Hematology最新文献

{"title":"Reassessing blood product irradiation in haploidentical transplantation: a single-center perspective.","authors":"Juan Pablo Martínez-Hernández, Yesica A López-Mora, Rosario Salazar-Riojas, Dalila Marisol Alvarado Navarro, Ana Karen Hernández-Navarro, Yair Omar Chavez-Estrada, Andrés Gómez-De León, Cesar Homero Gutierrez-Aguirre, Perla R Colunga-Pedraza, Olga Graciela Cantú-Rodríguez, José Carlos Jaime-Pérez, David Gomez-Almaguer","doi":"10.1080/16078454.2024.2420144","DOIUrl":"https://doi.org/10.1080/16078454.2024.2420144","url":null,"abstract":"<p><strong>Objectives: </strong>The main objective was to investigate the incidence of transfusion-associated graft-versus-host disease (TA-GVHD) in patients who underwent haploidentical hematopoietic cell transplants (HCT) and received non-irradiated leukoreduced blood components. The secondary objective was to describe our leukodepletion results in blood products obtained by the filters employed at our center.</p><p><strong>Study design and methods: </strong>Clinical records from 2018 to 2023 were retrospectively analyzed, along with a prospective evaluation of residual leukocytes in blood components from June to November 2023 in order to confirm effectivity of our leukodepletion method.</p><p><strong>Results: </strong>150 patients were included, no cases of TA-GVHD were reported after using non-irradiated blood products. The incidence of grade 3-4 acute and moderate-severe chronic GVHD was 12.7% (n = 19) and 2.7% (n = 4), respectively. The cumulative incidence of death was 39.3% (n = 52) with a 3.7-year overall survival (CI 95%, 3.3- 4.1 years). Leukodepletion analysis showed a reduction of 99.93% in platelet concentrates and 99.98% in packed red blood cells.</p><p><strong>Discussion: </strong>TA-GVHD in HCT remains a concern traditionally mitigated using blood product irradiation. Recent evidence obtained in favor of leukoreduction techniques question this need, especially in resource-limited settings.</p><p><strong>Conclusion: </strong>These findings support leukoreduction as a primary TA-GVHD preventive measure,along with the advantage in cost reduction.</p>","PeriodicalId":13161,"journal":{"name":"Hematology","volume":"29 1","pages":"2420144"},"PeriodicalIF":2.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142499424","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":"Efficacy of daratumumab on multiple myeloma patients with renal insufficiency: a systematic review and meta-analysis.","authors":"Hua Jiang, Lu Li, Meiyu Guo, Meizhang Li, Hao Wu, Xiaomei Chen, Mingzhao Gao, Qianqian Xu, Jia Mi, Canchan Cui, Weijun Fu","doi":"10.1080/16078454.2024.2399430","DOIUrl":"10.1080/16078454.2024.2399430","url":null,"abstract":"<p><strong>Background: </strong>Renal insufficiency (RI) is a key factor affecting the prognosis of multiple myeloma (MM) patients. Because the benefit of daratumumab for treating MM patients with RI remains unclear, our objective was to evaluate the efficacy of daratumumab on MM patients with RI.</p><p><strong>Methods: </strong>We conducted a systematic search of the PubMed, EMBASE, and Cochrane Library databases as of October 24, 2023. Two independent reviewers screened the article titles, abstracts, and full text to identify the randomized controlled trials (RCTs) meeting the inclusion and exclusion criteria. Meta-analyses were performed using RevMan version 5.4. Outcomes of interest were progression-free survival (PFS), overall survival (OS), complete response or better (≥CR), and minimal residual disease (MRD) negativity, all calculated as hazard ratios (HRs) or risk ratios (RRs) with 95% confidence intervals (CIs).