Lymphoma is a cancer affecting the lymphatic system that fights infections and diseases. In addition to surgery, radiotherapy, and chemotherapy, novel approaches have recently been investigated, such as phytostilbenes in treating lymphoma. Phytostilbenes are natural compounds present in various plants and have been shown to have different therapeutic effects, including anticancer properties. Resveratrol is a main phytostilbene with various derivates followed by pterostilbene and piceatannol. Studies have revealed that phytostilbenes can suppress the growth and proliferation of lymphoma cells by inducing apoptosis and inhibiting specific enzyme activity in cancer cell survival. The compounds also have antiinflammatory effects contributing to reducing lymphoma-associated inflammation. Additionally, phytostilbenes have been shown to increase the immune system's ability to fight cancer cells by activating immune cells (T-cells and natural killer cells). This review investigates the potential therapeutic effects of phytostilbenes, including resveratrol, pterostilbene, piceatannol, and pinosylvin, against lymphoma.
{"title":"Phytostilbenes in lymphoma: Focuses on the mechanistic and clinical prospects of resveratrol, pterostilbene, piceatannol, and pinosylvin","authors":"Pouya Goleij , Pantea Majma Sanaye , Mehregan Babamohamadi , Mohammad Amin Khazeei Tabari , Roshanak Amirian , Aryan Rezaee , Hamed Mirzaei , Alan Prem Kumar , Gautam Sethi , Sarvin Sadreddini , Philippe Jeandet , Haroon Khan","doi":"10.1016/j.leukres.2024.107464","DOIUrl":"10.1016/j.leukres.2024.107464","url":null,"abstract":"<div><p>Lymphoma is a cancer affecting the lymphatic system that fights infections and diseases. In addition to surgery, radiotherapy, and chemotherapy, novel approaches have recently been investigated, such as phytostilbenes in treating lymphoma. Phytostilbenes are natural compounds present in various plants and have been shown to have different therapeutic effects, including anticancer properties. Resveratrol is a main phytostilbene with various derivates followed by pterostilbene and piceatannol. Studies have revealed that phytostilbenes can suppress the growth and proliferation of lymphoma cells by inducing apoptosis and inhibiting specific enzyme activity in cancer cell survival. The compounds also have antiinflammatory effects contributing to reducing lymphoma-associated inflammation. Additionally, phytostilbenes have been shown to increase the immune system's ability to fight cancer cells by activating immune cells (T-cells and natural killer cells). This review investigates the potential therapeutic effects of phytostilbenes, including resveratrol, pterostilbene, piceatannol, and pinosylvin, against lymphoma.</p></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"138 ","pages":"Article 107464"},"PeriodicalIF":2.7,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139977342","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}
In a meta-analysis of 5 trials, the addition of gemtuzumab ozogamicin (GO) to intensive induction chemotherapy led to a survival benefit in patients with core-binding factor (CBF) acute myeloid leukemia (AML). Given the heterogeneous incorporation of GO in clinical trials, the ideal dose and schedule remains unclear. We conducted a single-center retrospective analysis to compare outcomes of patients with CBF-AML treated with intensive induction chemotherapy, with or without a single dose of GO 3 mg/m2, during induction only. We included 87 patients (GO=32, control=55). The composite complete remission (cCR) rate was higher in the control group (93%) compared to the GO group (82%) (p<0.001). The rate of measurable residual disease (MRD) negative cCR, by flow cytometry, was similar between both groups. There were no significant differences between the two groups in terms of toxicity. The 3-year relapse-free survival (RFS) for both groups was similar (71% vs 68%, p=0.5). The 3-year overall survival (OS) for the GO group was 68%, compared to 66% for the control group (p=0.9).In multivariable analysis, age and MRD positive status were risk factors for inferior outcomes. We find that survival of patients with CBF-AML is favorable in the real-world setting. The addition of single-dose GO, during induction, did not lead to a higher remission rate or survival benefit, when compared to intensive chemotherapy without GO. Further investigation into the incorporation of GO in the treatment algorithm for CBF-AML is needed.
