Pub Date : 2024-10-22DOI: 10.1038/s41375-024-02443-z
H. Jiang, C. Acharya, G. An, M. Zhong, X. Feng, L. Wang, N. Dasilva, Z. Song, G. Yang, F. Adrian, L. Qiu, P. Richardson, N. C. Munshi, Y. -T. Tai, K. C. Anderson
{"title":"Retraction Note: SAR650984 directly induces multiple myeloma cell death via lysosomal-associated and apoptotic pathways, which is further enhanced by pomalidomide","authors":"H. Jiang, C. Acharya, G. An, M. Zhong, X. Feng, L. Wang, N. Dasilva, Z. Song, G. Yang, F. Adrian, L. Qiu, P. Richardson, N. C. Munshi, Y. -T. Tai, K. C. Anderson","doi":"10.1038/s41375-024-02443-z","DOIUrl":"10.1038/s41375-024-02443-z","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"38 12","pages":"2739-2739"},"PeriodicalIF":12.8,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41375-024-02443-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142503170","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 : 2024-10-18DOI: 10.1038/s41375-024-02431-3
Clarissa Corinaldesi, Antony B. Holmes, Gaia Martire, Anna Tosato, Domenico Rizzato, Federica Lovisa, Ilaria Gallingani, Qiong Shen, Lavinia Ferrone, Marian Harris, Kimberly Davies, Luca Molinaro, Umberto Mortara, Angelo Paolo Dei Tos, Kenneth Ofori, Emanuele S. G. D’Amore, Roberto Chiarle, Bo Ngan, Elisa Carraro, Marta Pillon, Shafinaz Hussein, Govind Bhagat, Marco Pizzi, Lara Mussolin, Katia Basso
Burkitt lymphoma (BL) is the most frequent B-cell lymphoma in pediatric patients. While most patients are cured, a fraction of them are resistant to therapy. To investigate BL heterogeneity and the features distinguishing therapy responders (R) from non-responders (NR), we analyzed by single-cell (sc)-transcriptomics diagnostic EBV-negative BL specimens. Analysis of the non-tumor component revealed a predominance of immune cells and a small representation of fibroblasts, enriched in NR. Tumors displayed patient-specific features, as well as shared subpopulations that expressed transcripts related to cell cycle, signaling pathways and cell-of-origin signatures. Several transcripts were differentially expressed in R versus NR. The top candidate, Tropomyosin 2 (TPM2), a member of the tropomyosin actin filament binding protein family, was confirmed to be significantly higher in NR both at the transcript and protein level. Stratification of patients based on TPM2 expression at diagnosis significantly correlated with prognosis, independently of TP53 mutations. These results indicate that BL displays transcriptional heterogeneity and identify candidate biomarkers of therapy resistance.
伯基特淋巴瘤（BL）是儿童患者中最常见的 B 细胞淋巴瘤。虽然大多数患者都能治愈，但也有一部分患者对治疗产生耐药性。为了研究布基特淋巴瘤的异质性以及区分治疗应答者（R）和非应答者（NR）的特征，我们通过单细胞（sc）转录组学分析了诊断性EBV阴性布基特淋巴瘤标本。对非肿瘤成分的分析表明，免疫细胞占主导地位，成纤维细胞占少数，在 NR 中富集。肿瘤显示出患者特异性特征，以及表达与细胞周期、信号通路和原发细胞特征相关转录本的共有亚群。有几个转录本在 R 和 NR 中表达不同。最重要的候选转录本--肌球蛋白肌动蛋白丝结合蛋白家族成员之一的肌球蛋白 2 (TPM2)在 NR 中的转录本和蛋白水平均显著升高。根据诊断时 TPM2 的表达对患者进行分层与预后密切相关，与 TP53 突变无关。这些结果表明BL具有转录异质性，并确定了耐药性的候选生物标志物。
{"title":"Single-cell transcriptomics of pediatric Burkitt lymphoma reveals intra-tumor heterogeneity and markers of therapy resistance","authors":"Clarissa Corinaldesi, Antony B. Holmes, Gaia Martire, Anna Tosato, Domenico Rizzato, Federica Lovisa, Ilaria Gallingani, Qiong Shen, Lavinia Ferrone, Marian Harris, Kimberly Davies, Luca Molinaro, Umberto Mortara, Angelo Paolo Dei Tos, Kenneth Ofori, Emanuele S. G. D’Amore, Roberto Chiarle, Bo Ngan, Elisa Carraro, Marta Pillon, Shafinaz Hussein, Govind Bhagat, Marco Pizzi, Lara Mussolin, Katia Basso","doi":"10.1038/s41375-024-02431-3","DOIUrl":"10.1038/s41375-024-02431-3","url":null,"abstract":"Burkitt lymphoma (BL) is the most frequent B-cell lymphoma in