</p><p><strong>Results: </strong>A total of 10 RCTs with 5003 patients were included. Add-on daratumumab improved PFS and OS among newly diagnosed MM (NDMM) patients with RI (HR 0.48 [95% CI: 0.36, 0.64, I2 = 65%] and HR 0.63 [95% CI: 0.48, 0.82, I2 = 0%]) as well as relapsed/refractory MM (RRMM)-RI patients, compared with the control group (HR 0.46 [95% CI: 0.37, 0.58, I2 = 0%] and HR 0.68 [95% CI: 0.51, 0.92, I2 = 0%]). In terms of the renal status, the efficacy of add-on daratumumab for MMRI patients was similar to that for MM patients with normal renal function. A prolonged PFS benefit for add-on daratumumab treatment versus the control was evident across all RRMM-RI subgroups, and the benefits tended to increase with the follow-up time.</p><p><strong>Conclusions: </strong>Our results indicate that MM patients with RI could benefit from a daratumumab-added regimen regardless of MM status. Additional high-quality RCTs are still warranted to confirm our findings.</p>","PeriodicalId":13161,"journal":{"name":"Hematology","volume":"29 1","pages":"2399430"},"PeriodicalIF":2.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142153886","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":"Function of NLRP3 inflammasome activation in multiple myeloma.","authors":"Xiaorong Zhu, Jie Yu, Mingqiang Hua, Ning Xu, Lianjuan Wang, Lingkai Chen, Yanhong Jia, Xueyun Zhao","doi":"10.1080/16078454.2024.2399367","DOIUrl":"10.1080/16078454.2024.2399367","url":null,"abstract":"<p><strong>Objective: </strong>The drug resistance of multiple myeloma (MM) cells is one of the main causes of relapse, refractory and progression of MM.</p><p><strong>Methods: </strong>First, Western blot analysis was used to detect the expression levels of NLRP3, ASC, pro-IL-1β and cleaved IL-1β, and RT-qPCR was used to detect the mRNA expression levels of them. The expression levels of IL-1β and IL-18 in the supernatant were detected by ELISA, and the expression levels of these factors in the activated group and the control group were compared to verify the activation of BMMCs and KM3.</p><p><strong>Result: </strong>1. The protein expression of NLRP3 and cleavd-IL-1β in the BMMCs cells was significantly higher than that of the control group (<i>P </i>< 0.05). The mRNA expression levels of caspase-1 and IL-1β were higher than those of the control group (<i>P </i>= 0.03, <i>P </i>= 0.02). 2. The protein expression levels of NLRP3 and cleaved-IL-1β in the KM3 cells were significantly higher than those of the control group (<i>P </i>< 0.05). The expressions of caspase-1 mRNA(<i>P </i>= 0.016) and IL-1β mRNA(<i>P </i>= 0.037) were significantly increased compared with the control group. 3. The early apoptosis results of BMMCs showed that the apoptosis rate of the LPS+ATP+Dex group was lower than that of the Dex group (<i>P </i>= 0.017). The early apoptosis rate of the LPS+ATP+Dex+Vel group was decreased compared with the Dex+Vel group (<i>P </i>= 0.045). 4. The early apoptosis rate of KM3 in the LPS+ATP+Dex group was lower than that in the Dex group (<i>P </i>= 0.03).</p><p><strong>Conclusion: </strong>1. LPS+ATP can activate NLRP3 inflammasome in multiple myeloma cells. 2. Activation of NLRP3 inflammasome inhibits the early apoptosis of myeloma cells induced by dexamethasone and bortezomib.</p>","PeriodicalId":13161,"journal":{"name":"Hematology","volume":"29 1","pages":"2399367"},"PeriodicalIF":2.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142286013","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":"Extracellular vesicle-mediated regulation of imatinib resistance in chronic myeloid leukemia via the miR-629-5p/SENP2/PI3K/AKT/mTOR axis.","authors":"Yaqin Jiang, Shishan Xiao, Shengwen Huang, Xuemei Zhao, Siruiyun Ding, Qianqian Huang, Wei Xiao, Zhe Li, Hongqian Zhu","doi":"10.1080/16078454.2024.2379597","DOIUrl":"10.1080/16078454.2024.2379597","url":null,"abstract":"<p><strong>Background: </strong>Imatinib (IM) is the primary treatment for patients with chronic-phase CML (CML-CP). However, an increasing number of CML-CP patients have developed resistance to IM. Our study aims to explore the expression of miR-629-5p in extracellular vesicles (EVs) from both IM-sensitive (K562) and resistant (K562-Re) CML cell lines and to investigate the impact of regulating miR-629-5p expression on the biological characteristics of K562 and K562-Re cells.