Hematological Oncology最新文献

{"title":"Allogeneic transplantation for adult T-cell leukemia/lymphoma in adolescent and young adults and young patients: A nationwide retrospective study by the ATL working group of the Japan society for transplantation and cellular therapy","authors":"Hidehiro Itonaga,&nbsp;Takuya Fukushima,&nbsp;Koji Kato,&nbsp;Nobuaki Nakano,&nbsp;Takeharu Kato,&nbsp;Takashi Tanaka,&nbsp;Tetsuya Eto,&nbsp;Yasuo Mori,&nbsp;Toshiro Kawakita,&nbsp;Naoyuki Uchida,&nbsp;Machiko Fujioka,&nbsp;Hirohisa Nakamae,&nbsp;Masao Ogata,&nbsp;Satoko Morishima,&nbsp;Takahiro Fukuda,&nbsp;Yoshinobu Kanda,&nbsp;Yoshiko Atsuta,&nbsp;Shigeo Fuji,&nbsp;Makoto Yoshimitsu","doi":"10.1002/hon.3315","DOIUrl":"10.1002/hon.3315","url":null,"abstract":"<p>Allogeneic hematopoietic stem cell transplantation (allo-HSCT) provides durable remission for patients with adult T-cell leukemia/lymphoma (ATL); however, few studies have focused on post-transplant outcomes in ATL patients ≤49 years. To clarify prognostic factors in ATL among patients &lt;40 years (adolescents and young adult [AYA]; <i>n</i> = 73) and 40–49 years (Young; <i>n</i> = 330), we conducted a nationwide retrospective study. Estimated 3-year overall survival (OS) rates were 61.8% and 43.1% in AYA and Young patients, respectively (<i>p</i> = 0.005). In the multivariate analysis, Young patients showed worse OS (Hazard ratio (HR) [95% confidential interval] 1.62 [1.10–2.39], <i>p</i> = 0.015), chronic graft-versus-host disease (GVHD)-free and relapse-free survival (CRFS) (HR 1.54 [1.10–2.14], <i>p</i> = 0.011), and GVHD-free and relapse-free survival (GRFS) (HR 1.40 [1.04–1.88], <i>p</i> = 0.026) than AYA patients. No significant differences were observed in OS, CRFS, or GRFS between the myeloablative conditioning (MAC) and reduced-intensity conditioning (RIC) regimens; however, non-relapse mortality was significantly lower in patients with the RIC regimen than those with the MAC regimen (HR 0.46 [0.24–0.86], <i>p</i> = 0.015). In summary, OS was worse in Young patients than in AYA patients in the allo-HSCT setting for ATL. Furthermore, the RIC regimen has potential as an alternative treatment option for ATL patients ≤49 years.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world data for marginal zone lymphoma patients in the French REALYSA cohort: The REALMA study","authors":"C. Bommier,&nbsp;M. Donzel,&nbsp;C. Rossi,&nbsp;L. M. Fornecker,&nbsp;F. Bijou,&nbsp;A. Chauchet,&nbsp;L. Lebras,&nbsp;L. Ysabaert,&nbsp;C. Haioun,&nbsp;K. Bouabdallah,&nbsp;T. Gastinne,&nbsp;N. Morineau,&nbsp;S. Amorim,&nbsp;F. Jardin,&nbsp;J. Abraham,&nbsp;T. Lamy de la Chapelle,&nbsp;R. Gressin,&nbsp;L. Fouillet,&nbsp;C. Fruchart,&nbsp;G. Olivier,&nbsp;F. Morschhauser,&nbsp;F. Cherblanc,&nbsp;A. Belot,&nbsp;S. Le Guyader,&nbsp;A. Monnereau,&nbsp;H. Ghesquieres,&nbsp;C. Thieblemont","doi":"10.1002/hon.3314","DOIUrl":"10.1002/hon.3314","url":null,"abstract":"<p>Marginal Zone Lymphoma (MZL) comprises three subtypes: extranodal MZL (EMZL), splenic MZL (SMZL) and nodal MZL (NMZL). Since clinical trials have limited representativeness, there is a need for real-world data (RWD) evidence in MZL. Real-world data in Lymphoma and survival in Adults (REALYSA) is a prospective multicentric French cohort of newly diagnosed lymphoma patients. This study consists of the first abstraction of MZL patients prospectively included in REALYSA between 12/2018 and 01/2021 with at least 1 year of follow-up. It provides a landscape description of clinical characteristics, initial workup, quality of life and first-line therapy performed in routine practice. Among 207 included patients, 122 presented with EMZL, 51 with SMZL and 34 with NMZL. At baseline, median age was 67 years (range 28–96), and patients reported a favorable global health status (75/100 (IQR 58,83)) – which was higher in NMZL and lower in SMZL patients (<i>p</i> = 0.006). ¹⁸FDG-PET/CT was frequently performed at initial workup (EMZL 72%, SMZL 73%, NMZL 85%). Active surveillance was the initial management for 58 (28%) patients. The most prescribed therapies were rituximab-chlorambucil in the EMZL population (30%), rituximab monotherapy in the SMZL population (37%) and R-CHOP (24%)/bendamustine-rituximab (15%) in the NMZL population. At end of first line, overall response rate was 93% among treated patients with 75% of complete response. This French nationwide study provided for the first time prospective RWD on clinical characteristics, initial management and treatment response of MZL patients.