Leukemia research最新文献

英文中文

Clinical applicability of the ELN2020 criteria for tyrosine kinase inhibitor discontinuation in chronic myeloid leukemia: insights from a multicenter retrospective study in real-world practice

IF 2.1 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2025-04-04 DOI: 10.1016/j.leukres.2025.107689

Yuto Hibino , Shin Fujisawa , Katsumichi Fujimaki , Maki Hagihara , Hiroyuki Fujita , Masatsugu Tanaka , Kosuke Takayama , Takaaki Takeda , Ayako Matsumura , Taisei Suzuki , Yoshimi Ishii , Yuki Nakajima , Takuya Miyazaki , Hideaki Nakajima

The prognosis of chronic myeloid leukemia has significantly improved with the introduction of tyrosine kinase inhibitors (TKIs). However, indefinite TKI treatment can lead to adverse effects and high costs. Recent studies have suggested that treatment-free remission (TFR) is achievable in patients with a deep molecular response (DMR). The present multicenter, retrospective observational study conducted in Japan evaluated the applicability of the European LeukemiaNet (ELN) 2020 TKI discontinuation criteria, which recommend TKI therapy of ≥ 5 years with sustained MR⁴ for ≥ 3 years or MR^4.5 for ≥ 2 years. A total of 100 patients who discontinued TKI therapy were analyzed, with 70 meeting the ELN2020 criteria. The overall 12-month TFR rate was 71.9 %. Univariate analysis showed that both the duration of DMR and TKI therapy were significantly associated with TFR, with hazard ratios (HR) of 0.305 and 0.450, respectively. Only DMR duration remained significant (HR 0.362) in multivariate analysis. Patients who lost MMR after TKI discontinuation rapidly re-achieved molecular response upon TKI resumption. The most common reason for TKI discontinuation was elective cessation, followed by adverse events, among which pleural effusion due to dasatinib was the most frequent. The results of this study, the first to assess the ELN2020 criteria in a Japanese cohort, suggest that the criteria are applicable in real-world clinical practice.

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引用次数: 0

Safety, tolerability, and pharmacokinetics of ASP1235 in relapsed or refractory acute myeloid leukemia: A phase 1 study

IF 2.1 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2025-04-02 DOI: 10.1016/j.leukres.2025.107690

Monzr M. Al Malki , Mark D. Minden , Elizabeth Shima Rich , Jason E. Hill , Stanley C. Gill , Alan Fan , Christine E. Fredericks , Amir T. Fathi , Maher Abdul-Hay

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy. Although new agents including targeted therapies for relapsed or refractory (R/R) AML have been introduced, poor outcomes remain, requiring the need for novel approaches. One novel approach is the use of antibody-drug conjugates (ADCs). We conducted an early phase clinical trial with ASP1235, an ADC targeting FMS-like tyrosine kinase 3. In total, 43 patients with R/R AML were treated with ASP1235. The most common adverse events (AEs) included elevated liver transaminase levels, ocular toxicity, and muscular weakness. Ocular treatment-emergent AEs (TEAEs) were observed in 53 % of patients; most were mild or moderate in severity. The most common ocular TEAEs were blurred vision, dry eye, keratitis, photophobia, and reduced visual acuity. Serious (grade ≥3) ocular TEAEs occurred in 16.3 % of patients, with only 1 patient experiencing grade 4 keratitis. Six patients achieved composite complete remission (complete remission [CR] + CR with incomplete hematologic recovery + CR with incomplete platelet recovery), 2 of whom proceeded to hematopoietic cell transplantation with long-term leukemia-free survival. This trial was registered at www.clinicaltrials.gov as #NCT02864290.