</p><p><strong>Methods: </strong>Assess miR-629-5p expression levels in IM-sensitive and resistant CML cell lines. Separate EVs and verify it. EVs from K562-Re cells were co-cultured with K562 cells to detect the expression level of miR-629-5p. Target genes of miR-629-5p were determined and validated through luciferase experiments. Examined by manipulating miR-629-5p expression in cells using transfection techniques. The expression level of phosphorylated proteins in the PI3K/AKT/mTOR signaling pathway after IM was detected in CML cell lines. In K562-Re cells, the expression level of phosphorylated protein in the PI3K/AKT/mTOR signaling pathway was detected after single transfection of miR-629-5p inhibitor and cotransfection of miR-629-5p inhibitor and siSENP2.</p><p><strong>Results: </strong>Increasing concentrations of EVs from K562-Re cells elevated miR-629-5p expression levels. The expression levels of miR-629-5p in CML cells varied with IM concentration and influenced the biological characteristics of cells. SENP2 was identified as a target gene of miR-629-5p. Furthermore, miR-629-5p was found to modulate the SENP2/PI3K/AKT/mTOR pathway, impacting IM resistance in CML cells.</p><p><strong>Conclusion: </strong>EVs from IM-resistant CML cells alter the expression of miR-629-5p in sensitive cells, activating the SENP2/PI3K/AKT/mTOR pathway and leading to IM resistance.</p>","PeriodicalId":13161,"journal":{"name":"Hematology","volume":"29 1","pages":"2379597"},"PeriodicalIF":2.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141758417","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":"<i>HbA2</i>:c.96-2A > G mutation: report of 7 cases in China.","authors":"Xiao-Hua Yu, Yi-Yuan Ge, Xiao-Min Ma, Guang-Kuan Zeng, Yu-Wei Liao, Li-Li Liu, Yan-Bin Cao, Jian-Lian Liang, Bai-Ru Lai, Yan-Qing Zeng, Yu-Chan Huang, Li-Ye Yang","doi":"10.1080/16078454.2024.2426829","DOIUrl":"https://doi.org/10.1080/16078454.2024.2426829","url":null,"abstract":"<p><strong>Objective: </strong>To analyze the hematological phenotype and genotype of <i>HbA2</i>: c.96-2A > G carriers.</p><p><strong>Methods: </strong>The blood routine parameters and hemoglobin electrophoresis of rare cases were analyzed and identified by PCR combined with reverse dot blot (RBD-PCR), GAP-PCR and DNA sequencing.</p><p><strong>Results: </strong>Among the 7 patients, one adult patient had normal hemoglobin levels, with slightly decreased mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH). Hb Bart's band was found in 6 neonates by hemoglobin electrophoresis, of which the content of Hb Bart's band in 1 neonate was 15.80%, and the content of Hb Bart's band in the other 5 neonates was 0.30%-0.90%. The results of genetic analysis showed that all the 7 patients had <i>HbA2</i>: c.96-2A > G (IVS-I-116A > G) mutation, in which 1 case was compounded with - ^SEA deletion.</p><p><strong>Conclusion: </strong><i>HbA2</i>: c.96-2A > G mutation carriers exhibit the phenotype of α-thalassemia, and when the <i>HbA2</i>:c.96-2A > G mutation is combined with - ^SEA deletion, an intermediate phenotype of anemia is produced.</p>","PeriodicalId":13161,"journal":{"name":"Hematology","volume":"29 1","pages":"2426829"},"PeriodicalIF":2.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619254","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":"Successful eradication of acquired factor VIII inhibitors with rituximab: a report of two cases.","authors":"Main Atallah Mohammed Abumahfouz, Anas Al-Sadi, Awni Alshurafa, Israa Jawarneh, Ruba Y Taha, Sarah A Elkourashy","doi":"10.1080/16078454.2024.2424521","DOIUrl":"https://doi.org/10.1080/16078454.2024.2424521","url":null,"abstract":"<p><strong>Objectives: </strong>Acquired hemophilia A (AHA) is a rare autoimmune disorder that presents with spontaneous bleeding due to the development of autoantibodies against coagulation factor VIII. This study aims to highlight the challenges in diagnosing and treating AHA, particularly through presenting two cases managed with rituximab, an anti-CD20 antibody, to demonstrate its safety and efficacy as a treatment option.