Hematology最新文献

Objectives: Several observational studies have suggested an association between sleep traits and leukaemia. This study aimed to determine the causal association between sleep traits and leukaemia using two-sample Mendelian Randomization (MR) analysis.

Methods: Publicly available databases were used to retrieve summary statistics from genome-wide association studies (GWAS) related to sleep traits (UK BioBank) and leukaemia (FinnGen database). Inverse Variance Weighted (IVW) method was utilized for the primary MR analysis. Subsequently, we conducted a reverse MR analysis. Sensitivity analyses and statistical power calculation validated the robustness of the research findings. The Steiger directionality test was employed to ascertain the direction of causality.

Results: Univariable MR identified nominal associations between chronotype and higher risk of acute lymphoblastic leukaemia (OR = 2.15, P = 0.014) and chronic myeloid leukaemia (OR = 1.27, P = 0.016), as well as between short sleep duration and lower lymphoid leukaemia risk (OR = 0.06, P = 0.035). However, none remained significant after FDR correction. Sensitivity analyses revealed no evidence of heterogeneity or horizontal pleiotropy. Adjusting for smoking and BMI in multivariable MR abolished all associations. Colocalization suggested shared genetic variants, but reverse MR indicated a significant effect only from acute lymphoblastic leukaemia to chronotype (P_FDR = 0.0017).

Conclusions: Our MR study found several nominal associations that sleep traits causally influence leukaemia subtypes. Nominal associations were not significant after multiple testing correction, attenuated by adjustment for smoking and BMI, and potentially affected by pleiotropy or reverse causation.

Background and objectives: The phase angle, which is associated with cellular health, has garnered increasing attention as a noninvasive and objective method for nutritional assessment. However, the association between malnutrition and phase angle in patients with acute myeloid leukemia remains unreported. Therefore, this study investigated this association in patients with acute myeloid leukemia and established a cut-off phase angle for identifying malnutrition.

Methods and study design: This cross-sectional study retrospectively analysed the data of 74 inpatients with acute myeloid leukemia (66.21% male; mean age, 52.68 ± 16.31 years). Nutritional status was assessed via the Patient-Generated Subjective Global Assessment (PG-SGA). Bioelectrical impedance analysis was employed to measure phase angles.

Results: The phase angle was negatively associated with malnutrition (B = -0.436; p < 0.001). Logistic regression analysis revealed that a low skeletal muscle index (SMI) (p = 0.016, OR = 5.021, 95% CI 1.347-18.716) and hemoglobin deficiency (p = 0.009, OR = 6.133, 95% CI 1.582-23.770) were risk factors for a low phase angle (PA) in acute myeloid leukemia inpatients. The area under the receiver operating characteristic (ROC) curve was 0.705. The cut-off phase angle for identifying malnutrition was 3.65° (sensitivity, 0.926; specificity, 0.553).

Conclusions: The phase angle may serve as a supplementary indicator of malnutrition in inpatients with acute myeloid leukemia, particularly when the Nutritional Risk Screening 2002 (NRS-2002) is not feasible. These findings may aid in the formulation of nutritional strategies for these patients.

Background: B-cell acute lymphoblastic leukemia (B-ALL) is an aggressive hematological malignancy. Long non-coding RNAs (lncRNAs) play important roles in hematological diseases; nevertheless, their mechanistic contributions to B-ALL are still poorly defined.

Purpose: This study aimed to investigate the oncogenic role of HOTAIR and the regulatory mechanism underlying the progression of B-ALL via the HOTAIR/miR-326/IGF-1R axis.

Methods: The expression levels of HOTAIR and miR-326 were quantified by RT-qPCR in peripheral blood mononuclear cells (PBMCs) from B-ALL patients. CCK-8, EdU, and TUNEL assays were employed to evaluate cell viability, proliferation, and apoptosis, respectively. Dual-luciferase reporter assays were performed to verify molecular interactions, and Western blotting was performed to detect the activation of the PI3K/AKT signaling pathway.

Results: HOTAIR was prominently upregulated in patient-derived PBMCs, correlating with enhanced proliferation and suppressed apoptosis. Mechanistically, HOTAIR directly targeted miR-326 binding sites and regulated the expression of IGF-1R. Experiments affirmed that overexpression of miR-326 or knockdown of IGF-1R reversed the oncogenic effects induced by HOTAIR. Furthermore, silencing of HOTAIR decreased PI3K/AKT phosphorylation, indicating pathway dependence.

Conclusion: HOTAIR promotes the progression of B-ALL via the miR-326/IGF-1R axis and PI3K/AKT activation, suggesting its potential as a therapeutic target.

Objective: This review aims to summarize current progress in targeted therapy for acute myeloid leukemia (AML) with KMT2A rearrangement (KMT2Ar). This subtype of AML often shows resistance to chemotherapy and has a poor prognosis. The purpose is to emphasize potential therapeutic strategies and explore drugs currently under clinical development. Methods: We reviewed studies on the molecular characteristics of KMT2Ar AML and examined targeted drugs that can block key genetic and epigenetic mechanisms. Information on drug mechanisms, preclinical findings, and clinical trials was collected and analyzed.