{"title":"Safety, tolerability, and pharmacokinetics of ASP1235 in relapsed or refractory acute myeloid leukemia: A phase 1 study","authors":"Monzr M. Al Malki , Mark D. Minden , Elizabeth Shima Rich , Jason E. Hill , Stanley C. Gill , Alan Fan , Christine E. Fredericks , Amir T. Fathi , Maher Abdul-Hay","doi":"10.1016/j.leukres.2025.107690","DOIUrl":"10.1016/j.leukres.2025.107690","url":null,"abstract":"<div><div>Acute myeloid leukemia (AML) is an aggressive hematologic malignancy. Although new agents including targeted therapies for relapsed or refractory (R/R) AML have been introduced, poor outcomes remain, requiring the need for novel approaches. One novel approach is the use of antibody-drug conjugates (ADCs). We conducted an early phase clinical trial with ASP1235, an ADC targeting FMS-like tyrosine kinase 3. In total, 43 patients with R/R AML were treated with ASP1235. The most common adverse events (AEs) included elevated liver transaminase levels, ocular toxicity, and muscular weakness. Ocular treatment-emergent AEs (TEAEs) were observed in 53 % of patients; most were mild or moderate in severity. The most common ocular TEAEs were blurred vision, dry eye, keratitis, photophobia, and reduced visual acuity. Serious (grade ≥3) ocular TEAEs occurred in 16.3 % of patients, with only 1 patient experiencing grade 4 keratitis. Six patients achieved composite complete remission (complete remission [CR] + CR with incomplete hematologic recovery + CR with incomplete platelet recovery), 2 of whom proceeded to hematopoietic cell transplantation with long-term leukemia-free survival. This trial was registered at <span><span>www.clinicaltrials.gov</span><svg><path></path></svg></span> as #NCT02864290.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"152 ","pages":"Article 107690"},"PeriodicalIF":2.1,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143799876","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}

引用次数: 0

Response to venetoclax in patients with blastic plasmacytoid dendritic cell neoplasm

IF 2.1 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2025-03-22 DOI: 10.1016/j.leukres.2025.107678

Kirsty M Sharplin, Catherine Vassiliou, James Nguyen, Bryone J. Kuss, Stephen B Ting, Hilda Mangos, Hamish Scott, Anna Brown, Piers Blombery, Andrew Wei, David M. Ross

引用次数: 0

Comprehensive analysis of tyrosine kinase domain mutations and imatinib resistance in chronic myeloid leukemia patients 慢性髓性白血病患者酪氨酸激酶域突变与伊马替尼耐药性的综合分析。

IF 2.1 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2025-03-17 DOI: 10.1016/j.leukres.2025.107679

Somprakash Dhangar , Chandrakala Shanmukhaiah , Jagdeeshwar Ghatanatti , Leena Sawant , Nehakumari Maurya , Babu Rao Vundinti

Tyrosine kinase domain mutations (TKDMs) plays an important role in prognosis of chronic myeloid leukemia (CML). The aim of the present study was to identify the TKDMs associated with imatinib mesylate (IM) drug resistant in CML, following European leukemia Net (ELN) guidelines. Direct sequencing analysis revealed point mutations in 69.44 % (50/72), compound/ polyclonal mutations in 11.11 % (8/72) and large deletions in 4.16 % (3/72) of IM non-responder CML patients. Additionally, we have identified low level mutations in 30.55 % of warning group patients through NGS analysis, that include singly occurring point mutations (5) and polyclonal (6) mutations with mutant allele frequency ranging from 1.1 % to 14.70 %. The low-level mutations detected through NGS in warning group patients; may be responsible for suboptimal response in our study. However, follow-up studies are important to understand the mechanism of clonal evolution. We also identified 5 novel mutations that had not been reported in public databases which expands the spectrum of known mutations in BCR::ABL1 fusion gene. Our study also highlighted the impact on patient outcomes following the implementation of ELN guidelines underscores the importance of adherence to standardized protocols in clinical practice.

