Abstract: Background: Acinetobacter, significantly A.baumannii, are becoming a great threat to hospitalized patients due to increasing antibiotic resistance. The aim of this study was to describe the epidemiology, clinical characteristic, antimicrobial susceptibility pattern and outcome of Acinetobacter infections in pediatric cancer patients and HSCT recipients in Poland. Methods: a total of 125 episodes of Acinetobacter species infections were reported in pa-tients < 18 years treated in Polish pediatric hematology and oncology centers over a pe-riod from 2012 to 2023. Infections were subdivided into oncohematological diseases (OHD) group (n=106; 84,8%) and hematopoietic stem cell transplant (HSCT) group (n=19; 15,2%). Results: A.baumannii is the most common Acinetobacter species in all groups. The most common diagnoses of infected patients in OHD group were: ALL (n=32; 30.2%) and AML (n=13; 12.3%). The most common underlying disease that was indication for HSCT among infected patients were hemophagocytic lymphohistiocytosis (n=3; 15.8%) and neuroblastoma (n=3; 15.8%). In OHD group, deaths did not correlate with the type of antibiotic, with an exception for gentamicin, which correlates with higher mortality. In HSCT group, deaths did not correlate with the type of antibiotic, except for levofloxa-cin that was correlated with higher mortality rate. Mortality was significantly higher in the HSCT group compared to the OHD group. Conclusions: Acinetobacter infections are a great danger to immunocompromised pa-tients. More research is needed in order to prevent and treat antibiotic resistant bacteria.

Abstract: Background: Management of Acute Myeloid Leukemia (AML) and Myelodysplastic Syndromes (MDS) are challenging in low-middle income countries (LMICs) due to lack of advanced diagnostics for risk stratification, restricted finances and lack of trained manpower and infrastructure for handling patients with intensive chemotherapy. Venetoclax when combined with hypomethylating agents (HMA) such as decitabine or azacitidine inhibit electron transport chain complex II resulting in metabolic disruption and eradication of leukemia stem cells (LSCs). Although widely used globally, limited data is available for its use and outcomes from LMICs. Objectives: In this study, we aim to evaluate the outcomes of AML and MDS patients treated with venetoclax and HMA combination therapy in a tertiary care center of Pakistan. Materials and Methods: We conducted a retrospective analysis on 96 patients of which 54 patients had AML and 42 had MDS. All patients received venetoclax combined with HMA at a single center from January 2020 to December 2024. The primary outcomes measured for AML were overall survival (OS), progression free survival (PFS) and response rates (complete remission [CR], partial remission [PR], stable disease [SD] and no response [NR]) while for MDS response was assessed as per International Working Group (IWG criteria). Secondary outcomes were treatment related toxicity (febrile neutropenia, deaths, tumor lysis syndrome) Results: A total of 96 patients were divided into AML cohort (n=54) and MDS cohort (n=42). AML cohort had a male-to-female ratio of 2:1 and a median age of 52 (IQR:37- 62.2). The overall survival (OS), disease free survival (DFS), overall response rate (ORR) and complete remission (CR) was 77.4%, 52.8%, 50% and 88.8% respectively. Of relapsed patients (n=9), only 1 patient responded to salvage therapy. The median OS and DFS for patients receiving salvage HMA was 75% and 12% respectively. Common treatment related toxicities included febrile neutropenia (FN) in 66.7% patients with no treatment related mortality. A total of 12.9% patients underwent consolidative HSCT and 18.5% received off label venetoclax maintenance. The MDS cohort (n=42) had a male-to- female ratio 9.5:1 with 51 years median age. The OS and DFS in MDS cohort were 59.5% and 44.4% respectively. Disease was relapsed in 21.1% patients and median time to response was 64 days. FN occurred in 54.8% patients. Karyotype analysis showed normal cytogenetics in 90.5%. A total of 17.1% MDS patients underwent consolidative HSCT and 12.2% received venetoclax maintenance. Conclusion: HMA-VEN combination therapy is a feasible and effective treatment for patients with MDS and AML presenting in a resource limited setting. However, the low CR rates and high incidence of febrile neutropenia compared to high-income countries underscores the need for better supportive care, comprehensive molecular testing and individualized treatment approaches.