Results: Several new agents targeting KMT2A-related pathways are being explored. Menin inhibitors show encouraging clinical activity, while other inhibitors, such as those targeting DOT1L, BET, and EZH2, have produced promising preclinical results. Early data suggest that combination therapy may be more effective in overcoming drug resistance than monotherapy.

Discussion: Providing a new therapeutic direction for the abnormal molecular networks in KMT2Ar AML offers a promising approach. However, most therapies are still in the early stages and clinical translation is limited. Further research is needed to improve the safety and long-term efficacy of the treatment.

Conclusion: There is an urgent need for effective targeted drugs for KMT2Ar AML. Continuous research and clinical trials will be key to improving patient prognosis and advancing precise treatment for this challenging leukemia subtype.

Objectives: To investigate the clinical significance of Fluorescence in situ hybridization (FISH) in detecting aberration of chromosome 5, 7, or 17 in newly diagnosed acute myeloid leukemia (AML) patients.

Methods: We retrospectively evaluated the clinical features and outcomes of 77 adult newly diagnosed AML patients with 5/5q, 7/7q, or 17/17p loss detected by either FISH or conventional karyotype.

Results: Among 77 patients, all (100%) were identified by FISH, while only 47 (61%) were positive with conventional karyotype. Patients with FISH-positive displayed similar age at onset, gender, WBC, and gene mutation spectrum with those identified by karyotype. In FISH-positive but karyotype-negative group, the 3-year OS and EFS were 28.9% and 23.9%, respectively, which were similar to 29.1% and 21% with FISH-positive and karyotype-positive (P = 0.59 and 0.48). When comparing the outcomes of patients with or without hematopoietic stem cell transplantation (HSCT), both groups of patients with and without HSCT showed similar outcomes. Patients underwent HSCT with 3-year OS at 76.2% in FISH and 64.3% in FISH-positive and karyotype-positive group (P = 0.66), while patients without HSCT had 3-year OS at 33.3% and 39% (P = 0.63), respectively.

Conclusion: Overall, patients with 5, 7, or 17 chromosomal abnormalities identified by either FISH or karyotype have similar clinical characteristics and outcomes. FISH could supplement to conventional karyotype for detecting aberration of chromosome 5, 7, or 17 in newly diagnosed AML.

Introduction: Blood is vital for life, but ensuring a safe and sufficient supply remains a public health challenge, particularly in low-resource settings. This study explores the knowledge, attitudes, practices, and factors influencing blood donation among pre-service teacher trainees at Finote Selam College of Education, Northwest Ethiopia.

Methods: A cross-sectional survey was conducted using proportionate sampling. Data were collected through questionnaires completed by the participants themselves and analyzed using SPSS version 27, with results presented in descriptive narratives and tables.

Results: Of 277 participants, 27.8% were male and 72.2% female. While 55.6% demonstrated adequate knowledge of blood donation and 42.2% had a positive attitude, only 28.2% had ever donated blood. Key factors influencing donation practices included knowledge, attitude, academic department, and religious affiliation.

Conclusion: Although participants had reasonable knowledge of blood donation, positive attitudes and actual donation rates were low. Department-specific awareness programs and regular donation drives, in partnership with health institutions, could enhance donation rates and foster social responsibility among future educators.

Objectives: Prior research has highlighted immune cells' critical role in multiple myeloma (MM) pathogenesis, yet the causal relationships between them have remained obscure.

Methods: We utilized data from genome-wide association studies (GWAS) of European cohorts to conduct a Mendelian Randomization (MR) analysis, aiming to establish causal links between immune cell phenotypes and MM. We selected single nucleotide polymorphisms (SNPs) associated with immune cell traits at a suggestive significance threshold (P < 1 × 10^-5) to ensure sufficient instrumental variables, with F-statistics (>10) calculated to assess instrument strength. Multiple MR methods were applied to 731 immune phenotypes and MM.

Results: Eight immunophenotypes showed nominal associations with MM risk (P < 0.05). However, no associations survived the strict Bonferroni correction for multiple testing. Suggestive causal effects of MM on immunophenotypic traits are predominantly negative, implying that MM may impair the functionality of immune cells.

Discussion: This study uses GWAS data to elucidate the genetic impact of immune cells on the initiation and progression of MM. It presents genetic evidence suggesting that immune cells could alter MM risk based on a thorough genetic analysis. Bidirectional two-sample MR identified eight distinct immunophenotypes (encompassing four immune signatures: MFI, RC, AC, MP) with causal effects on MM.

Conclusion: Our study provides preliminary evidence for potential causal links between specific immune traits and MM risk. Independent replication in larger cohorts and functional validation are warranted given the nominal significance of these associations, which may inform future immunotherapeutic investigations. These findings contribute to a better understanding of the complex immune - MM interplay and may guide future investigations into immunotherapeutic approaches.