</p><p><strong>Methods: </strong>Two male patients, aged 38 and 68, with significant bleeding episodes and prolonged activated partial thromboplastin time (aPTT), were evaluated. Both patients received standard care, including factor VIII replacement and corticosteroids. Due to persistent symptoms, rituximab was administered weekly for four weeks, and follow-up assessments were performed to monitor factor VIII levels, aPTT, and clinical symptoms.</p><p><strong>Results: </strong>Both cases showed improvement with rituximab. In Case 1, a 38-year-old male with idiopathic AHA achieved normal factor VIII levels and aPTT, with complete resolution of symptoms and no recurrence. In Case 2, a 68-year-old male with congenital hemophilia A and superimposed AHA responded positively to rituximab, showing stabilized factor VIII levels and no further bleeding episodes at a six-month follow-up.</p><p><strong>Discussion: </strong>The management of AHA is complex due to its rarity and severe bleeding risks. Although corticosteroids and bypassing agents are primary treatments, rituximab is emerging as a promising therapeutic option. Current literature supports rituximab for patients with contraindications to first-line agents or poor prognosis, yet further studies are required to assess its potential as a first-line treatment.</p><p><strong>Conclusion: </strong>These cases emphasize the efficacy and safety of rituximab in managing AHA. Given its potential benefits, further randomized controlled trials are warranted to evaluate rituximab's role as a first-line treatment. A structured monitoring protocol is recommended to ensure safe administration and manage potential side effects associated with immunosuppressive therapy.</p>","PeriodicalId":13161,"journal":{"name":"Hematology","volume":"29 1","pages":"2424521"},"PeriodicalIF":2.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142619261","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":"Prognosis influence of additional chromosome abnormalities in newly diagnosed acute promyelocytic leukemia with t(15;17)(q24;q21).","authors":"Lin Liu, Jinghan Wang, Huan Xu, Shuqi Zhao, Lu Wang, Jiansong Huang, Huanping Wang, Hongyan Tong, Jie Jin","doi":"10.1080/16078454.2023.2293513","DOIUrl":"10.1080/16078454.2023.2293513","url":null,"abstract":"<p><strong>Objectives: </strong>In patients with acute promyelocytic leukemia (APL), additional chromosomal abnormalities (ACAs) are prognostic indicators. However, the clinical features of ACAs were not systematically reported in Chinese patients. Therefore, we enrolled a large cohort of APLs to demonstrate the clinical characteristics and prognostic value of ACAs.</p><p><strong>Methods: </strong>268 patients with newly diagnosed APL with t(15;17)(q24;q21) were retrospectively enrolled, and their clinical characteristics and the predictive value of ACAs were assessed between patients with the presence and absence of ACAs.</p><p><strong>Results: </strong>APL patients with and without ACAs did not differ significantly in their clinical features or treatment response and clinical outcomes like overall survival (OS) and disease-free survival (DFS). It appeared to be substantially associated with worse OS in APL patients with trisomy 8, which was the most common ACA, although DFS was unaffected. Interestingly, the presence of ACAs or trisomy 8 affected OS and DFS in the subgroup of patients aged ≥60 years; by contrast, ACAs had no effect on OS or DFS in any treatment subgroup (ATRA + ATO/RIF or ATRA + ATO/RIF + CH or ATRA + CH), except for the ATRA + ATO/RIF + CH treatment subgroup, where their impact on DFS was less favorable.