pediatric patients. While most patients are cured, a fraction of them are resistant to therapy. To investigate BL heterogeneity and the features distinguishing therapy responders (R) from non-responders (NR), we analyzed by single-cell (sc)-transcriptomics diagnostic EBV-negative BL specimens. Analysis of the non-tumor component revealed a predominance of immune cells and a small representation of fibroblasts, enriched in NR. Tumors displayed patient-specific features, as well as shared subpopulations that expressed transcripts related to cell cycle, signaling pathways and cell-of-origin signatures. Several transcripts were differentially expressed in R versus NR. The top candidate, Tropomyosin 2 (TPM2), a member of the tropomyosin actin filament binding protein family, was confirmed to be significantly higher in NR both at the transcript and protein level. Stratification of patients based on TPM2 expression at diagnosis significantly correlated with prognosis, independently of TP53 mutations. These results indicate that BL displays transcriptional heterogeneity and identify candidate biomarkers of therapy resistance.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 1","pages":"189-198"},"PeriodicalIF":12.8,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41375-024-02431-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142449249","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}
Genetic alterations are the cornerstone of risk stratification in B-cell precursor acute lymphoblastic leukemia (BCP-ALL), and their accurate identification is critical for optimal treatment. Most cases with ABL-class fusion are classified as high-risk yet display good responses to tyrosine kinase inhibitors (TKIs). Current clinical protocols recommend adding a TKI to chemotherapy as soon as possible, making it mandatory to rapidly identify these alterations. We investigated here whether the identification of immunophenotypic features associated with these molecular alterations could be a valuable screening tool. CD36 expression was shown to be a characteristic feature of ABL- or JAK-class kinase fusions. The main genetic subgroups clustering in the subset with Philadelphia (Ph)-like features were also found to display specific immunophenotypic characteristics. A predictive multiparameter scoring system was generated, segregating genetic subtypes with aberrant kinase activation (PAX5/CRLF2alt, BCR::ABL1, ABL/JAK-class). The most robust markers identified were the TSLPR with CD19/22/9/38/81/304 and CD49f. As TKI adjunction is currently limited to the ABL-class kinase fusions, immunophenotypes distinguishing ABL from JAK-class were also investigated. The flow cytometry method reported here, accessible to most hematology departments, is thus a new useful tool to quickly screen for Ph-like kinase fusion with a good sensitivity (95%) and specificity (96%).
基因改变是 B 细胞前体急性淋巴细胞白血病（BCP-ALL）风险分层的基石，准确识别基因改变对优化治疗至关重要。大多数 ABL 级融合病例被列为高危病例，但对酪氨酸激酶抑制剂（TKIs）的反应良好。目前的临床方案建议尽快在化疗中加入 TKI，因此必须快速识别这些改变。我们在此研究了与这些分子改变相关的免疫表型特征的识别是否可以成为一种有价值的筛选工具。结果显示，CD36的表达是ABL-或JAK-类激酶融合的一个特征。研究还发现，具有费城（Ph）样特征的主要基因亚群也显示出特定的免疫表型特征。该研究生成了一个预测性多参数评分系统，可分离出具有异常激酶激活（PAX5/CRLF2alt、BCR::ABL1、ABL/JAK-class）的基因亚型。确定的最可靠标记是 TSLPR 与 CD19/22/9/38/81/304 和 CD49f。由于 TKI 连接目前仅限于 ABL 类激酶融合，因此还研究了区分 ABL 和 JAK 类的免疫表型。本文报告的流式细胞术方法大多数血液科都能使用，因此是快速筛查类Ph激酶融合的一种新的有用工具，具有良好的灵敏度（95%）和特异性（96%）。