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.3314","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142345200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterizing second line and beyond therapies for primary central nervous system lymphomas","authors":"Brian Primeaux,&nbsp;Chelsea Luo,&nbsp;Erin K. Yeung,&nbsp;Caitlin Linger,&nbsp;Sheree Chen,&nbsp;Bryan Do","doi":"10.1002/hon.3313","DOIUrl":"10.1002/hon.3313","url":null,"abstract":"<p>Primary central nervous system (CNS) lymphoma (PCNSL) is a rare and aggressive lymphoma that affects the CNS without other systemic involvement. High-dose methotrexate (HDMTX)-based regimens are recommended frontline treatment, followed by consolidation with either high-dose chemotherapy, whole brain radiation (WBRT) +/− sequential temozolomide (TMZ), or autologous stem cell transplant (autoSCT). Despite advancements with HDMTX and rituximab, up to half of patients will relapse. Treatment for relapsed or refractory (R/R) disease varies widely as preferred regimens are not well-established. Our study aimed to provide real-world characterization of R/R PCNSL therapies. The secondary objective was characterization of consolidation methods after frontline treatment. This retrospective, descriptive analysis included 54 adult PCNSL patients that received a HDMTX-based frontline regimen between 4/1/2016 and 7/1/2022. Patients receiving HDMTX for the purpose of secondary CNS lymphoma, non-B cell origin PCNSL, and intraocular lymphoma were excluded. Thirty-one patients (57%) received consolidation therapy with rituximab and high-dose cytarabine (R-HDAC), WBRT, or both. Thirteen patients (24%) proceeded with autoSCT. Twenty-five patients had disease progression, with 17 patients receiving second line treatment. The second line treatments were WBRT (24%), clinical trial (18%), rituximab with lenalidomide (R²; 18%), re-induction with HDMTX-based regimens (18%), ibrutinib with rituximab (12%) and R-HDAC (12%). Seven patients progressed, and all received third line treatment. Treatments varied, including R²; ibrutinib +/− HDMTX; rituximab, methotrexate, and cytarabine; R-HDAC; R-nivolumab; and WBRT. Five patients received a fourth line regimen of R +/− lenalidomide, R-HDMTX, or nivolumab monotherapy. Regimens used for the three patients who received fifth line treatment and beyond included R-TMZ and pembrolizumab monotherapy in addition to previously described regimens. Regimen selection is varied and highly dependent on physician preference and patient factors, including clinical trial eligibility, prior therapies, performance status, organ function, and treatment intent. Prospective clinical trials are needed to guide optimal management.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142345199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Superior prognostic accuracy of FIGO staging system in primary female genital tract lymphomas: A retrospective study (IELSG35)","authors":"Maria Cristina Pirosa,&nbsp;Sara Steffanoni,&nbsp;Anna Vanazzi,&nbsp;Fabiana Esposito,&nbsp;Angela Polino,&nbsp;Alberto Schena,&nbsp;Francesco Landi,&nbsp;Maria Elena Cabrera,&nbsp;Saad Akhtar,&nbsp;Santiago Gardella,&nbsp;Osnat Bairey,&nbsp;Astrid Pavlovsky,&nbsp;Anastasios Stathis,&nbsp;Emanuele Zucca","doi":"10.1002/hon.3312","DOIUrl":"https://doi.org/10.1002/hon.3312","url":null,"abstract":"<p>Primary lymphoma of the female genital tract (PLFGT) is a rare type of extranodal lymphoma. In this retrospective study from the International Extranodal Lymphoma Study Group, we analyzed clinical data from 60 women diagnosed with PLFGT between 1982 and 2012. The median age was 52 years. Limited stage, as defined by the Ann Arbor and FIGO staging systems, was observed in 55% and 63% of cases, respectively. The uterus was the primary site of lymphoma in 25 cases, with the ovaries as the second most common site (<i>n</i> = 24). The most common histological subtype was diffuse large B-cell lymphoma (DLBCL, <i>n</i> = 44), followed by follicular