一项对5项试验进行的荟萃分析显示,在强化诱导化疗的基础上加用吉妥珠单抗-奥佐米星(GO)可使核心结合因子(CBF)急性髓性白血病(AML)患者的生存获益。鉴于GO在临床试验中的应用不尽相同,理想的剂量和疗程仍不明确。我们进行了一项单中心回顾性分析,比较了仅在诱导期间接受强化诱导化疗的 CBF-AML 患者的疗效,以及是否单剂量使用 3mg/m GO。我们纳入了 87 例患者(GO=32 例,对照组=55 例)。对照组的综合完全缓解(cCR)率(93%)高于 GO 组(82%)(P<0.001)。通过流式细胞术检测,两组的可测量残留疾病(MRD)阴性 cCR 率相似。两组在毒性方面无明显差异。两组的3年无复发生存率(RFS)相似(71% vs 68%,P=0.5)。GO组的3年总生存率(OS)为68%,而对照组为66%(P=0.9)。我们发现,在现实世界中,CBF-AML 患者的生存率较高。与不使用GO的强化化疗相比,在诱导期间加用单剂量GO并不能提高缓解率或生存率。需要进一步研究将 GO 纳入 CBF-AML 治疗方案的可能性。
{"title":"Addition of single dose gemtuzumab ozogamicin to intensive induction chemotherapy in core-binding factor acute myeloid leukemia","authors":"Garrett Bourne , Kendall Diebold , Manuel Espinoza-Gutarra , Zaid Al-Kadhimi , Kimo Bachiashvili , Sravanti Rangaraju , Pankit Vachhani , Ravi Bhatia , Omer Jamy","doi":"10.1016/j.leukres.2024.107467","DOIUrl":"10.1016/j.leukres.2024.107467","url":null,"abstract":"<div><p>In a meta-analysis of 5 trials, the addition of gemtuzumab ozogamicin (GO) to intensive induction chemotherapy led to a survival benefit in patients with core-binding factor (CBF) acute myeloid leukemia (AML). Given the heterogeneous incorporation of GO in clinical trials, the ideal dose and schedule remains unclear. We conducted a single-center retrospective analysis to compare outcomes of patients with CBF-AML treated with intensive induction chemotherapy, with or without a single dose of GO 3 mg/m<sup>2</sup>, during induction only. We included 87 patients (GO=32, control=55). The composite complete remission (cCR) rate was higher in the control group (93%) compared to the GO group (82%) (p<0.001). The rate of measurable residual disease (MRD) negative cCR, by flow cytometry, was similar between both groups. There were no significant differences between the two groups in terms of toxicity. The 3-year relapse-free survival (RFS) for both groups was similar (71% vs 68%, p=0.5). The 3-year overall survival (OS) for the GO group was 68%, compared to 66% for the control group (p=0.9).In multivariable analysis, age and MRD positive status were risk factors for inferior outcomes. We find that survival of patients with CBF-AML is favorable in the real-world setting. The addition of single-dose GO, during induction, did not lead to a higher remission rate or survival benefit, when compared to intensive chemotherapy without GO. Further investigation into the incorporation of GO in the treatment algorithm for CBF-AML is needed.</p></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"139 ","pages":"Article 107467"},"PeriodicalIF":2.7,"publicationDate":"2024-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140033095","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}
Pub Date : 2024-02-27DOI: 10.1016/j.leukres.2024.107468
Sharon Zhong , Heena Kurish , Robert Walchack , Hong Li , Jessi Edwards , Abhay Singh , Anjali Advani
Background/rationale
Most patients with acute myeloid leukemia (AML) develop relapsed or refractory (R/R) disease after receiving initial induction chemotherapy. Salvage chemotherapy followed by allogeneic hematopoietic stem cell transplantation (alloHSCT) is the only curative therapy for R/R AML. Mitoxantrone, etoposide, and cytarabine (MEC) is the current standard of care salvage regimen for R/R AML at Cleveland Clinic. The primary objective was to determine the overall remission rate (ORR: defined as patients achieving complete remission (CR) or complete remission with incomplete hematologic recovery (CRi)) in R/R AML patients who received MEC.
Methods
Adult patients with R/R AML treated with MEC between July 1, 2014 and September 30, 2022 were included. ORR and its association with baseline characteristics were determined. Secondary outcomes included overall survival (OS), event-free survival (EFS), relapse-free survival (RFS), and safety.
Results
Sixty patients were evaluated. The ORR was 51.7% (33.3% CR and 18.3% CRi). The median time from receipt of MEC to CR/CRi was 7.7 weeks. Patients with bone marrow blasts ≤20% and peripheral blood blasts ≤30% at MEC initiation were more than twice as likely to achieve CR/CRi compared to those with a higher blast burden. The median OS was 6.3 months. Twenty-four (40.0%) patients proceeded to alloHSCT. Twenty-one (35.0%) patients were transferred to the intensive care unit (ICU) during their admission.