{"title":"Comprehensive analysis of tyrosine kinase domain mutations and imatinib resistance in chronic myeloid leukemia patients","authors":"Somprakash Dhangar , Chandrakala Shanmukhaiah , Jagdeeshwar Ghatanatti , Leena Sawant , Nehakumari Maurya , Babu Rao Vundinti","doi":"10.1016/j.leukres.2025.107679","DOIUrl":"10.1016/j.leukres.2025.107679","url":null,"abstract":"<div><div>Tyrosine kinase domain mutations (TKDMs) plays an important role in prognosis of chronic myeloid leukemia (CML). The aim of the present study was to identify the TKDMs associated with imatinib mesylate (IM) drug resistant in CML, following European leukemia Net (ELN) guidelines. Direct sequencing analysis revealed point mutations in 69.44 % (50/72), compound/ polyclonal mutations in 11.11 % (8/72) and large deletions in 4.16 % (3/72) of IM non-responder CML patients. Additionally, we have identified low level mutations in 30.55 % of warning group patients through NGS analysis, that include singly occurring point mutations (5) and polyclonal (6) mutations with mutant allele frequency ranging from 1.1 % to 14.70 %. The low-level mutations detected through NGS in warning group patients; may be responsible for suboptimal response in our study. However, follow-up studies are important to understand the mechanism of clonal evolution. We also identified 5 novel mutations that had not been reported in public databases which expands the spectrum of known mutations in <em>BCR::ABL1</em> fusion gene. Our study also highlighted the impact on patient outcomes following the implementation of ELN guidelines underscores the importance of adherence to standardized protocols in clinical practice.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"152 ","pages":"Article 107679"},"PeriodicalIF":2.1,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670305","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}

引用次数: 0

Stratagems of HTLV-1 for persistent infection and the resultant oncogenesis: Immune evasion and clonal expansion

IF 2.1 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2025-03-16 DOI: 10.1016/j.leukres.2025.107680

Takafumi Shichijo, Jun-ichirou Yasunaga

Adult T-cell leukemia-lymphoma (ATL) is one of the most severe malignant T-cell leukemia/lymphomas induced by human T-cell leukemia virus type I (HTLV-1). HTLV-1 persists in the host through stratagems of proliferating infected cells and evading host immunity. HTLV-1 encodes two viral oncogenes, tax and HTLV-1 bZIP factor (HBZ), which are related with protection from cell death and promotion of cell proliferation. In addition, HBZ and the somatic mutations in host genes, such as C-C chemokine receptor 4 (CCR4) and CIC, convert HTLV-1–infected cells into regulatory T (Treg)-like cells, leading to evasion of host immunity. A recent study demonstrated the key mechanisms for clonal expansion of HTLV-1–infected cells; the activation of the transforming growth factor (TGF)-β signaling pathway by HBZ not only converts HTLV-1–infected cells into a Treg-like cells through Foxp3 expression, but also contributes to the proliferation of HTLV-1–infected cells themselves. Due to the longevity induced by HTLV-1 infection, somatic mutations and epigenetic aberrations are accumulated in infected clones, contributing to the oncogenesis of ATL. Collectively, the long-term survival of infected cells enabled by the HTLV-1’s stratagems for persistent infection ultimately leads to ATL oncogenesis via the accumulation of genetic/epigenetic abnormalities.

{"title":"Stratagems of HTLV-1 for persistent infection and the resultant oncogenesis: Immune evasion and clonal expansion","authors":"Takafumi Shichijo, Jun-ichirou Yasunaga","doi":"10.1016/j.leukres.2025.107680","DOIUrl":"10.1016/j.leukres.2025.107680","url":null,"abstract":"<div><div>Adult T-cell leukemia-lymphoma (ATL) is one of the most severe malignant T-cell leukemia/lymphomas induced by human T-cell leukemia virus type I (HTLV-1). HTLV-1 persists in the host through stratagems of proliferating infected cells and evading host immunity. HTLV-1 encodes two viral oncogenes, <em>tax</em> and <em>HTLV-1 bZIP factor (HBZ)</em>, which are related with protection from cell death and promotion of cell proliferation. In addition, <em>HBZ</em> and the somatic mutations in host genes, such as <em>C-C chemokine receptor 4</em> (<em>CCR4)</em> and <em>CIC</em>, convert HTLV-1–infected cells into regulatory T (Treg)-like cells, leading to evasion of host immunity. A recent study demonstrated the key mechanisms for clonal expansion of HTLV-1–infected cells; the activation of the transforming growth factor (TGF)-β signaling pathway by HBZ not only converts HTLV-1–infected cells into a Treg-like cells through <em>Foxp3</em> expression, but also contributes to the proliferation of HTLV-1–infected cells themselves. Due to the longevity induced by HTLV-1 infection, somatic mutations and epigenetic aberrations are accumulated in infected clones, contributing to the oncogenesis of ATL. Collectively, the long-term survival of infected cells enabled by the HTLV-1’s stratagems for persistent infection ultimately leads to ATL oncogenesis via the accumulation of genetic/epigenetic abnormalities.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"152 ","pages":"Article 107680"},"PeriodicalIF":2.1,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143687909","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}