lymphoma and marginal zone lymphoma (6 patients each). Two patients received surgery alone as first-line therapy, while 58 underwent systemic therapy, 16 following major surgery. Thirteen patients received consolidation radiotherapy and six were given central nervous system (CNS) prophylaxis. Twenty patients had disease progression or recurrence. Six patients with DLBCL (14%) experienced CNS relapse, which was the only site of recurrence in five of them. All but one patient with CNS relapse had primary ovarian involvement, and three had bulky disease; none of these patients had received CNS prophylaxis. With a median follow-up of 60 months, the median overall survival of the DLBCL cohort was approximately 13 years, with a 5-year survival rate of 77%. In multivariable analysis, advanced disease according to the FIGO system was the only parameter significantly associated with shorter overall, cause-specific, and progression-free survival in patients with DLBCL.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.3312","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142324507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Direct determination of chronic myeloid leukemia prevalence in Lombardy—Italy: Global implications","authors":"N. Polverelli,&nbsp;M. Anghilieri,&nbsp;C. Elena,&nbsp;T. Intermesoli,&nbsp;E. Pungolino,&nbsp;M. D’Adda,&nbsp;A. Iurlo,&nbsp;M. Maffioli,&nbsp;F. Lunghi,&nbsp;V. Bertolli,&nbsp;N. Orofino,&nbsp;C. Sissa,&nbsp;C. Fiamenghi,&nbsp;A. Gardellini,&nbsp;M. Ubezio,&nbsp;M. C. Carraro,&nbsp;P. Corradini,&nbsp;F. Giglio,&nbsp;M. C. Pasquini,&nbsp;R. Palazzolo,&nbsp;R. Calori,&nbsp;M. Ercolanoni,&nbsp;C. Gambacorti-Passerini","doi":"10.1002/hon.3311","DOIUrl":"https://doi.org/10.1002/hon.3311","url":null,"abstract":"<p>Lombardy represents the largest region of Italy by population, with almost 10 million residents, a dimension similar to a medium size country like Sweden or Belgium. The CML subcommittee of the Lombardy Hematology Network (REL-CML) conducted a study at the beginning of 2023. Prevalence was calculated by direct input from the 21 centers participating in REL-CML. Tyrosine Kinase Inhibitors (TKI) prescription records collected from the ARIA regional registry were used to estimate the number of CML patients followed in smaller centers not participating in REL-CML. A total of 2285 patients were registered, representing a prevalence of 0.23 ‰. These data were compared to a similar census conducted in 2005, at the beginning of the TKI era, where a prevalence of 0.029‰ was calculated. This indicates that an almost 10 times increase took place during this period of time. Imatinib represents the most frequently prescribed first-line TKI; its use in 2022 still represented 75% of total first line prescriptions. An increased concentration of the care of CML patients in specialized REL centers with a decreased dispersion of patients in small centers was also evident over this 18 year period of time. Nineteen % of patients discontinued treatment, highlighting persisting logistical and biological challenges; one some recommendations on CML management are included to this aim.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.3311","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142276632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Secondary acute myeloid leukemia and early infection are independent predictors of poor survival in acute myeloid leukemia treated with hypomethylating agents and venetoclax","authors":"Stefano Cordella,&nbsp;Davide Giusti,&nbsp;Eleonora De Bellis,&nbsp;Michelina Dargenio,&nbsp;Federica Creti’,&nbsp;Davide Lazzarotto,&nbsp;Chiara Cattaneo,&nbsp;Nicola Stefano Fracchiolla,&nbsp;Matteo Piccini,&nbsp;Fabio Forghieri,&nbsp;Livio Pagano,&nbsp;Anna Candoni","doi":"10.1002/hon.3310","DOIUrl":"https://doi.org/10.1002/hon.3310","url":null,"abstract":"","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142234018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treatment-free remission as a new goal in the management of chronic myeloid leukemia: Clinical and biological aspects","authors":"Daniele Cattaneo,&nbsp;Cristina Bucelli,&nbsp;Valentina Bellani,&nbsp;Barbara Mora,&nbsp;Alessandra Iurlo","doi":"10.1002/hon.3309","DOIUrl":"https://doi.org/10.1002/hon.3309","url":null,"abstract":"<p>The