Conclusions
MEC is an effective salvage regimen for patients with R/R AML, especially among those with low disease burden at initiation. Febrile neutropenia, infections, and severe oral mucositis were common with MEC administration.
{"title":"Efficacy and safety of mitoxantrone, etoposide, and cytarabine for treatment of relapsed or refractory acute myeloid leukemia","authors":"Sharon Zhong , Heena Kurish , Robert Walchack , Hong Li , Jessi Edwards , Abhay Singh , Anjali Advani","doi":"10.1016/j.leukres.2024.107468","DOIUrl":"10.1016/j.leukres.2024.107468","url":null,"abstract":"<div><h3>Background/rationale</h3><p>Most patients with acute myeloid leukemia (AML) develop relapsed or refractory (R/R) disease after receiving initial induction chemotherapy. Salvage chemotherapy followed by allogeneic hematopoietic stem cell transplantation (alloHSCT) is the only curative therapy for R/R AML. Mitoxantrone, etoposide, and cytarabine (MEC) is the current standard of care salvage regimen for R/R AML at Cleveland Clinic. The primary objective was to determine the overall remission rate (ORR: defined as patients achieving complete remission (CR) or complete remission with incomplete hematologic recovery (CRi)) in R/R AML patients who received MEC.</p></div><div><h3>Methods</h3><p>Adult patients with R/R AML treated with MEC between July 1, 2014 and September 30, 2022 were included. ORR and its association with baseline characteristics were determined. Secondary outcomes included overall survival (OS), event-free survival (EFS), relapse-free survival (RFS), and safety.</p></div><div><h3>Results</h3><p>Sixty patients were evaluated. The ORR was 51.7% (33.3% CR and 18.3% CRi). The median time from receipt of MEC to CR/CRi was 7.7 weeks. Patients with bone marrow blasts ≤20% and peripheral blood blasts ≤30% at MEC initiation were more than twice as likely to achieve CR/CRi compared to those with a higher blast burden. The median OS was 6.3 months. Twenty-four (40.0%) patients proceeded to alloHSCT. Twenty-one (35.0%) patients were transferred to the intensive care unit (ICU) during their admission.</p></div><div><h3>Conclusions</h3><p>MEC is an effective salvage regimen for patients with R/R AML, especially among those with low disease burden at initiation. Febrile neutropenia, infections, and severe oral mucositis were common with MEC administration.</p></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"139 ","pages":"Article 107468"},"PeriodicalIF":2.7,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140032951","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}
This study evaluated the impact of adipose tissue indices on prognosis of HL.
Methods
Fifty-five patients with newly diagnosed Hodgkin Lymphoma were evaluated retrospectively for association with adipose tissue indices (total abdominal tissue volume, radiodensity, subcutaneous and visceral adipose tissue SUVmax value and prognostic factors for Hodgkin Lymphoma such as IPS-3, IPS-7, stage, sedimentation, progression free and overall survival.
Results
For IPS-3, SAT SUVmax and TAAT radiodensity were significantly increased in high-risk patients (2and 3) compared to group 0 and 1. For IPS-7, total abdominal adipose volume was significantly decreased in high-risk patients, SAT SUVmax significantly increased in high-risk patients and decreased in low-risk patients. In addition, SAT SUVmax was significantly increased in patients with high sedimentation rate, with B symptoms and who passed away during follow-up. SAT SUVmax showed moderate positive correlation with sedimentation, IPS-3, IPS-7, and stage. In addition, it was observed that TAAT radiodensity and SAT SUVmax were significantly better for determining prognosis than other adipose tissue indices. Roc analysis showed that the diagnostic value of all adipose tissue indices in predicting IPS-3 and IPS-7 prognoses were statistically significant.
Conclusion
SAT SUVmax and TAAT radiodensity were two new and independent markers with diagnostic value in predicting prognosis.