{"title":"CD36 cell surface expression as a surrogate marker to identify ABL/JAK-class kinase fusions in pediatric BCP-ALL","authors":"Marion Strullu, Aurélie Caye-Eude, Elie Robert, Jean-Marie Renard, Amandine Chaye, Julie Galimand, Odile Fenneteau, Chloé Arfeuille, Wendy Cuccuini, Alexandre Theron, Sandrine Thouvenin, Catherine Paillard, Arnaud Petit, Pierre-Simon Rohrlich, Hélène Cavé, André Baruchel, Elodie Lainey","doi":"10.1038/s41375-024-02421-5","DOIUrl":"10.1038/s41375-024-02421-5","url":null,"abstract":"Genetic alterations are the cornerstone of risk stratification in B-cell precursor acute lymphoblastic leukemia (BCP-ALL), and their accurate identification is critical for optimal treatment. Most cases with ABL-class fusion are classified as high-risk yet display good responses to tyrosine kinase inhibitors (TKIs). Current clinical protocols recommend adding a TKI to chemotherapy as soon as possible, making it mandatory to rapidly identify these alterations. We investigated here whether the identification of immunophenotypic features associated with these molecular alterations could be a valuable screening tool. CD36 expression was shown to be a characteristic feature of ABL- or JAK-class kinase fusions. The main genetic subgroups clustering in the subset with Philadelphia (Ph)-like features were also found to display specific immunophenotypic characteristics. A predictive multiparameter scoring system was generated, segregating genetic subtypes with aberrant kinase activation (PAX5/CRLF2alt, BCR::ABL1, ABL/JAK-class). The most robust markers identified were the TSLPR with CD19/22/9/38/81/304 and CD49f. As TKI adjunction is currently limited to the ABL-class kinase fusions, immunophenotypes distinguishing ABL from JAK-class were also investigated. The flow cytometry method reported here, accessible to most hematology departments, is thus a new useful tool to quickly screen for Ph-like kinase fusion with a good sensitivity (95%) and specificity (96%).","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 1","pages":"64-74"},"PeriodicalIF":12.8,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41375-024-02421-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142448262","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 : 2024-10-15DOI: 10.1038/s41375-024-02437-x
Chenwei Yang, Yixin Hu, Li Gao, Zhiheng Li, Yongping Zhang, Ran Zhuo, Yayun Du, Hu Liu, Qi Ji, Minyuan Liu, Jian Pan, Jun Lu, Peifang Xiao, Yuanyuan Tian, Sudan He, Jing Ling, Shaoyan Hu
Acute myeloid leukemia (AML) is an invasive hematopoietic malignancy requiring novel treatment strategies. In this study, we identified phosphodiesterase 3 A (PDE3A) as a potential new target for drug repositioning in AML. PDE3A was preferentially overexpressed in AML cells than in normal cells, and high expression of PDE3A was correlated with lower event-free survival (EFS) in de novo AML patients. The PDE3A inhibitor anagrelide (ANA) profoundly suppresses the proliferation of high PDE3A-expressing AML cells while exhibiting minimal impact on those with low PDE3A expression. Moreover, synergistic effect of ANA with other chemotherapeutic drugs in high PDE3A expression AML cells was observed. The ANA-idarubicin (IDA) combination showed the most remarkable synergistic effect among all ANA-chemotherapeutic drugs commonly used in AML cell line models. Mechanistically, the synergy between ANA and IDA inhibited the survival of PDE3Ahigh AML cell lines through pyroptosis. This mechanism was initiated by GSDME cleavage triggered by caspase-3 activation. In vivo combination treatment of leukemic animals with high PDE3A expression significantly reduced leukemia burden and prolonged survival time compared with single-drug and vehicle control treatments. Our findings suggest that combined ANA and IDA treatment is an innovative and promising therapeutic strategy for AML patients with high PDE3A expression.