Abstract: T-prolymphocytic leukemia (T-PLL) is a rare lymphoid neoplasm with particularly poor prognosis. B-prolymphocytic leukemia (B-PLL), although no longer recognized as a distinct entity by the World Health Organization (WHO), comprises conditions with unfavorable outcome as well. Both diseases most frequently affect patients in the 7th decade of their lives. Allogeneic hematopoietic stem cell transplantation (alloHSCT) significantly improves outcomes for selected PLL cases as shown by several, mostly retrospective, analyses. In this article, we provide a review of existing PLL analyses, followed by a summary of cases treated at our center. We describe outcomes of six T-PLL and three B-PLL cases receiving alloHSCT at our institution between 2015 and 2022. Despite a post-transplant 4-year cumulative relapse incidence of 61% in our T-PLL series, median OS was 78 months, because relapse therapy was remarkably successful. All B-PLL patients are alive and relapse-free with a median follow-up of 54 (range, 11 – 74) months. A poor pre-transplant Karnofsky performance score (&lt;= 80) and an HCT Comorbidity Index (HCT-CI) of &gt;= 3 were significantly associated with post-transplant mortality. The comparatively favorable outcomes in our case series underline the increasing value of alloHSCT in PLL in the current era, as it offers a prospect of cure in selected patients with otherwise very poor prognosis.

Abstract: Background: Secondary immunodeficiencies in allo-HSCT (allogeneic hematopoietic stem cell transplantation) recipients increase the risk of viral reactivation, making vaccinations a vital issue. There is a paucity of data on the use of recombinant vaccine against herpes zoster (RZV) after allo-HSCT. Methods: The analysis included 149 recipients of allo-HSCT, transplanted in 2012-2022, mainly due to hematological malignancies (>95%). RZV was used from 2021 to 2023 according to the current recommendations of ACIP. The ELISA method was used to assess the VZV IgG antibody titers. Results: VZV reactivation was diagnosed in 49 out of 149(33%) patients before vaccination, including 5(3%) patients with reactivation within the first year after transplantation and the remaining 44(30%) within the subsequent three years. At that time majority of patients were not receiving acyclovir prophylaxis. The most common clinical manifestation of reactivation was involvement of intercostal nerves diagnosed in 40(81%) patients. Twenty-one recipients (median age: 41) received two doses of RZV (at median time-34 months after transplantation, range 12-84 months), the majority of them at an interval of 1 month. The serological post-vaccination response was confirmed in 12 recipients with a ratio of 2.38- 8.3 (median 5.095). The median number of total CD3+CD4+cells in vaccinated patients was 451/μl. Despite vaccination, four patients (19%, three with confirmed serological response) developed herpes zoster. Conclusions: Herpes zoster occurred mainly in the late period after allo-HSCT after completion of acyclovir prophylaxis in over 30% of recipients. The preliminary results indicate that RZV vaccination after allo-HSCT is safe but may have limited effectiveness.

Abstract: Background: Sickle cell disease (SCD) significantly impacts diverse racial groups, particularly African American and Hispanic persons, who experience notable disparities in healthcare outcomes. Despite the extensive literature on SCD, studies focusing on in-hospital racial inequities remain limited. Methods: We conducted a retrospective analysis using the National Inpatient Sample (NIS) from 2016 to 2020, identifying adult hospitalizations for SCD. Hospitalizations were categorized by race—White, African-American, Hispanic, and Other, and analyzed for demographic variables, admission types, disposition outcomes, and complications. Statistical analyses included chi-square tests and multivariate logistic regression, adjusting for confounders. Results: Of the 1,089,270 identified hospitalizations, 90.31% were African-American. African-American and Hispanic patients exhibited significantly higher non-elective admissions compared to Whites (77.81%). In-hospital mortality was highest among Hispanics (0.82%). Multivariate regression analysis revealed that African-Americans and Others had higher odds of prolonged hospital stays (Adjusted Odds Ratio (AOR): 1.30 and 1.20, respectively). African-Americans and Hispanics also had increased risks of in-hospital complications of SCD. Conclusion: This study highlights substantial racial disparities in SCD hospitalizations, with African Americans and Hispanics facing poorer outcomes compared to Whites. Hispanics also demonstrated increased mortality. These findings underscore the need for targeted healthcare interventions to address racial inequities in SCD management and improve outcomes for all affected populations.

