Blood Research最新文献

The phosphatidylinositol-3-kinase/AKT/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway and microRNA (miRNA) regulation have been implicated in the initiation and progression of acute leukemia. Despite significant progress in the understanding of leukemogenic mechanisms, current therapies remain limited by relapse, drug resistance, and poor long-term survival, underscoring the need for novel targeted strategies. This review provides the current evidence regarding the molecular interplay between PI3K/AKT/mTOR signaling and miRNA dysregulation in acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). We highlight key oncogenic and tumor-suppressive miRNAs, discuss their regulatory impact on critical genes (PIK3CA, AKT1, PTEN, and FMS-like tyrosine kinase 3 [FLT3]), and evaluate therapeutic approaches, including PI3K/AKT inhibitors and miRNA-based interventions. Furthermore, we identified existing controversies, methodological limitations, and unresolved research gaps. Finally, we emphasize the translational potential of miRNA-targeted therapies and pathway-specific inhibitors, providing insights into their integration into personalized treatment strategies for acute leukemia.

Purpose: Tandem autologous stem cell transplantation (tASCT) is a viable option for high-risk multiple myeloma (MM) patients. Minimal residual disease (MRD), a real-time surrogate marker of disease burden, serves as a valuable measure of treatment response. This study evaluated the impact of tASCT on MRD dynamics in MM patients.

Methods: We analyzed data from a multicenter registry of 28 patients who underwent tASCT as frontline treatment between January 2019 and October 2024. Eligibility criteria included undergoing two ASCTs within one year, having MRD positivity before tASCT, and completing follow-up MRD assessment. Patients were stratified into two groups: extensive MRD clearance (≥ 50% reduction, n = 18) and modest MRD clearance (< 50% reduction, n = 10).

Results: Across the entire cohort, mean MRD decreased from 0.111% pre-tASCT to 0.056% post-tASCT. Three patients achieved MRD negativity, 20 had reductions without negativity, and five experienced increases. The extensive clearance group showed significant MRD reduction (0.152% to 0.017%) and longer progression-free survival (PFS: 37.7 vs. 16.3 months, p = 0.013) compared with the modest clearance group, in which MRD increased (0.175% to 0.830%). Overall survival did not differ significantly.

Conclusions: tASCT provides clinical benefit for MRD-positive MM patients, particularly those achieving significant MRD reduction. These findings support tASCT as a feasible approach for MRD-positive patients following initial ASCT.

Purpose: Aggressive natural killer cell leukemia (ANKL) is a rare malignancy with poor prognosis and unclear treatment strategies. Given the poor prognosis and lack of a standardized treatment for ANKL, this study aimed to evaluate the clinical outcomes of L-asparaginase (L-ASNase)-based chemotherapy and hematopoietic stem cell transplantation (HCT).

Methods: This retrospective study analyzed 51 patients with ANKL (2000-2023) to assess the clinical outcomes and efficacy of L-ASNase-based chemotherapy.

Results: Among the study patients, 18 (36.7%) had poor performance status (ECOG-PS ≥ 3) and 7 (13.7%) died before initiating chemotherapy. Of the 44 treated patients, 30 (58.9%) received L-ASNase-based regimens, showing higher response rates (46.7% vs. 21.4%) and a slightly longer median duration of response (4.5 vs 4.2 months) than non-L-ASNase regimens. Complete administration of L-ASNase in the first cycle improved response rates (p = 0.019), but poor performance led to premature discontinuation (p = 0.011). Among the responders, those who subsequently underwent HCT demonstrated prolonged survival compared to those who did not. Median progression-free survival and overall survival were 0.8 and 1.6 months, respectively.

Conclusion: HCT was associated with improved survival, particularly among patients who responded to initial therapy. However, given the high frequency of poor performance status at diagnosis, a stepwise approach, including early supportive care, careful chemotherapy administration, and timely HCT, is crucial for optimizing ANKL outcomes.