方法回顾性评估55例新诊断的霍奇金淋巴瘤患者的脂肪组织指数(腹部组织总体积、放射性密度、皮下和内脏脂肪组织SUVmax值)与霍奇金淋巴瘤预后因素(如IPS-3、IPS-7、分期、血沉、无进展生存期和总生存期)的相关性。结果 在IPS-3中,与0组和1组相比,高危患者(2组和3组)的SAT SUVmax和TAAT放射密度明显增加。 在IPS-7中,高危患者的腹部脂肪总量明显减少,SAT SUVmax在高危患者中明显增加,在低危患者中减少。此外,血沉高、有 B 型症状和在随访期间去世的患者的 SAT SUVmax 明显增高。SAT SUVmax 与血沉、IPS-3、IPS-7 和分期呈中度正相关。此外,还观察到 TAAT 放射性密度和 SAT SUVmax 在判断预后方面明显优于其他脂肪组织指数。Roc分析表明,所有脂肪组织指数在预测IPS-3和IPS-7预后方面的诊断价值均具有统计学意义。
{"title":"Adipose tissue indices predict prognosis in hodgkin lymphoma","authors":"Demircan Özbalcı , Mehmet Erdoğan , Emine Güçhan Alanoğlu , Sevim Süreyya Şengül , Kamuran Yüceer , Hande Nur Eroğlu , Samet Yağcı","doi":"10.1016/j.leukres.2024.107457","DOIUrl":"10.1016/j.leukres.2024.107457","url":null,"abstract":"<div><h3>Introduction background</h3><p>This study evaluated the impact of adipose tissue indices on prognosis of HL.</p></div><div><h3>Methods</h3><p>Fifty-five patients with newly diagnosed Hodgkin Lymphoma were evaluated retrospectively for association with adipose tissue indices (total abdominal tissue volume, radiodensity, subcutaneous and visceral adipose tissue SUVmax value and prognostic factors for Hodgkin Lymphoma such as IPS-3, IPS-7, stage, sedimentation, progression free and overall survival.</p></div><div><h3>Results</h3><p>For IPS-3, SAT SUVmax and TAAT radiodensity were significantly increased in high-risk patients (2and 3) compared to group 0 and 1. For IPS-7, total abdominal adipose volume was significantly decreased in high-risk patients, SAT SUVmax significantly increased in high-risk patients and decreased in low-risk patients. In addition, SAT SUVmax was significantly increased in patients with high sedimentation rate, with B symptoms and who passed away during follow-up. SAT SUVmax showed moderate positive correlation with sedimentation, IPS-3, IPS-7, and stage. In addition, it was observed that TAAT radiodensity and SAT SUVmax were significantly better for determining prognosis than other adipose tissue indices. Roc analysis showed that the diagnostic value of all adipose tissue indices in predicting IPS-3 and IPS-7 prognoses were statistically significant.</p></div><div><h3>Conclusion</h3><p>SAT SUVmax and TAAT radiodensity were two new and independent markers with diagnostic value in predicting prognosis.</p></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"138 ","pages":"Article 107457"},"PeriodicalIF":2.7,"publicationDate":"2024-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139889352","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}
Pub Date : 2024-02-12DOI: 10.1016/j.leukres.2024.107455
Rongjuan Zhang , Xinhong Yang , Xiaomin Shi , Enhong Xing , Lihong Wang , Changlai Hao , Zhihua Zhang
Objective
To explore the involvement of TFEB-mediated autophagy-lysosomal mechanisms in multiple myeloma (MM) during bortezomib treatment.
Methods
MM cells were exposed to bortezomib or subjected to TFEB knockdown. CCK assay was used to assess the cell proliferation. Western blotting and fluorescent staining were conducted to examine autophagy and lysosomes. The TFEB expression pattern was analyzed, and whole transcriptome sequencing was carried out. Additionally, TFEB target genes were predicted using the GTRD(http://gtrd.biouml.org/) website, and pathway analysis was performed.
Results
Bortezomib demonstrated a dose-dependent and time dependent inhibition of cell proliferation. In MM cells treated with bortezomib, LC3B, Beclin-1, TFEB, and Lamp1 exhibited upregulation in a time- and concentration-dependent manner. LysoTracker dye labeling showed an increase in lysosomes in the bortezomib-treated group. Moreover, bortezomib elevated the expression of lysosome-associated factor Lamp1. Bortezomib promoted the nuclear translocation of TFEB, leading to decreased cytoplasmic TFEB and increased nuclear TFEB. TFEB gene silencing reversed bortezomib's inhibitory effect on MM cell lines, significantly reducing autophagosome expression and lysosome numbers. Furthermore, bioinformatic analysis identified the MAPK pathway as a potential downstream target of TFEB.