Abstract: Fanconi anemia (FA) is an inherited bone marrow failure syndrome characterized by chromosome instability and predisposition to develop myelodysplastic neoplasm (MDS) and acute myeloid leukemia (AML). Clonal chromosome aberrations (CCA) in chro-mosomes 1, 3, and 7 frequently appear in the bone marrow (BM) of patients with FA and associate to MDS/AML progression. Given the underlying DNA repair defect that characterizes FA, non-clonal chromosomal abnormalities (NCCA) are expected to be common events in the FA BM, however little is known about its presence and significance. Here, we transversally examined the BM karyotypes of 43 non-transplanted patients with FA, 41 with non-clinically detectable hematologic neoplasia and two with diagnosed MDS. We searched for the presence of NCCAs, complex karyotypes (CKs) and CCA, and their association with the natural history of the disease, including age, degree of BM failure, and neoplastic transformation. NCCAs were observed in the metaphase spreads of 41/43 FA patients; CKs were observed in 25/43 patients, whereas CCAs were found in 15/43 patients, CCA involving chromosomes 1, 3 and/or 7 in four patients, and other autosomes in the remaining 11 patients. Overall, we observed a baseline large karyotypic heterogeneity in the BM of FA patients, demonstrated by the ubiquitous presence of NCCA; such karyotypic heterogeneity preceding the eventual emergence of CKs and selection of cells carrying fitness-improving CCAs. Finally, CCAs involving chromosomes 1, 3 and 7, well-known drivers of hematological malignancy in FA, become established. Overall, we observed that the frequency of NCCA and CCA increased with age, even though a significant correlation was not found. Preleukemic BM of patients with FA displays a baseline large karyotypic heterogeneity, evidenced by the ubiquitous presence of NCCA; such karyotypic heterogeneity preceding the eventual emergence of CKs and selection of cells carrying fitness-improving CCAs. Finally, CCAs involving chromosomes 1, 3 and 7, well-known drivers of hematological malignancy in FA, become established. These observations fit the model of evolution towards cancer that comprises a first phase of macroevolution represented by NCCA and karyotypic heterogeneity, followed by the establishment of clones with CCA, leading to microevolution and cancer.

Abstract: Background/Objectives: Patients with haematological malignancies use less frequently specialized palliative care, although they may have unmet needs for symptom control, psychosocial and existential burden. The ‘Surprise’-Question “Would you be surprised if this patient died in the next 12 months” helps physicians identifying patients who may benefit from palliative care. We tested influencing factors of the feasibility of the ‘Surprise’-Question in haemato-oncology outpatients. Methods: We performed a prospective cohort study comparing patients with solid tumours and haematological malignancies. All patients in the haemato-oncology outpatient clinics of a German university hospital were screened by haemato-oncologists with the ‘Surprise’-Question. Results: Survival analysis was performed in 672 patients (76% haematological malignancies) at 3 and 12 months. Within one year 110 patients (16%) died. Of these, 30/ 52 (58%) patients with solid tumours, but only 12/ 53 (23%) with haematological malignancies were identified in advance by the ‘Surprise’-Question, which reflects ambiguous test sensitivity. A substantial part of haematology patients in their last year of life were not identified (77%). The match of survival estimates and actual outcome was fair (Cohen’s kappa 0.37). The proximity from prediction to event and the estimating physician rather than patient characteristics influenced the accuracy of the instrument. Conclusions: For the first time the feasibility of the ‘Surprise’-Question in haematology outpatients was proven. Factors improving the haemato-oncologists’ clinical intuition should be further explored to facilitate timely conversation about issues important to patients nearing the end of life.

Abstract: We studied the effects of human blood coagulation on its antioxidant activity, as well as on the cellular secretion of immunoregulatory molecules in vitro. The coagulation process considerably decreased reactive oxygen species (ROS) activity induced by lipopolysaccharide (LPS) in blood samples. Human serum was found to have significantly greater antioxidant activity than plasma. Blood coagulation markedly reduced LPS-induced secretion of (TNF-α) by cells, without significantly affecting the secretion of interleukin-1 (IL-1), IL-6, IL-8 and C-reactive protein (CRP). Blood clotting led to an increase in the spontaneous release of IL-8 and both spontaneous and LPS-induced release of vascular endothelial growth factor (VEGF) by blood cells. A significant increase in procalcitonin levels was also observed in serum samples from blood stimulated with LPS. Thus, blood clotting favors the anti-oxidant and anti-inflammatory functions of immunoreactive blood cells.