</p><p><strong>Conclusions: </strong>Our results suggested that OS and DFS were unaffected by ACAs. Nonetheless, in the subgroup of patients older than 60, the existence of ACAs or trisomy 8 appeared to impact OS and DFS negatively. Individuals with t(15;17) alone had a higher DFS and were more susceptible to ATRA + ATO/RIF + CH than individuals with t(15;17) ACAs.</p>","PeriodicalId":13161,"journal":{"name":"Hematology","volume":"29 1","pages":"2293513"},"PeriodicalIF":1.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139039815","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":"PHF19 before and post induction treatment possess favorable potency of reflecting treatment response to protease inhibitors, event-free survival, and overall survival in multiple myeloma patients.","authors":"Hongyu An, Shiming Chen, Xin Zhang, Shandong Ke, Jinyong Ke, Yalan Lu","doi":"10.1080/16078454.2024.2331389","DOIUrl":"10.1080/16078454.2024.2331389","url":null,"abstract":"<p><strong>Objective: </strong>Plant homeodomain finger protein 19 (PHF19) regulates hematopoietic stem cell differentiation and promotes multiple myeloma (MM) progression. This study intended to explore the potency of PHF19 at baseline and post induction treatment in estimating treatment response to protease inhibitors and survival in MM patients.</p><p><strong>Methods: </strong>This retrospective study screened 69 MM patients who received protease inhibitors with bone marrow (BM) samples available at both baseline and post induction treatment. Twenty healthy BM donors were included as healthy controls (HCs). PHF19 in plasma cells from BM was quantified by reverse transcription-quantitative polymerase chain reaction.</p><p><strong>Results: </strong>PHF19 at baseline and post induction treatment in MM patients were increased than in HCs. In MM patients, PHF19 was declined post induction treatment. Elevated PHF19 at baseline and post induction treatment were correlated with renal impairment, beta-2-microglobulin ≥5.5 mg/L, <i>t</i> (4; 14), higher international staging system (ISS) stage, and higher revised ISS (R-ISS) stage. Concerning treatment response, PHF19 at baseline and post induction treatment were negatively associated with complete response and overall response rate. Notably, abnormal PHF19 (above 95% quantile value of PHF19 in HCs) at baseline and post induction treatment were linked with shortened event-free survival (EFS) and overall survival (OS). After adjustment, abnormal PHF19 post induction treatment was independently related to shortened EFS (hazard ratio = 2.474) and OS (hazard ratio = 3.124).</p><p><strong>Conclusion: </strong>PHF19 is aberrantly high and declines post induction therapy, which simultaneously reflects unfavorable treatment response to protease inhibitors as well as shorter EFS and OS in MM patients.</p>","PeriodicalId":13161,"journal":{"name":"Hematology","volume":"29 1","pages":"2331389"},"PeriodicalIF":1.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140174454","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":"Prevalence of thalassaemia among childbearing-age Li and Han populations in Hainan Province.","authors":"Fangchao Tao, Yanquan Lai, Jiaqi Chen, Shijie Wei, Yu Zou, Yunli Lai, Qiongzhen Qin, Yufeng Wang, Wanjun Zhou","doi":"10.1080/16078454.2024.2417524","DOIUrl":"10.1080/16078454.2024.2417524","url":null,"abstract":"<p><strong>Objectives: </strong>Accurate epidemiological data are crucial for effective disease prevention and treatment. We conducted a large-scale survey to explore the thalassaemia prevalence and spectrum among the two major ethnic groups in Hainan Province.</p><p><strong>Methods: </strong>A total of 399,053 childbearing-age individuals of Li (<i>n </i>= 77,563) and Han(<i>n </i>= 321,490) ethnic groups were recruited from 18 cities and counties in Hainan, and their thalassemia genotypes were systematically screened and statistically analysed.