptome analysis highlighted homology with drugs inducing actin polymerization.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11532693/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141426730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.3324/haematol.2023.284786
Charles Herbaux, Caroline Bret, Emmanuel Bachy, Pierre Bories, Roberta Di Blasi, Alexis Cuffel, Thomas Gastinne, Thierry Lamy, Mikael Roussel, Krimo Bouabdallah, David Beauvais, Guillaume Cartron, Jacques-Olivier Bay, Didier Blaise, Marie-Therese Rubio, Mohamad Mohty, Fabien Le Bras, Olivier Casasnovas, Julien Guy, Stephanie Guidez, Cristina Castilla Llorente, Olivier Hermine, Laurianne Drieu La Rochelle, Sylvain Carras, Blandine Guffroy, Sophie Caillat-Zucman, Roch Houot, Steven Le Gouill
{"title":"Brexucabtagene autoleucel in relapsed or refractory mantle cell lymphoma, intention-to-treat use in the DESCAR-T registry.","authors":"Charles Herbaux, Caroline Bret, Emmanuel Bachy, Pierre Bories, Roberta Di Blasi, Alexis Cuffel, Thomas Gastinne, Thierry Lamy, Mikael Roussel, Krimo Bouabdallah, David Beauvais, Guillaume Cartron, Jacques-Olivier Bay, Didier Blaise, Marie-Therese Rubio, Mohamad Mohty, Fabien Le Bras, Olivier Casasnovas, Julien Guy, Stephanie Guidez, Cristina Castilla Llorente, Olivier Hermine, Laurianne Drieu La Rochelle, Sylvain Carras, Blandine Guffroy, Sophie Caillat-Zucman, Roch Houot, Steven Le Gouill","doi":"10.3324/haematol.2023.284786","DOIUrl":"10.3324/haematol.2023.284786","url":null,"abstract":"","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11532701/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141426732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.3324/haematol.2024.285650
Armin Rashidi, Lang Liang, Ted Gooley, Philippe P Hujoel, Alex Zevin, Marilynn Rothen, Mary K Hagstrom, Corey Cutler, Stephanie J Lee, David R Dean, Hervé Y Sroussi, Nathaniel S Treister
{"title":"Microbiota signature of oral chronic graft-<I>versus</I>-host disease 6+ years after transplantation.","authors":"Armin Rashidi, Lang Liang, Ted Gooley, Philippe P Hujoel, Alex Zevin, Marilynn Rothen, Mary K Hagstrom, Corey Cutler, Stephanie J Lee, David R Dean, Hervé Y Sroussi, Nathaniel S Treister","doi":"10.3324/haematol.2024.285650","DOIUrl":"10.3324/haematol.2024.285650","url":null,"abstract":"","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11532723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141579540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.3324/haematol.2024.285809
Atieh Modarresi, Claire L Shovlin
{"title":"Integration of genotypic data into clinical trial design and reporting in hereditary hemorrhagic telangiectasia could help personalize treatment.","authors":"Atieh Modarresi, Claire L Shovlin","doi":"10.3324/haematol.2024.285809","DOIUrl":"10.3324/haematol.2024.285809","url":null,"abstract":"","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11532719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141456370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-01DOI: 10.3324/haematol.2024.285170
A Vera De Jonge, Wassilis S C Bruins, Carolien Duetz, Charlotte L B M Korst, Rosa Rentenaar, Meliha Cosovic, Merve Eken, Marie-Jose Kersten, Yorick Sandberg, Rozemarijn S Van Rijn, Rob Fijnheer, Pim Mutsaers, Vibeke K J Vergote, Djamila Issa, Aart Beeker, Yavuz M Bilgin, Otto Visser, Erik Van Werkhoven, Margaretha G M Roemer, Martine E D Chamuleau, Tuna Mutis
{"title":"Response to DA-EPOCH-R is associated with activation of 'fitter' cytotoxic T cells in patients with newly diagnosed double and triple hit high-grade B-cell lymphoma.","authors":"A Vera De Jonge, Wassilis S C Bruins, Carolien Duetz, Charlotte L B M Korst, Rosa Rentenaar, Meliha Cosovic, Merve Eken, Marie-Jose Kersten, Yorick Sandberg, Rozemarijn S Van Rijn, Rob Fijnheer, Pim Mutsaers, Vibeke K J Vergote, Djamila Issa, Aart Beeker, Yavuz M Bilgin, Otto Visser, Erik Van Werkhoven, Margaretha G M Roemer, Martine E D Chamuleau, Tuna Mutis","doi":"10.3324/haematol.2024.285170","DOIUrl":"10.3324/haematol.2024.285170","url":null,"abstract":"","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11532709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141497899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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