Conclusion
Bortezomib effectively inhibits MM cell proliferation and induces autophagy, partly through TFEB-mediated mechanisms, with potential involvement of the MAPK pathway.
方法 将多发性骨髓瘤(MM)细胞暴露于硼替佐米或敲除 TFEB。采用 CCK 检测法评估细胞增殖情况。用 Western 印迹法和荧光染色法检测自噬和溶酶体。分析了 TFEB 的表达模式,并进行了全转录组测序。此外,还利用 GTRD(http://gtrd.biouml.org/) 网站预测了 TFEB 的靶基因,并进行了通路分析。结果硼替佐米对细胞增殖的抑制具有剂量依赖性和时间依赖性。在用硼替佐米处理的 MM 细胞中,LC3B、Beclin-1、TFEB 和 Lamp1 呈时间和浓度依赖性上调。溶酶体追踪染料标记显示,硼替佐米处理组的溶酶体有所增加。此外,硼替佐米还能提高溶酶体相关因子Lamp1的表达。硼替佐米促进了TFEB的核转位,导致细胞质中的TFEB减少,而细胞核中的TFEB增加。TFEB基因沉默可逆转硼替佐米对MM细胞株的抑制作用,显著减少自噬体的表达和溶酶体的数量。结论硼替佐米能有效抑制 MM 细胞增殖并诱导自噬,部分是通过 TFEB 介导的机制,MAPK 途径也可能参与其中。
{"title":"Bortezomib modulated the autophagy-lysosomal pathway in a TFEB-dependent manner in multiple myeloma","authors":"Rongjuan Zhang , Xinhong Yang , Xiaomin Shi , Enhong Xing , Lihong Wang , Changlai Hao , Zhihua Zhang","doi":"10.1016/j.leukres.2024.107455","DOIUrl":"10.1016/j.leukres.2024.107455","url":null,"abstract":"<div><h3>Objective</h3><p>To explore the involvement of TFEB-mediated autophagy-lysosomal mechanisms in multiple myeloma (MM) during bortezomib treatment.</p></div><div><h3>Methods</h3><p>MM cells were exposed to bortezomib or subjected to TFEB knockdown. CCK assay was used to assess the cell proliferation. Western blotting and fluorescent staining were conducted to examine autophagy and lysosomes. The TFEB expression pattern was analyzed, and whole transcriptome sequencing was carried out. Additionally, TFEB target genes were predicted using the GTRD(http://gtrd.biouml.org/) website, and pathway analysis was performed.</p></div><div><h3>Results</h3><p>Bortezomib demonstrated a dose-dependent and time dependent inhibition of cell proliferation. In MM cells treated with bortezomib, LC3B, Beclin-1, TFEB, and Lamp1 exhibited upregulation in a time- and concentration-dependent manner. LysoTracker dye labeling showed an increase in lysosomes in the bortezomib-treated group. Moreover, bortezomib elevated the expression of lysosome-associated factor Lamp1. Bortezomib promoted the nuclear translocation of TFEB, leading to decreased cytoplasmic TFEB and increased nuclear TFEB. TFEB gene silencing reversed bortezomib's inhibitory effect on MM cell lines, significantly reducing autophagosome expression and lysosome numbers. Furthermore, bioinformatic analysis identified the MAPK pathway as a potential downstream target of TFEB.</p></div><div><h3>Conclusion</h3><p>Bortezomib effectively inhibits MM cell proliferation and induces autophagy, partly through TFEB-mediated mechanisms, with potential involvement of the MAPK pathway.</p></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"138 ","pages":"Article 107455"},"PeriodicalIF":2.7,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139829517","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}
Pub Date : 2024-02-01DOI: 10.1016/j.leukres.2024.107441
M. Tarek Elghetany , Mrinal M. Patnaik , Joseph D. Khoury
Inherited bone marrow failure syndromes and germline predisposition syndromes (IBMFS/GPS) are associated with increased risk for hematologic malignancies, particularly myeloid neoplasms, such as myelodysplastic neoplasms (MDS) and acute myeloid leukemia (AML). The diagnosis of MDS in these syndromes poses difficulty due to frequent bone marrow hypocellularity and the presence of some degree of dysplastic features related to the underlying germline defect causing abnormal maturation of one or more cell lines. Yet, the diagnosis of MDS is usually associated with a worse outcome in several IBMFS/GPS. Criteria for the diagnosis of MDS in IBMFS/GPS have not been standardized with some authors suggesting a mixture of morphologic, cytogenetic, and genetic criteria. This review highlights these challenges and suggests a more standardized approach to nomenclature and diagnostic criteria.