引用次数: 0

Clinical and therapeutic significance of genetic profiling in adult T-cell leukemia/lymphoma

IF 2.1 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2025-02-28 DOI: 10.1016/j.leukres.2025.107676

Yasunori Kogure , Keisuke Kataoka

Adult T-cell leukemia/lymphoma (ATLL) is a highly aggressive T-cell malignancy with a poor prognosis. Several genetic analyses using next-generation sequencing have uncovered recurrent mutations and copy number alterations involved in diverse functional pathways, including T-cell receptor/NF-κB signaling, immune surveillance, transcription factors, chemokine receptors, and CIC-ATXN1 complex. In addition to these alterations, recurrent structural variations, including PD-L1 (CD274) and REL truncations, characterize ATLL genome. Recent clinicogenetic studies have linked several genetic alterations, such as PRKCB mutations, to a worse clinical outcome. Using genetic and clinical factors, novel prognostic models have been developed, which outperform previous models based on only clinical factors in prognostic prediction. Furthermore, genetic and epigenetic events influencing response to molecularly targeted therapies, such as mogamulizumab and valemetostat, have also been identified. Collectively, these insights underscore the clinical importance of assessing genetic alterations. This review highlights the latest insights into the genetic landscape of ATLL and their clinical implications, which will facilitate the development of future strategies for targeted and personalized therapy.

{"title":"Clinical and therapeutic significance of genetic profiling in adult T-cell leukemia/lymphoma","authors":"Yasunori Kogure , Keisuke Kataoka","doi":"10.1016/j.leukres.2025.107676","DOIUrl":"10.1016/j.leukres.2025.107676","url":null,"abstract":"<div><div>Adult T-cell leukemia/lymphoma (ATLL) is a highly aggressive T-cell malignancy with a poor prognosis. Several genetic analyses using next-generation sequencing have uncovered recurrent mutations and copy number alterations involved in diverse functional pathways, including T-cell receptor/NF-κB signaling, immune surveillance, transcription factors, chemokine receptors, and CIC-ATXN1 complex. In addition to these alterations, recurrent structural variations, including <em>PD-L1</em> (<em>CD274</em>) and <em>REL</em> truncations, characterize ATLL genome. Recent clinicogenetic studies have linked several genetic alterations, such as <em>PRKCB</em> mutations, to a worse clinical outcome. Using genetic and clinical factors, novel prognostic models have been developed, which outperform previous models based on only clinical factors in prognostic prediction. Furthermore, genetic and epigenetic events influencing response to molecularly targeted therapies, such as mogamulizumab and valemetostat, have also been identified. Collectively, these insights underscore the clinical importance of assessing genetic alterations. This review highlights the latest insights into the genetic landscape of ATLL and their clinical implications, which will facilitate the development of future strategies for targeted and personalized therapy.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"151 ","pages":"Article 107676"},"PeriodicalIF":2.1,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143561766","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}

引用次数: 0

Outcomes of triple-class refractory multiple myeloma patients at a single clinic: A retrospective study

IF 2.1 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2025-02-28 DOI: 10.1016/j.leukres.2025.107677

Ryan Danis , Sean Bujarski , David Yashar , Ashley Del Dosso , Jonathan Moore , Sarah Mettias , James R. Berenson

Background

Multiple myeloma (MM) is an incurable B cell malignancy requiring complex treatments with a variety of drugs. Patients often become refractory to proteasome inhibitors, immunomodulatory agents, and anti-CD38 monoclonal antibodies (mAb), and termed triple class refractory (TCR), associated with a poor prognosis.