therapeutic armamentarium of chronic myeloid leukemia (CML) has dramatically improved after small molecule tyrosine kinase inhibitors (TKIs) targeting <i>BCR::ABL1</i> became available, with a life expectancy now close to that of the general population. Although highly effective, these drugs also have a toxicity profile that is often mild to moderate, but sometimes severe. Indeed, long-term treatment with TKIs can lead to chronic adverse events that can negatively affect patients' quality of life and can promote significant morbidity and mortality, particularly in the case of second- or third-generation TKIs. Treatment discontinuation has therefore become an emerging goal for CML patients and numerous studies have evaluated in off-TKI subjects what requirements are appropriate for an attempt at treatment-free remission (TFR). TFR eligibility is currently limited to a small population of subjects with both deep and sustained molecular responses to TKIs. For those attempting TFR, average success rates are promising, with 25%–30% of patients experiencing prolonged TFR. In case of failure to maintain sustained TFR, safety results to date are reassuring, with almost all patients responding successfully to resumption of TKIs, and advanced-phase disease progression representing a very rare event. The purpose of this review is to discuss guidelines for TKI discontinuation, clinical advances from clinical trials and real-life experiences, and describe areas of research, particularly regarding the biological factors capable of predicting the success of TFR.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142233225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bruton tyrosine kinase inhibitor monotherapy in B-cell lymphoma and risk of infection: A systematic review and meta-analysis of randomized controlled trials","authors":"Mohammed Zuber,&nbsp;Samruddhi Nandkumar Borate,&nbsp;Pooja Gokhale,&nbsp;Akhila Yerubandi,&nbsp;N. M. Mahmudul Alam Bhuiya,&nbsp;Smita Rawal,&nbsp;Henry N. Young,&nbsp;Lorenzo Villa Zapata","doi":"10.1002/hon.3308","DOIUrl":"https://doi.org/10.1002/hon.3308","url":null,"abstract":"<p>Bruton's tyrosine kinase (BTK) inhibitors are important therapeutic advances with promising efficacy outcomes in the treatment of patients with chronic lymphocytic leukemia and other B-cell lymphoma subtypes. However, the utility of BTK inhibitors can be limited by adverse events such as infections. In this systematic review and meta-analysis, we aim to determine the risk of various infections associated with BTK inhibitor monotherapy in B-cell lymphoma patients. A comprehensive search was conducted in MEDLINE/PubMed, Embase, and Web of Science databases from their inception until October 2023. ClinicalTrials.gov, bibliographies, and relevant conference abstracts were also searched for additional records. Randomized controlled trials that included any B-cell lymphoma patients treated with BTK inhibitor monotherapy and reported infection were included. Meta-analysis was performed to calculate risk ratio (RR) using a random-effects model in <i>R</i> Statistical Software, version 4.3.2. Of 3292 studies retrieved, we included 12 studies in this systematic review and meta-analysis. The median age of patients across the study arms ranged between 64 and 73 years. The overall pooled RR for any grade upper respiratory tract infections (URTI) associated with BTK inhibitor treatment was 1.55 (95% Confidence Interval (CI) 1.22–1.97). The RR of grade ≥3 URTI was reported in 14 out of 1046 patients, yielding an RR of 1.46 (95% CI 0.61–3.54), which was not statistically significant. The pooled RR of any grade pneumonia was 1.20 (95% CI 0.68–2.10) and grade ≥3 pneumonia was 1.12 (95% CI 0.67–1.85), both of which were not statistically significant. Patients with B-cell lymphoma who are undergoing BTK inhibitor monotherapy face an elevated risk of developing URTI. Clinicians prescribing BTK inhibitors should be aware of the potential infectious events that may occur. Close monitoring and the implementation of effective prophylactic measures are essential for managing these patients.