The treatment landscape for patients with multiple myeloma (MM) who are ineligible for transplant has evolved significantly over time. Initially dominated by melphalan-based regimens, treatment options have progressed with the introduction of proteasome inhibitors, immunomodulatory drugs, and more recently, anti-CD38 monoclonal antibodies. These advances have led to the development of doublet, triplet, and quadruple regimens, aiming not only for survival benefits, but also for meaningful responses, as represented by minimal residual disease negativity, while maintaining tolerability. The management of frailty in older patients has gained importance, and various frailty assessment tools have been proposed to guide treatment decisions. At the same time, ongoing efforts are being made to develop differentiated treatment strategies for patients with frailty based on frailty status. This review discusses the key therapeutic strategies for patients with MM who are transplant ineligible, the role of frailty assessments, and emerging treatment strategies that promise further evolution in treatment outcomes.

Recent developments in the treatment of lower-risk myelodysplastic syndromes have focused on improving anemia management, which remains a major clinical challenge. Erythropoiesis-stimulating agents (ESAs) and lenalidomide are the standard therapies; however, their effectiveness is limited by resistance and patient selection criteria. Luspatercept, a transforming growth factor-beta superfamily ligand trap, has shown improved transfusion independence and is now considered a frontline option for a broader group of patients. Clinical trials have indicated that luspatercept provides a sustained response in several cases. Imetelstat, a telomerase inhibitor, offers an alternative for patients who do not respond to ESAs and has been shown to reduce the clonal mutation burden, suggesting possible disease-modifying effects. However, unresolved issues remain, such as the lack of predictive biomarkers to guide therapy selection, uncertainty about the optimal sequencing or combination of available treatments, and the fact that most patients eventually progress to higher-risk disease. Additionally, the real-world use of these new agents remains limited in some regions owing to issues with local introduction and reimbursement. This review summarizes recent clinical data on luspatercept and imetelstat, highlights their current limitations, and discusses areas for future research based on recent trial outcomes and evolving clinical practices.

Purpose: Thalassemia is a major public health concern in Southeast Asia, particularly in Malaysia, where a high carrier rate places significant pressure on healthcare systems. Hereditary Persistence of Fetal Hemoglobin (HPFH) and delta-beta (δβ) thalassemia are genetic conditions associated with elevated levels of fetal hemoglobin (Hb F). This study aimed to determine the frequency of common beta (β)-globin gene cluster deletions among Malaysian carriers of HPFH or δβ thalassemia, while also providing an overview of the thalassemia burden in the region.

Methods: A retrospective study was conducted on 534 blood samples submitted to the Institute for Medical Research (IMR), Malaysia, for β-thalassemia genotyping between January 2017 and December 2019. Demographic data, including full blood count parameters and hemoglobin (Hb) analysis, were retrieved. Deoxyribonucleic acid (DNA) was extracted and analyzed using Multiplex Gap-Polymerase Chain Reaction (PCR) to detect large deletions in the β-globin gene cluster.

Results: Seven distinct deletions were identified among the 534 heterozygous carriers. The two most common deletions were ^Gγ(^Aγδβ)°-thalassemia Siriraj I (~ 118 kilobase pairs [kb]) and δβ°-thalassemia Thai (~ 12.5 kb), accounting for 30.0% and 29.8% of cases, respectively. The HPFH-6 deletion was observed in 20.0% of cases, followed by ^Gγ(^Aγδβ)°-thalassemia Asian-Indian Inversion-Deletion (Inv/Del) (14.2%), ^Gγ(^Aγδβ)°-thalassemia Chinese (~ 100 kb) (4.3%), HPFH-3 (0.9%), and ^Gγ(^Aγδβ)°-thalassemia Asian (~ 49.3 kb) (0.7%). The ethnic distribution showed a predominance among Malay patients (93.4%), with specific deletions suggesting ethnic clustering. Genotype-phenotype analysis revealed notable variations in hematological parameters: carriers of HPFH-3 had the highest Hb F levels (25.3 ± 3.1%) as measured by high-performance liquid chromatography (HPLC) and showed the least severe microcytosis, while carriers of δβ°-thalassemia Thai (~ 12.5 kb) demonstrated more pronounced hematological abnormalities. Findings were consistent with previous reports from Southeast Asia, underscoring the importance of incorporating molecular diagnostics into national screening programs. Although Multiplex Gap-PCR is robust, further studies using Next-Generation Sequencing (NGS) and Multiplex Ligation-dependent Probe Amplification (MLPA) are recommended to detect rare or undetected mutations.