Objective

We performed a retrospective analysis of data regarding the outcomes of TCR MM patients at a single clinic specializing in the care of multiple myeloma patients.

Patients and methods

A retrospective chart review was conducted among 117 patients with TCR MM at a single clinic. Patients’ progression-free survival (PFS), overall survival (OS), cytogenetics, lines of prior therapy (LOT), and first treatment they received after the development of TCR disease were determined.

Results

The median time from diagnosis to development of TCR disease from diagnosis was 47 months (range: 1.5–191.0; n = 104) and the median LOT prior to TCR disease development was 5 (range: 2–13; n = 117). From the development of TCR disease, patients in our study showed a median OS of 18.9 months (range: 0.03–60.0) and a median PFS of 3.1 months (range: 0.1–55.1). The most commonly utilized first treatment regimens used after TCR disease development were mAb-containing combinations (n = 42). Venetoclax-based regimens showed the longest median PFS at 12.4 months (n = 14).

Conclusions

This median OS of 18.9 months recorded at a single clinic provides real-world data regarding the survival of TCR MM patients highlighting the need for improvement in prognosis for this subset of patients.

背景多发性骨髓瘤（MM）是一种无法治愈的B细胞恶性肿瘤，需要使用多种药物进行复杂的治疗。患者常常对蛋白酶体抑制剂、免疫调节剂和抗CD38单克隆抗体（mAb）产生难治性，被称为三类难治性（TCR），预后较差。我们对一家专门治疗多发性骨髓瘤患者的诊所的TCR MM患者的预后数据进行了回顾性分析。结果从诊断到出现TCR疾病的中位时间为47个月（范围：1.5-191.0；n = 104），出现TCR疾病前的中位LOT为5（范围：2-13；n = 117）。从出现 TCR 疾病开始，我们研究中的患者中位 OS 为 18.9 个月（范围：0.03-60.0），中位 PFS 为 3.1 个月（范围：0.1-55.1）。TCR疾病发生后最常用的首次治疗方案是含mAb的组合（n = 42）。基于 Venetoclax 的治疗方案显示出最长的中位 PFS，为 12.4 个月（n = 14）。结论一家诊所记录的中位 OS 为 18.9 个月，这提供了有关 TCR MM 患者生存情况的真实世界数据，强调了改善该亚组患者预后的必要性。

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引用次数: 0

The impact of the solute carrier gene superfamily polymorphisms on tyrosine kinase inhibitors responses among chronic myeloid leukemia: A meta-analysis

IF 2.1 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2025-02-27 DOI: 10.1016/j.leukres.2025.107673

Vu Thi Thuy , Nguyen Linh Viet , Nguyen Trong Nghia , Giovanni Cangelosi , Fabio Petrelli , Cuc Thi Thu Nguyen

Background

Tyrosine kinase inhibitors (TKIs) are currently the first-line therapy for chronic myeloid leukemia (CML), but proportion of treatment responses may be influenced by genetic polymorphisms, especially, the solute carrier gene superfamily (SLC). This study was conducted to evaluate the relationship of polymorphisms in the SLC genes family and treatment responses to TKIs among CML patients.

Methods

A systematic search was conducted from four databases, including PubMed, Cochrane Library, Embase and Web of Science, up to March 2023. The relationship between SLC polymorphisms and TKI efficacy was assessed by pooled odds ratios (ORs) of the complete cytogenetic response (CCyR) and major molecular biological response (MMR) with 95 % confidence intervals (95 %CIs) across five genetic models (dominant, recessive, homozygote, heterozygote, and allele). Meta-analyses, heterogeneity between studies, publication bias, sensitivity, meta-regression and subgroup analysis were all performed.