Objectives: This study aimed to compare clinical, and molecular features between acute myeloid leukemia (AML) patients aged <50 and ≥50 years, while also assessing their respective treatment outcomes and prognostic factors.

Methods: We conducted a retrospective analysis of clinical data from AML patients treated at our institution between October 2015 and June 2021, supplemented by data extracted from the SEER database spanning 2000 to 2019. Survival outcomes were evaluated using Kaplan-Meier methodology.

Results: In patients aged ≥50 years, we observed higher prevalence of DNMT3A, IDH2, and TP53 mutations along with -5/del (5q) karyotype abnormalities. The treatment outcomes were suboptimal, with a complete response (CR) rate of 45.9%, relapse rate of 60.8%, and two-year overall survival (OS) rate of 33.3%. VEN-treated chemotherapy-intolerant patients showed significantly improved two-year OS (36.0% vs 12.1% in non-VEN group; P = 0.006). In contrast, patients aged <50 years exhibited a distinct molecular profile characterized by a predominance of NRAS, biallelic CEBPA, WT1, and C-KIT mutations, along with a higher incidence of RUNX1-RUNX1T1 and CBFB-MYH11 fusion genes. This group demonstrated more favorable clinical outcomes, with a CR rate of 73.1%, relapse rate of 36.8%, and two-year OS rate of 68.3%.

Conclusions: This study revealed that patients aged ≥50 years displayed more complex genetic aberration profiles and experienced significantly poorer prognoses compared to their younger counterparts. These findings provided novel insights for optimizing treatment strategies for middle-aged and elderly AML patients in the Chinese population.

Objective: To identify simple clinical predictors of prognosis in multiple myeloma (MM) after chemotherapy and assess their predictive value.

Methods: We retrospectively analyzed 164 newly diagnosed MM patients treated with proteasome inhibitor- and/or immunomodulatory drug-based chemotherapy between 2018 and 2024. Baseline data included demographics, DS/ISS stage, haemoglobin (Hb), platelets, albumin, creatinine, calcium, lactate dehydrogenase (LDH), erythrocyte sedimentation rate, and serum β2-microglobulin (β2-MG). Treatment responses after four cycles (CR/VGPR vs ≤PR) and survival outcomes were recorded. Overall survival (OS) and progression-free survival (PFS) were estimated by Kaplan-Meier analysis. Cox models identified independent prognostic factors. Landmark 2-year ROC curves evaluated discriminative ability.

Results: After four cycles, 95/164 patients (57.9%) achieved CR/VGPR and 69 (42.1%) ≤PR. During a median follow-up of 31 months, 85 deaths and 112 progression events occurred. Multivariable analysis showed that age >60 years, Hb ≤85 g/L, β2-MG>3.5 mg/L, and ≤PR were independently associated with shorter OS, whereas Hb ≤85 g/L and ≤PR predicted shorter PFS. Two-year AUCs for mortality prediction were 0.601 for age, 0.624 for Hb, 0.647 for β2-MG, and 0.731 for response; for PFS prediction, AUCs were 0.668 for Hb and 0.749 for response, indicating fair but limited standalone discrimination.

Conclusion: Advanced age, severe anaemia, elevated β2-MG, and suboptimal early response are simple, readily available predictors of adverse survival in MM. Although their individual discriminative power is modest, these factors may inform pragmatic risk stratification, especially where cytogenetic and MRD testing are unavailable, and could be incorporated into future composite prognostic scores.

Background: Bone disease (MBD) is common in patients with multiple myeloma (MM) and ~80% are already affected at diagnosis. MBD increases the risk of skeletal-related events (SREs) and the use of bone-targeted agents (BTAs) is recommended for their prevention and treatment.

Methods: This study retrospectively analyzed electronic health records of adults with MBD treated in real-world practice in any of eight hematology clinics in Bulgaria. The study assessed patients' demographics and clinical characteristics, BTA treatment patterns and pain management, and estimated the incidence of SREs and osteonecrosis of the jaw (ONJ).

Results: The study included 732 patients (denosumab: 177; zoledronic acid: 440; zoledronic acid and denosumab sequentially: 115). In 83%, 84%, and 84% of patients, respectively, the first recorded therapy contained a BTA either alone or in combination with an anti-myeloma therapy. The median (Q1, Q3) duration of BTA administration was longer in patients receiving both BTAs sequentially (zoledronic acid: 84 [24, 157] days; denosumab: 60 [0, 197] days). BTAs were prescribed mostly in preventive intent: only 22%, 16%, and 30%, respectively, had experienced previous SREs. While receiving BTAs, new SREs occurred in 9%, 7%, and 9%, respectively. Seven cases of ONJ were identified but only one occurred during BTA use (in the zoledronic acid cohort).

Conclusions: Patients with MM are at very high risk of SREs. When receiving BTAs with a preventive intent, only a minority (<10%) experienced an SRE. These data suggest that preventive BTA use, effectively reduces the risk of SREs in real-life clinical practice.