{"title":"Myelodysplastic neoplasms evolving from inherited bone marrow failure syndromes / germline predisposition syndromes: Back under the microscope","authors":"M. Tarek Elghetany , Mrinal M. Patnaik , Joseph D. Khoury","doi":"10.1016/j.leukres.2024.107441","DOIUrl":"10.1016/j.leukres.2024.107441","url":null,"abstract":"<div><p><span><span><span>Inherited bone marrow failure syndromes and </span>germline predisposition syndromes (IBMFS/GPS) are associated with increased risk for </span>hematologic malignancies, particularly myeloid neoplasms, such as myelodysplastic neoplasms (MDS) and </span>acute myeloid leukemia<span> (AML). The diagnosis of MDS in these syndromes poses difficulty due to frequent bone marrow hypocellularity and the presence of some degree of dysplastic features related to the underlying germline defect causing abnormal maturation of one or more cell lines. Yet, the diagnosis of MDS is usually associated with a worse outcome in several IBMFS/GPS. Criteria for the diagnosis of MDS in IBMFS/GPS have not been standardized with some authors suggesting a mixture of morphologic, cytogenetic, and genetic criteria. This review highlights these challenges and suggests a more standardized approach to nomenclature and diagnostic criteria.</span></p></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"137 ","pages":"Article 107441"},"PeriodicalIF":2.7,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139554438","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}
Pub Date : 2024-02-01DOI: 10.1016/j.leukres.2024.107452
Hannah Goulart , Dahniel Sastow , Erin Moshier , Lily Martin , John Mascarenhas , Douglas Tremblay
Patients with acute myeloid leukemia (AML) may experience extramedullary involvement when disease is present outside of the blood and bone marrow. In particular, the presence of central nervous system (CNS) involvement has traditionally been thought of as a poor prognostic factor. In the presently available literature, there is a paucity of conclusive data surrounding CNS AML given its rarity and lack of unified screening practices. Thus, we performed a systematic review and meta-analysis in order to more definitively characterize survival outcomes in this patient population. In this meta-analysis, we evaluated survival outcomes and response rates from clinical studies on patients with AML stratified by the presence of CNS involvement. Twelve studies were included in the meta-analysis with a resulting hazard ratio (HR) for overall survival (OS) of 1.34 with a 95 % CI of 1.14 to 1.58. These findings suggest that CNS involvement in adult patients with AML is associated with an increased hazard of mortality compared to those patients without CNS involvement. As such, CNS involvement should be viewed as negative prognostic marker, and attention should be made to ensure prompt identification and treatment of patients who experience this complication.
{"title":"Systematic review and meta-analysis evaluating clinical outcomes in adult acute myeloid leukemia patients with central nervous system involvement","authors":"Hannah Goulart , Dahniel Sastow , Erin Moshier , Lily Martin , John Mascarenhas , Douglas Tremblay","doi":"10.1016/j.leukres.2024.107452","DOIUrl":"https://doi.org/10.1016/j.leukres.2024.107452","url":null,"abstract":"<div><p>Patients with acute myeloid leukemia (AML) may experience extramedullary involvement when disease is present outside of the blood and bone marrow. In particular, the presence of central nervous system (CNS) involvement has traditionally been thought of as a poor prognostic factor. In the presently available literature, there is a paucity of conclusive data surrounding CNS AML given its rarity and lack of unified screening practices. Thus, we performed a systematic review and meta-analysis in order to more definitively characterize survival outcomes in this patient population. In this meta-analysis, we evaluated survival outcomes and response rates from clinical studies on patients with AML stratified by the presence of CNS involvement. Twelve studies were included in the meta-analysis with a resulting hazard ratio (HR) for overall survival (OS) of 1.34 with a 95 % CI of 1.14 to 1.58. These findings suggest that CNS involvement in adult patients with AML is associated with an increased hazard of mortality compared to those patients without CNS involvement. As such, CNS involvement should be viewed as negative prognostic marker, and attention should be made to ensure prompt identification and treatment of patients who experience this complication.</p></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"137 ","pages":"Article 107452"},"PeriodicalIF":2.7,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139709733","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}
Pub Date : 2024-02-01DOI: 10.1016/j.leukres.2024.107451
Kai Zhu , Fengquan Gou , Ziwen Zhao , Ke Xu , Jian Song , Hongyi Jiang , Feng Zhang , Yanli Yang , Jiajia Li
Background
Circular RNAs (circRNAs) are associated with development and progression of multiple myeloma (MM). However, the role and mechanism of circ_0005615 in MM have not been elucidated.