Results

A total of 19/983 studies meeting the criteria were included in the meta-analysis, with eight variants belonging to three genes (SLC22A1, SLCO1B3, and SLC22A4). The results showed that there was a statistically significant association between the SLC22A1 rs683369 variant and a lower rate of achieving MMR in all 05 genetic models. Similar results were also recorded in the dominant and homozygote models of the SLC22A1 rs628031 variant (OR= 0.61 (95 %CI= 0.46–0.82); OR= 0.46 (95 %CI= 0.23–0.94), respectively); particularly in Asian patients. No relationship was identified between MMR and other genes, as well as that of CCyR and all variants.

Conclusion

SLC variants can be predictive signals of imatinib responses among CML; Asian patients should be paid attention during the treatment.

{"title":"The impact of the solute carrier gene superfamily polymorphisms on tyrosine kinase inhibitors responses among chronic myeloid leukemia: A meta-analysis","authors":"Vu Thi Thuy , Nguyen Linh Viet , Nguyen Trong Nghia , Giovanni Cangelosi , Fabio Petrelli , Cuc Thi Thu Nguyen","doi":"10.1016/j.leukres.2025.107673","DOIUrl":"10.1016/j.leukres.2025.107673","url":null,"abstract":"<div><h3>Background</h3><div>Tyrosine kinase inhibitors (TKIs) are currently the first-line therapy for chronic myeloid leukemia (CML), but proportion of treatment responses may be influenced by genetic polymorphisms, especially, the solute carrier gene superfamily (SLC). This study was conducted to evaluate the relationship of polymorphisms in the SLC genes family and treatment responses to TKIs among CML patients.</div></div><div><h3>Methods</h3><div>A systematic search was conducted from four databases, including PubMed, Cochrane Library, Embase and Web of Science, up to March 2023. The relationship between SLC polymorphisms and TKI efficacy was assessed by pooled odds ratios (ORs) of the complete cytogenetic response (CCyR) and major molecular biological response (MMR) with 95 % confidence intervals (95 %CIs) across five genetic models (dominant, recessive, homozygote, heterozygote, and allele). Meta-analyses, heterogeneity between studies, publication bias, sensitivity, meta-regression and subgroup analysis were all performed.</div></div><div><h3>Results</h3><div>A total of 19/983 studies meeting the criteria were included in the meta-analysis, with eight variants belonging to three genes (SLC22A1, SLCO1B3, and SLC22A4). The results showed that there was a statistically significant association between the SLC22A1 rs683369 variant and a lower rate of achieving MMR in all 05 genetic models. Similar results were also recorded in the dominant and homozygote models of the SLC22A1 rs628031 variant (OR= 0.61 (95 %CI= 0.46–0.82); OR= 0.46 (95 %CI= 0.23–0.94), respectively); particularly in Asian patients. No relationship was identified between MMR and other genes, as well as that of CCyR and all variants.</div></div><div><h3>Conclusion</h3><div>SLC variants can be predictive signals of imatinib responses among CML; Asian patients should be paid attention during the treatment.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"151 ","pages":"Article 107673"},"PeriodicalIF":2.1,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143552149","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}

引用次数: 0

Complementing therapeutic strategies for acute myeloid leukemia: Signaling pathways and targets of traditional Chinese medicine

IF 2.1 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2025-02-26 DOI: 10.1016/j.leukres.2025.107672

Qiaoliang Wu , Lei Zhong , Guibing Zhang , Liying Han , Jing Xie , Yao Xu

Leukemia is a heterogeneous malignant tumor of the hematopoietic system and is characterized by the blockage of differentiation and uncontrolled proliferation of myeloid or lymphoid progenitor cells in the bone marrow and peripheral blood. Currently, intensified chemotherapy regimens and hematopoietic stem cell transplantation (HSCT) are the most common treatment methods for various types of leukemia. However, they are associated with severe side effects and multidrug resistance. Therefore, developing new treatment approaches with sufficient therapeutic effects to eliminate leukemia cells and improve leukemia outcomes selectively is essential. Traditional Chinese Medicine (TCM) has received widespread attention as an alternative treatment for acute myeloid leukemia (AML) because of its multi-component and multi-target characteristics. Increasing evidence suggests that TCM blocks AML progression by regulating various biological processes. Herein, we review the effects of TCM therapies for AML and its potential mechanisms and targets. Our findings will promote further research and improve the clinical application of TCM in treating AML.