</p><p><strong>Results: </strong>This study revealed a significantly higher thalassaemia carrier rate in the Li (55.39%) than that in the Han (13.13%). Specifically, the carrier rate of α-thalassaemia was 46.39% in the Li and 10.02% in the Han. The predominant α-thalassaemia mutations were - <i>α^3.7</i> and - <i>α^42.</i> in Li, whereas the main mutation were - <i>^SEA</i> and - <i>α^4.2</i> in Han. For β-thalassaemia, the carrier rates were 1.68% in Li and 2.38% in Han, with <i>CD41-42(-CTTT)</i> the most prevalent mutation in both groups. The carrier rates of β-/α-compound thalassaemia were 7.32% in Li and 0.73% in Han. Additionally, there were regional differences in the distribution of thalassemia among the Li and Han within Hainan Province.</p><p><strong>Conclusion: </strong>Epidemiological characteristics and molecular spectrum of thalassaemia among the Li and Han ethnic groups in Hainan were revealed in this study. These findings can provide a scientific basis to develop and implement prevention strategies for thalassaemia in Hainan.</p>","PeriodicalId":13161,"journal":{"name":"Hematology","volume":"29 1","pages":"2417524"},"PeriodicalIF":2.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142464131","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":"Variation characteristics and clinical significance of <i>TP53</i> in patients with myeloid neoplasms.","authors":"Qiang Ma, Yan Liu, Hong Zhao, Yixian Guo, Wanling Sun, Ronghua Hu","doi":"10.1080/16078454.2024.2387878","DOIUrl":"https://doi.org/10.1080/16078454.2024.2387878","url":null,"abstract":"<p><p><b>Objectives:</b> MDS and AML characterized by <i>TP53</i> variations have a poor prognosis in general. However, specifically, differences in prognosis have also been observed in patients with different <i>TP53</i> variants and VAFs.<b>Methods:</b> Here, we retrospectively analyzed datasets of patients with MDS, MPN, and AML who underwent targeted DNA sequencing from February 2018 to December 2023, and patients with reportable <i>TP53</i> variations were screened. Demographic data and clinical data were collected, and the relationship between <i>TP53</i> alterations and patient prognosis (AML/MDS) was analyzed using the cBioPortal and Kaplan-Meier Plotter databases. The relationship between the VAFs of <i>TP53</i> variations and prognoses was analyzed using data from the present study.<b>Results:</b> Sixty-two variants of <i>TP53</i> were identified in 58 patients. We mainly identified single mutations (79.31%, 46/58), followed by double (17.24%, 10/58) and triple (3.45%, 2/58) mutations. The variations were mainly enriched in exon4-exon8 of <i>TP53</i>. Missense (72.58%, 45/62) mutations were the main type of variations, followed by splice-site (9.68%, 6/62), nonsense (9.68%, 6/62), frameshift (6.45%, 4/62), and indel (1.61%, 1/62) mutations. In this study, p.Arg175His and p.Arg273His were high-frequency <i>TP53</i> mutations, and <i>DNMT3A</i> and <i>TET2</i> were commonly co-mutated genes in the three types of myeloid neoplasms; However, we reported some new <i>TP53</i> variants in MPN that have not been found in the public database. Moreover, MDS or AML characterized by altered <i>TP53</i> had a shorter OS than patients in the unaltered group (<i>P</i><0.01), low <i>TP53</i> mRNA levels were associated with shorter OS in patients with AML (<i>P</i><0.01). Data from our center further found higher VAF (≥10%) associated with shorter OS in patients with MDS (median 2.75 vs. 24 months) (<i>P</i><0.01).<b>Conclusion:</b> <i>TP53</i> mutations are mainly enriched in exon4-exon8, are missense and single mutations in myeloid neoplasms, and are associated with poor prognosis of MDS/AML, and higher VAF (≥10%) of <i>TP53</i> mutations associated with a shorter OS in patients with MDS.</p>","PeriodicalId":13161,"journal":{"name":"Hematology","volume":"29 1","pages":"2387878"},"PeriodicalIF":2.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141975548","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}