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.3308","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142231060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research on the mechanism of HOPX-HDAC2 interaction inducing differentiation blockage in acute myeloid leukemia","authors":"Fang He,&nbsp;Yan Tu,&nbsp;Lihong Ni","doi":"10.1002/hon.3307","DOIUrl":"10.1002/hon.3307","url":null,"abstract":"<p>Homeodomain-only protein homeobox (<i>HOPX</i>) mainly exerts its transcriptional repression by physically sequestering the serum co-repressor and recruiting histone deacetylase (<i>HDAC</i>), possessing important potential as a prognostic gene in acute myeloid leukemia (AML). <i>HDACs</i> play crucial roles in cell growth, gene regulation, and metabolism, and they are also important factors in promoting AML progression. Therefore, this project attempts to investigate whether <i>HOPX</i> affects AML progression by interacting with <i>HDAC2</i> protein. Bioinformatics analysis was employed to identify potential prognostic genes in AML. Flow cytometry and MTT assays were performed to analyze the cellular biological functions of the AML prognostic marker <i>HOPX</i>. The interaction network of <i>HOPX</i> was analyzed using the Search Tool for the Retrieval of Interacting Genes database, and the interaction between <i>HOPX</i> and <i>HDAC2</i> was observed using endogenous and exogenous immunoprecipitation. <i>HOPX</i> is highly expressed in AML cells. Further research uncovered that low expression of <i>HOPX</i> can repress the proliferation activity, anti-apoptotic ability, and differentiation blockage of AML cells. Moreover, mechanistically, <i>HOPX</i> induced AML differentiation blockage and malignant progression through interaction with HDAC. <i>HOPX</i> can serve as a prognostic marker for AML and can interact with <i>HDAC2</i> to induce AML differentiation blockage and malignant progression.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined targeting of Hedgehog/GLI1 and Wnt/β-catenin pathways in mantle cell lymphoma","authors":"Yan Han,&nbsp;Chuntuan Li,&nbsp;Shengquan Liu,&nbsp;Jingjing Gao,&nbsp;Yanjun He,&nbsp;Huifang Xiao,&nbsp;Qi Chen,&nbsp;Yan Zheng,&nbsp;Hongyuan Chen,&nbsp;Xiongpeng Zhu","doi":"10.1002/hon.3305","DOIUrl":"https://doi.org/10.1002/hon.3305","url":null,"abstract":"<p>Mantle cell lymphoma (MCL) is a rare and aggressive form of non-Hodgkin lymphoma. Challenges in its treatment include relapse, drug resistance, and a short survival period. The Hedgehog/GLI1 (Hh/GLI1) and Wnt/β-catenin pathways are crucial in cancer cell proliferation, survival, and drug resistance, making them significant targets for anticancer research. This study aimed to assess the effectiveness of combining inhibitors for both pathways against MCL and investigate the underlying molecular mechanisms. The co-expression of key proteins from the Hh/GLI1 and Wnt/β-catenin pathways was observed in MCL. Targeting the Hh/GLI1 pathway with the GLI1 inhibitor GANT61 and the Wnt/β-catenin pathway with the CBP/β-catenin transcription inhibitor ICG-001, dual-target therapy was demonstrated to synergistically suppressed the activity of MCL cells. This approach promoted MCL cell apoptosis, induced G0/G1 phase blockade, decreased the percentage of S-phase cells, and enhanced the sensitivity of MCL cells to the drugs adriamycin and ibrutinib. Both GANT61 and ICG-001 downregulated GLI1 and β-catenin while upregulating GSK-3β expression. The interaction between Hh/GLI1 and Wnt/β-catenin pathways was mediated by GANT61-dependent Hh/GLI1 inhibition. Moreover, GLI1 knockdown combined with ICG-001 synergistically induced apoptosis and increased drug sensitivity of MCL cells to doxorubicin and ibrutinib. GANT61 attenuated the overexpression of β-catenin and decreased the inhibition of GSK-3β in MCL cells. Overall, the combined targeting of both the Hh/GLI1 and Wnt/β-catenin pathways was more effective in suppressing proliferation, inducing G0/G1 cycle retardation, promoting apoptosis, and increasing drug sensitivity of MCL cells than mono treatments. These findings emphasize the potential of combinatorial therapy for treating MCL patients.</p>","PeriodicalId":12882,"journal":{"name":"Hematological Oncology","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/hon.3305","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}