Abstract: Introduction: Critically ill COVID-19 patients receiving prophylactic-dose antico-agulation exhibit high rates of thrombosis and mortality. Escalation of anticoagu-lation also does not reduce mortality and has an uncertain impact on the throm-bosis rates. The reasons why escalated doses fail to outperform prophylactic doses in reducing risks of thrombosis and death in critically ill COVID-19 patients remain unclear. We hypothesized that escalated anticoagulation would not ef-fectively prevent plasma hypercoagulability and, consequently, would not reduce the risk of thrombosis and death in some patients. Methods: We conducted a prospective multicenter study that enrolled 3860 COVID-19 patients, including 1654 critically ill. They received different doses of low-molecular-weight or unfractionated heparin, and their plasma coagulability was monitored with activated partial thromboplastin time, D-dimer, and Throm-bodynamics. A primary outcome was plasma hypercoagulability detected by Thrombodynamics. Blood samples were collected at the trough level of antico-agulation. Results: We found that escalated anticoagulation did not prevent hypercoagula-bility in 28.3% of critically ill patients at the trough level of the pharmacological activity. Critically ill patients with hypercoagulability not suppressed by anticoag-ulants had higher levels of inflammation markers and better creatinine clearance compared to critically ill patients without such hypercoagulability. Hypercoagu-lability detected by Thrombodynamics was associated with a 1.75-fold higher hazard rate for death and a 3.19-fold higher hazard rate for thrombosis. Elevated D-dimer levels were also associated with higher hazard rates for thrombosis and death, while shortened APTT were not. Simultaneous use of Thrombodynamics and D-dimer data enhanced the accuracy for predicting thrombotic events and fatal outcomes in critically ill patients. Conclusions: Thrombodynamics reliably detected hypercoagulability in COVID-19 patients and can be used in conjunction with D-dimer to assess the risk of thrombosis and death in critically ill patients. Pharmacological effect of LMWH at the trough level might be too low to prevent thrombosis in some critically ill pa-tients with severe inflammation and better creatinine clearance even if escalated doses are used.

Abstract: Acute myeloid leukemia (AML) corresponds to a heterogeneous group of clonal hematopoietic diseases, which are characterized by uncontrolled proliferation of malignant transformed myeloid precursors and their inability to differentiate into mature blood cells. The prognosis of AML depends on many variables, including the genetic features of the disease. Treatment outcomes, despite the introduction of new targeted therapies, are still unsatisfactory. Recently, there have been an increasing number of reports on enzymatic proteins of the sirtuin family and their potential importance in cancer in general. Sirtuins are a group of 7 (SIRT1-7) NAD+-dependent histone deacetylases with pleiotropic effects on metabolism, aging processes, and cell survival. They are not only responsible for post-translational modification of histones but also play various biochemical functions and interact with other proteins regulating cell survival, such as p53. Thus, their role in key mechanisms of tumorigenesis makes them a worthwhile topic in AML. Different sirtuins have been shown to act oppositely depending on the biological context, the mechanism of which requires further exploration. This review provides a comprehensive description of the significance and role of sirtuins in AML in the light of the current state of knowledge. It focuses in particular on molecular mechanisms regulated by sirtuins and signaling pathways involved in leukemogenesis, as well as clinical aspects and potential therapeutic targets in AML.

Abstract: Despite enormous progress in the development of therapeutic agents for persons with hemophilia A and B (HA, HB), several unmet needs persist. These are disease- and treatment-related. Prophylaxis with clotting factor replacement is the gold standard but not feasible in HA and HB with inhibitors. Whereas persons with HA with inhibitors can receive prophylaxis with a factor-mimicking agent, emicizumab, there is no recommendation on the agents to use as prophylaxis in persons with HB with inhibitors, as there are no available molecules. Concizumab is a novel, subcutaneous prophylaxis option in persons with HA or HB with inhibitors that can potentially improve long-term outcomes. Here, we review the available data on concizumab and discuss its possible positioning in the armamentarium to treat hemophilia with inhibitors.