Conclusions: This study provides crucial data on the molecular spectrum of HPFH and δβ thalassemia in Malaysia, contributing to improved diagnostic strategies and genetic counselling. Future research should explore additional genetic variants to enhance national thalassemia prevention programs.

Purpose: Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy with varying prognostic outcomes. This study aimed to observe potential patterns or association between RUNX1 mutations and clinical features of AML patients, including hyperleukocytosis, thrombocytosis, and 12-month survival outcomes.

Methods: A prospective cohort study involving 38 patients diagnosed with de novo AML was conducted at the RSUPN Dr. Cipto Mangunkusumo and Dharmais Cancer Hospital between 2022 and 2023. Patients were followed up for 12 months, and RUNX1 mutations within exons 4, 5, 7, and 8 were detected using polymerase chain reaction (PCR)-Sanger sequencing.

Results: This study found RUNX1 mutations in 18.4% of the patients, predominantly in exons 4 and 5. Significant differences in leukocyte counts were observed between patients with and without RUNX1 mutations (p = 0.004). However, no significant association was observed between RUNX1 mutations and hyperleukocytosis or thrombocytosis. Survival analysis revealed that Individuals with RUNX1 mutations had notably lower survival rates (hazard ratio = 6.024, p = 0.014, 95% CI = 1.436-25.279).

Conclusion: In conclusion, RUNX1 mutations may be associated with poor survival outcomes in Indonesian AML patients. Further studies involving larger cohorts and comprehensive molecular analyses are required to confirm the prognostic significance of these findings.

Purpose: Prevention of vascular events is the main objective in patients with polycythemia vera (PV) or essential thrombocythemia (ET). Carotid ultrasonography (USG) is a safe and noninvasive diagnostic tool that can be used to stratify cardiovascular and stroke risks. In our previous study, carotid plaque burden was significantly higher in patients with PV/ET than in the general population. This study aimed to determine changes in carotid plaques in patients with PV/ET.

Methods: We retrospectively evaluated the medical records of patients with ET/PV who had undergone carotid USG at least twice.

Results: Of the 56 patients, 30 had PV and 26 had ET. The carotid plaque score was increased in the follow-up carotid USG compared with that in the initial carotid USG (3.38 ± 1.47 vs. 3.73 ± 1.46, p = 0.0139). The carotid plaque burden at the time of follow-up carotid USG showed no significant differences in patients with a complete hematologic response (CHR); however, it significantly worsened in patients who failed to achieve CHR.

Conclusion: We confirmed that the carotid plaque burden persisted during follow-up in patients with PV/ET. A CHR may prevent an increase in carotid plaque burden.

Background: Peripheral T-cell lymphomas (PTCLs) are a rare and heterogeneous group of aggressive malignancies. This study aimed to comprehensively analyze patients diagnosed with PTCLs in Korea, evaluating treatment outcomes, including transplantation and long-term survival.

Patients and methods: In this retrospective study, clinical data from the National Health Insurance Service on patients with PTCL were investigated. Most patients diagnosed with mature T-cell lymphomas and natural killer (NK)/T-cell lymphomas between January 2005 and December 2022 in Korea were included. Incidence rates of each subtype and survival outcomes of both treated and untreated patients were analyzed.

Results: A total of 12,573 patients were analyzed. PTCL not otherwise specified (PTCL-NOS) and extranodal NK/T-cell lymphoma were the most frequently diagnosed, followed by angioimmunoblastic T-cell lymphoma (AITL). Compared to the general population, the relative survival rate was highest in anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma. With a median follow-up of 6.7 years, the 3-year and 5-year progression-free survival (PFS) rates among treated patients were 44.0% and 39.5%, while the overall survival (OS) rates were 48.6% and 43.5%, respectively. Kaplan-Meier survival curves indicated that patients who added etoposide to the CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) regimen showed improved PFS and OS. In addition, autologous stem cell transplantation significantly improved PFS and OS, particularly in the PTCL-NOS and AITL subtypes.

Conclusion: Patients who received etoposide-containing CHOP-based regimens had improved treatment outcomes. The survival benefits of consolidative autologous stem cell transplantation (auto-SCT) were evident in PTCL-NOS and AITL.