{"title":"Complementing therapeutic strategies for acute myeloid leukemia: Signaling pathways and targets of traditional Chinese medicine","authors":"Qiaoliang Wu , Lei Zhong , Guibing Zhang , Liying Han , Jing Xie , Yao Xu","doi":"10.1016/j.leukres.2025.107672","DOIUrl":"10.1016/j.leukres.2025.107672","url":null,"abstract":"<div><div>Leukemia is a heterogeneous malignant tumor of the hematopoietic system and is characterized by the blockage of differentiation and uncontrolled proliferation of myeloid or lymphoid progenitor cells in the bone marrow and peripheral blood. Currently, intensified chemotherapy regimens and hematopoietic stem cell transplantation (HSCT) are the most common treatment methods for various types of leukemia. However, they are associated with severe side effects and multidrug resistance. Therefore, developing new treatment approaches with sufficient therapeutic effects to eliminate leukemia cells and improve leukemia outcomes selectively is essential. Traditional Chinese Medicine (TCM) has received widespread attention as an alternative treatment for acute myeloid leukemia (AML) because of its multi-component and multi-target characteristics. Increasing evidence suggests that TCM blocks AML progression by regulating various biological processes. Herein, we review the effects of TCM therapies for AML and its potential mechanisms and targets. Our findings will promote further research and improve the clinical application of TCM in treating AML.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"151 ","pages":"Article 107672"},"PeriodicalIF":2.1,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143520979","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}

引用次数: 0

Molecular genetic characterization of mixed-phenotype acute leukemia (MPAL) with BCR::ABL1 fusion

IF 2.1 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2025-02-18 DOI: 10.1016/j.leukres.2025.107665

Sophia Shi , Qianghua Zhou , Davidson Zhao , Mojgan Zarif , Cuihong Wei , Hassan Sibai , Hong Chang

Background

Mixed-phenotype acute leukemia with BCR::ABL1 fusion (MPAL^BCR::ABL1), previously known as Philadelphia chromosome-positive mixed phenotype acute leukemia, is a heterogeneous group that is segregated into different subtypes based on WHO-HAEM5. The genetic profile of MPAL^BCR::ABL1 remains poorly defined due to its rarity.

Methods

We conducted a retrospective study of 16 patients with MPAL^BCR::ABL1 and compared their clinical and laboratory profiles to 20 patients with AML^BCR::ABL1.

Results

Compared to patients with AML^BCR::ABL with a median age of 64 years old, patients with MPAL^BCR::ABL1 were significantly younger at a median of 47 years old (P = 0.031) with similar white blood cell (WBC) count, hemoglobin (Hb) count, platelet (PLT) count, lactate dehydrogenase (LDH) levels, and bone marrow blast percentage. MPAL^BCR::ABL1 patients harboured a similar frequency of co-occurring additional cytogenetic abnormalities (ACA) compared to AML^BCR::ABL1 with monosomy 7 (25 %) being the most common ACA in MPAL^BCR::ABL1. The most commonly mutated gene in MPAL^BCR::ABL1 patients was RUNX1 at 45 %. The overall survival (OS) and event-free survival (EFS) between MPAL^BCR::ABL1 and AML^BCR::ABL1 significantly differed, conferring a better prognosis for patients with MPAL^BCR::ABL1.

Conclusion

Our results indicate that adult patients with MPAL^BCR::ABL1 present with younger age and may have better survival outcomes than patients with AML^BCR::ABL1. In addition, our next-generation sequencing (NGS) data indicates that RUNX1 is frequently mutated in B/myeloid MPAL^BCR::ABL1 compared to AML^BCR::ABL1. Future studies are warranted to further elucidate the role of RUNX1 in this disease.

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