急性髓性白血病（AML）是一种需要新型治疗策略的侵袭性造血恶性肿瘤。在这项研究中，我们发现磷酸二酯酶3 A（PDE3A）是治疗急性髓性白血病药物重新定位的潜在新靶点。与正常细胞相比，PDE3A在急性髓细胞白血病细胞中优先过表达，PDE3A的高表达与新发急性髓细胞白血病患者较低的无事件生存期（EFS）相关。PDE3A抑制剂阿那格雷（ANA）能有效抑制PDE3A高表达的AML细胞的增殖，而对PDE3A低表达的细胞影响甚微。此外，在高 PDE3A 表达的 AML 细胞中，还观察到 ANA 与其他化疗药物的协同作用。在所有常用于 AML 细胞系模型的 ANA 化疗药物中，ANA 与idarubicin（IDA）的组合显示出最显著的协同效应。从机理上讲，ANA 和 IDA 的协同作用通过热蛋白沉积抑制了 PDE3A 高的 AML 细胞株的存活。这一机制是由 Caspase-3 激活引发的 GSDME 裂解启动的。与单药和药物对照治疗相比，对高 PDE3A 表达的白血病动物进行体内联合治疗可显著减少白血病负荷并延长存活时间。我们的研究结果表明，对于PDE3A高表达的急性髓细胞白血病患者来说，ANA和IDA联合治疗是一种创新且前景广阔的治疗策略。
{"title":"Anagrelide and idarubicin combination induces GSDME-mediated pyroptosis as a potential therapy for high-PDE3A acute myeloid leukemia","authors":"Chenwei Yang, Yixin Hu, Li Gao, Zhiheng Li, Yongping Zhang, Ran Zhuo, Yayun Du, Hu Liu, Qi Ji, Minyuan Liu, Jian Pan, Jun Lu, Peifang Xiao, Yuanyuan Tian, Sudan He, Jing Ling, Shaoyan Hu","doi":"10.1038/s41375-024-02437-x","DOIUrl":"10.1038/s41375-024-02437-x","url":null,"abstract":"Acute myeloid leukemia (AML) is an invasive hematopoietic malignancy requiring novel treatment strategies. In this study, we identified phosphodiesterase 3 A (PDE3A) as a potential new target for drug repositioning in AML. PDE3A was preferentially overexpressed in AML cells than in normal cells, and high expression of PDE3A was correlated with lower event-free survival (EFS) in de novo AML patients. The PDE3A inhibitor anagrelide (ANA) profoundly suppresses the proliferation of high PDE3A-expressing AML cells while exhibiting minimal impact on those with low PDE3A expression. Moreover, synergistic effect of ANA with other chemotherapeutic drugs in high PDE3A expression AML cells was observed. The ANA-idarubicin (IDA) combination showed the most remarkable synergistic effect among all ANA-chemotherapeutic drugs commonly used in AML cell line models. Mechanistically, the synergy between ANA and IDA inhibited the survival of PDE3Ahigh AML cell lines through pyroptosis. This mechanism was initiated by GSDME cleavage triggered by caspase-3 activation. In vivo combination treatment of leukemic animals with high PDE3A expression significantly reduced leukemia burden and prolonged survival time compared with single-drug and vehicle control treatments. Our findings suggest that combined ANA and IDA treatment is an innovative and promising therapeutic strategy for AML patients with high PDE3A expression.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 1","pages":"98-111"},"PeriodicalIF":12.8,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142440214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-14DOI: 10.1038/s41375-024-02435-z
Jesse M. Tettero, Jacqueline Cloos, Lars Bullinger
{"title":"Acute myeloid leukemia: does sex matter?","authors":"Jesse M. Tettero, Jacqueline Cloos, Lars Bullinger","doi":"10.1038/s41375-024-02435-z","DOIUrl":"10.1038/s41375-024-02435-z","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"38 11","pages":"2329-2331"},"PeriodicalIF":12.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41375-024-02435-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439647","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 : 2024-10-14DOI: 10.1038/s41375-024-02363-y
Hongwei Tang, Huihuang Yan, Suganti Shivaram, Stacey Lehman, Neeraj Sharma, James Smadbeck, Cinthya Zepeda-Mendoza, Shulan Tian, Yan Asmann, Celine Vachon, Alexandre Gaspar Maia, Jonathan Keats, P. Leif Bergsagel, Rafael Fonseca, A. Keith Stewart, Joel-Sean Hsu, Richard K. Kandasamy, Akhilesh Pandey, Marcella A. Kaddoura, Francesco Maura, Amit Mitra, S. Vincent Rajkumar, Shaji K. Kumar, Eran Elhaik, Esteban Braggio, Linda B. Baughn
Multiple myeloma (MM) is a plasma cell (PC) malignancy characterized by cytogenetic abnormalities, such as t(11;14)(q13;q32), resulting in CCND1 overexpression. The rs9344 G allele within CCND1 is the most significant susceptibility allele for t(11;14). Sequencing data from 2 independent cohorts, CoMMpass (n = 698) and Mayo Clinic (n = 661), confirm the positive association between the G allele and t(11;14). Among 80% of individuals heterozygous for rs9344 with t(11;14), the t(11;14) event occurs on the G allele, demonstrating a biological preference for the G allele in t(11;14). Within t(11;14), the G allele is associated with higher CCND1 expression and elevated H3K27ac and H3K4me3. CRISPR/Cas9 mediated A to G conversion resulted in increased H3K27ac over CCND1 and elevated CCND1 expression. ENCODE ChIP-seq data supported a PAX5 binding site within the enhancer region covering rs9344, showing preferential binding to the G allele. Overexpression of PAX5 resulted in increased CCND1 expression. These results support the importance of rs9344 G enhancer in increasing CCND1 expression in MM.