Methods
Circ_0005615 was determined by GEO database. quantitative RT-PCR was performed to confirm the expression of circ_0005615 in peripheral blood of MM patients and MM cells. The roles of circ_0005615 in MM were analyzed using CCK8, transwell invasion, cell apoptosis and tumor xenograft experiments. Bioinformatics tools, RIP and RNA pull down assays were conducted to explore the downstream of circ_0005615. Furthermore, the mechanism was investigated by quantitative RT-PCR, western blot, dot blot and meRIP-PCR assays.
Results
Circ_0005615 was upregulated in MM. Overexpression of circ_0005615 promoted cell viability and invasion, and suppressed apoptosis in vitro, which were opposite when circ_0005615 was knockdowned. Mechanistically, EIF4A3, a RNA-binding protein (RBP), could directly bind to circ_0005615 and ALKBH5, where ALKBH5 could directly combine with MAP3K4, forming a circ_0005615- EIF4A3-ALKBH5-MAP3K4 module. Furthermore, circ_0005615 overexpression increased m6A methylation of MAP3K4 by inhibiting ALKBH5, leading to decreased MAP3K4. Further functional experiments indicated that ALKBH5 overexpression weakened the promoting roles of circ_0005615 overexpression in MAP3K4 m6A methylation and tumor progression in MM. The above functions and mechanism were also verified in vivo.
Conclusions
Elevated circ_0005615 decreased MAP3K4 mediated by ALKBH5 through interacting with EIF4A3, thereby accelerating MM progression. Circ_0005615 might be a promising biomarker and target of MM.
{"title":"Circ_0005615 enhances multiple myeloma progression through interaction with EIF4A3 to regulate MAP3K4 m6A modification mediated by ALKBH5","authors":"Kai Zhu , Fengquan Gou , Ziwen Zhao , Ke Xu , Jian Song , Hongyi Jiang , Feng Zhang , Yanli Yang , Jiajia Li","doi":"10.1016/j.leukres.2024.107451","DOIUrl":"10.1016/j.leukres.2024.107451","url":null,"abstract":"<div><h3>Background</h3><p>Circular RNAs (circRNAs) are associated with development and progression of multiple myeloma (MM). However, the role and mechanism of circ_0005615 in MM have not been elucidated.</p></div><div><h3>Methods</h3><p>Circ_0005615 was determined by GEO database. quantitative RT-PCR was performed to confirm the expression of circ_0005615 in peripheral blood of MM patients and MM cells. The roles of circ_0005615 in MM were analyzed using CCK8, transwell invasion, cell apoptosis and tumor xenograft experiments. Bioinformatics tools, RIP and RNA pull down assays were conducted to explore the downstream of circ_0005615. Furthermore, the mechanism was investigated by quantitative RT-PCR, western blot, dot blot and meRIP-PCR assays.</p></div><div><h3>Results</h3><p>Circ_0005615 was upregulated in MM. Overexpression of circ_0005615 promoted cell viability and invasion, and suppressed apoptosis <em>in vitro</em>, which were opposite when circ_0005615 was knockdowned. Mechanistically, EIF4A3, a RNA-binding protein (RBP), could directly bind to circ_0005615 and ALKBH5, where ALKBH5 could directly combine with MAP3K4, forming a circ_0005615- EIF4A3-ALKBH5-MAP3K4 module. Furthermore, circ_0005615 overexpression increased m6A methylation of MAP3K4 by inhibiting ALKBH5, leading to decreased MAP3K4. Further functional experiments indicated that ALKBH5 overexpression weakened the promoting roles of circ_0005615 overexpression in MAP3K4 m6A methylation and tumor progression in MM. The above functions and mechanism were also verified <em>in vivo</em>.</p></div><div><h3>Conclusions</h3><p>Elevated circ_0005615 decreased MAP3K4 mediated by ALKBH5 through interacting with EIF4A3, thereby accelerating MM progression. Circ_0005615 might be a promising biomarker and target of MM.</p></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"141 ","pages":"Article 107451"},"PeriodicalIF":2.7,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139663308","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}