多发性骨髓瘤（MM）是一种浆细胞（PC）恶性肿瘤，其特点是细胞遗传学异常，如 t(11;14)(q13;q32)，导致 CCND1 过度表达。CCND1 中的 rs9344 G 等位基因是 t(11;14)最重要的易感等位基因。来自 CoMMpass（n = 698）和梅奥诊所（n = 661）两个独立队列的测序数据证实了 G 等位基因与 t(11;14)之间的正相关性。在 80% 伴有 t(11;14)的 rs9344 杂合子个体中，t(11;14)事件发生在 G 等位基因上，这表明在 t(11;14)中 G 等位基因具有生物学偏好。在 t(11;14)中，G 等位基因与较高的 CCND1 表达以及较高的 H3K27ac 和 H3K4me3 有关。CRISPR/Cas9 介导的 A 到 G 转换导致 CCND1 上的 H3K27ac 增加和 CCND1 表达升高。ENCODE ChIP-seq 数据支持在覆盖 rs9344 的增强子区域内存在一个 PAX5 结合位点，该位点显示出与 G 等位基因的优先结合。过表达 PAX5 会导致 CCND1 表达增加。这些结果支持了rs9344 G增强子在MM中增加CCND1表达的重要性。
{"title":"Functional variant rs9344 at 11q13.3 regulates CCND1 expression in multiple myeloma with t(11;14)","authors":"Hongwei Tang, Huihuang Yan, Suganti Shivaram, Stacey Lehman, Neeraj Sharma, James Smadbeck, Cinthya Zepeda-Mendoza, Shulan Tian, Yan Asmann, Celine Vachon, Alexandre Gaspar Maia, Jonathan Keats, P. Leif Bergsagel, Rafael Fonseca, A. Keith Stewart, Joel-Sean Hsu, Richard K. Kandasamy, Akhilesh Pandey, Marcella A. Kaddoura, Francesco Maura, Amit Mitra, S. Vincent Rajkumar, Shaji K. Kumar, Eran Elhaik, Esteban Braggio, Linda B. Baughn","doi":"10.1038/s41375-024-02363-y","DOIUrl":"10.1038/s41375-024-02363-y","url":null,"abstract":"Multiple myeloma (MM) is a plasma cell (PC) malignancy characterized by cytogenetic abnormalities, such as t(11;14)(q13;q32), resulting in CCND1 overexpression. The rs9344 G allele within CCND1 is the most significant susceptibility allele for t(11;14). Sequencing data from 2 independent cohorts, CoMMpass (n = 698) and Mayo Clinic (n = 661), confirm the positive association between the G allele and t(11;14). Among 80% of individuals heterozygous for rs9344 with t(11;14), the t(11;14) event occurs on the G allele, demonstrating a biological preference for the G allele in t(11;14). Within t(11;14), the G allele is associated with higher CCND1 expression and elevated H3K27ac and H3K4me3. CRISPR/Cas9 mediated A to G conversion resulted in increased H3K27ac over CCND1 and elevated CCND1 expression. ENCODE ChIP-seq data supported a PAX5 binding site within the enhancer region covering rs9344, showing preferential binding to the G allele. Overexpression of PAX5 resulted in increased CCND1 expression. These results support the importance of rs9344 G enhancer in increasing CCND1 expression in MM.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 1","pages":"42-50"},"PeriodicalIF":12.8,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41375-024-02363-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142431355","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 : 2024-10-09DOI: 10.1038/s41375-024-02384-7
Frederick R. Appelbaum
This invited commentary contains original material that has not been published or submitted elsewhere. Contributions were made by a single author. I have no conflict of interests involving the subject or material.
本特约评论包含未在别处发表或提交的原创材料。本文由一位作者撰写。本人与主题或材料无利益冲突。
{"title":"Offering patients a second chance: what is the minimum cure rate needed to justify allogeneic hematopoietic cell transplantation?","authors":"Frederick R. Appelbaum","doi":"10.1038/s41375-024-02384-7","DOIUrl":"10.1038/s41375-024-02384-7","url":null,"abstract":"This invited commentary contains original material that has not been published or submitted elsewhere. Contributions were made by a single author. I have no conflict of interests involving the subject or material.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"38 12","pages":"2515-2516"},"PeriodicalIF":12.8,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41375-024-02384-7.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142385535","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}
{"title":"ELC52: a novel megakaryocytic leukemia cell line with a CALR type 1 mutation","authors":"Yukiya Yamamoto, Sachiko Iba, Yoko Inaguma, Akinao Okamoto, Akihiro Abe","doi":"10.1038/s41375-024-02434-0","DOIUrl":"10.1038/s41375-024-02434-0","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 1","pages":"234-237"},"PeriodicalIF":12.8,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142385575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The paucity of essential thrombocythemia (ET) and prefibrotic primary myelofibrosis (pre-PMF) in individuals younger than 18 years highlights several unresolved issues in diagnosis, clinical outcomes, and treatment strategies. To address these knowledge gaps, we analyzed a large bidirectional cohort consisting of childhood and adolescent ET (CAA-ET, n = 156) and pre-PMF (CAA-preMF, n = 13), as well as adult ET (n = 349). We introduced immunophenotypic abnormalities as novel clonal markers in CAA-ET and CAA-preMF, establishing a comprehensive method for clonal marker detection that integrated driver and non-driver mutations, positive endogenous erythroid colony formation, immunophenotypic abnormalities, and chromosomal aberrations. Next-generation sequencing revealed distinct mutational profiles between CAA-ET and adult ET, along with different age-related trends in the distribution of driver mutations. Venous thrombosis was more prevalent in CAA-ET, with JAK2 V617F emerging as a potential risk factor (P = 0.018). Immunophenotypic abnormalities were identified as risk factors for disease progression (P = 0.027). Significant differences between expected and actual treatment practices were identified. Compared to CAA-ET, CAA-preMF demonstrated poorer progression-free survival (P < 0.001) and faster disease progression (P = 0.019). This study provides a critical foundation for refining diagnostic, prognostic, and therapeutic approaches for CAA-ET and CAA-preMF.
{"title":"Childhood and adolescent essential thrombocythemia and prefibrotic primary myelofibrosis: insights into diagnosis, outcomes, and treatment from a large Chinese cohort","authors":"Rongfeng Fu, Huan Dong, Wenjing Gu, Ke Meng, Ting Sun, Xiaofan Liu, Xinmiao Qu, Jia Chen, Feng Xue, Wei Liu, Yunfei Chen, Mankai Ju, Xinyue Dai, Ying Chi, Wentian Wang, Xiaolei Pei, Xiaofan Zhu, Renchi Yang, Huiyuan Li, Lei Zhang","doi":"10.1038/s41375-024-02432-2","DOIUrl":"10.1038/s41375-024-02432-2","url":null,"abstract":"The paucity of essential thrombocythemia (ET) and prefibrotic primary myelofibrosis (pre-PMF) in individuals younger than 18 years highlights several unresolved issues in diagnosis, clinical outcomes, and treatment strategies. To address these knowledge gaps, we analyzed a large bidirectional cohort consisting of childhood and adolescent ET (CAA-ET, n = 156) and pre-PMF (CAA-preMF, n = 13), as well as adult ET (n = 349). We introduced immunophenotypic abnormalities as novel clonal markers in CAA-ET and CAA-preMF, establishing a comprehensive method for clonal marker detection that integrated driver and non-driver mutations, positive endogenous erythroid colony formation, immunophenotypic abnormalities, and chromosomal aberrations. Next-generation sequencing revealed distinct mutational profiles between CAA-ET and adult ET, along with different age-related trends in the distribution of driver mutations. Venous thrombosis was more prevalent in CAA-ET, with JAK2 V617F emerging as a potential risk factor (P = 0.018). Immunophenotypic abnormalities were identified as risk factors for disease progression (P = 0.027). Significant differences between expected and actual treatment practices were identified. Compared to CAA-ET, CAA-preMF demonstrated poorer progression-free survival (P < 0.001) and faster disease progression (P = 0.019). This study provides a critical foundation for refining diagnostic, prognostic, and therapeutic approaches for CAA-ET and CAA-preMF.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 1","pages":"155-165"},"PeriodicalIF":12.8,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142384457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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