Abstract: Disease eponyms could be confusing, difficult to remember, scientifically non-robust; lacking implications on and relationship with cell lineage, histogenesis and pathogenesis. This review is geared for revisiting hematolymphoid diseases with eponyms in the light of recent advances in technology and science, by searching the literature using Scopus and Google Scholar with the keywords “eponyms, hematolymphoid, diseases, lymphoma, benign, malignant, lymph node, spleen, liver, bone marrow, leukemia” for the past fifty years. With advances in science and technology, there is accumulation of information on the morphologic nuances, immunologic, immunophenotypic and genetic features of various hematolymphoid eponymic diseases; thus shedding light on important issues of etiology and pathogenesis with implications on therapy in various non-neoplastic (Castleman, Kikuchi-Fujimoto, IgG4-related diseases) and neoplastic (Hodgkin, Burkitt, NK/T-cell lymphomas, dendritic/histiocytic neoplasms and Sezary syndrome) diseases. This contributes to modern nomenclature, classification, subtyping, prognostication and discoveries on new treatment strategies of hematolymphoid eponymic diseases.

Abstract: Acute Myeloid Leukemia (AML) is a complex hematologic malignancy where precise subtype classification is critical for targeted treatment and improved patient outcomes. This study explores the potential of ConvNeXt, an advanced convolutional neural network architecture, for high-resolution peripheral blood smear image classification into AML subtypes. The dataset from a specialized hematopathology center provides a diverse and representative sample, addressing gaps in global leukemia diagnostics. A comprehensive deep learning pipeline was developed, integrating Stochastic Weight Averaging (SWA) for stability, Mixup data augmentation for enhanced generalization, and Grad-CAM for interpretability, ensuring biologically meaningful feature visualization. The ConvNeXt model achieved a state-of-the-art accuracy of 95%, surpassing traditional CNNs (ResNet50, 91%) and transformer-based models (Vision Transformers, 81%), demonstrating its superior feature extraction and classification capabilities. Grad-CAM visualizations provided biologically interpretable heatmaps, enhancing trust in computational predictions and bridging the gap between AI-driven diagnostics and clinical decision-making. Additionally, ablation studies highlighted the contributions of data augmentation, optimizer selection, and hyperparameter tuning, reinforcing the model’s robustness and adaptability. This study advances the role of AI in hematopathology by combining high classification performance, explainability, and scalability, paving the way for equitable and efficient AML diagnostics. Using clinically aligned evaluation metrics (accuracy, F1-score, and ROC-AUC) ensures its practical applicability, establishing a strong foundation for future AI-driven leukemia classification across diverse and underrepresented populations.

Abstract:

Background/Objectives: This study aimed to determine whether interim PET/CT (iP-ET) scans could identify follicular lymphoma (FL) patients at high risk of relapse fol-lowing first-line therapy. Additionally, the potential of cell-free DNA (cfDNA) analysis to complement iPET in predicting outcomes was explored. Methods: A total of 121 FL patients who underwent iPET scans were included, with responses interpreted using the Deauville score (DS). Progression-free survival (PFS) was evaluated over a median follow-up of 34 months. Interim cfDNA data were analyzed for 14 patients to assess its potential for detecting false-positive PET results. Results: Overall, 34% of patients were classified as iPET(+), with significantly worse estimated 5-year PFS compared to iPET(-) patients (29% vs. 72%, hazard ratio 4.31, p < 0.001). Multivariate analysis confirmed iPET(+) as an independent predictor of PFS. Rituximab maintenance was predictive of reduced progression within the iPET(+) group but not among iPET(-) patients. cfDNA analysis identified two false-positive iPET cases and showed potential to identify pa-tients with complete response at risk of early progression. Conclusions: Interim PET results are significant predictors of PFS in FL first-line therapy and could inform re-sponse-adapted treatment strategies. cfDNA analysis has the potential to complement PET/CT by improving specificity and identifying patients at risk of early progression, offering a more precise approach to managing FL.

Abstract: Philadelphia (Ph) negative myeloproliferative neoplasms (MPNs) are disorders caused by abnormal proliferation of myeloid cells in the peripheral blood. Mutations that are responsible for the majority of these cases are those affecting Janus kinase 2 (JAK2), Calreticulin (CalR), and myeloproliferative leukemia virus oncogene (MPL). In this study, we aimed to assess the frequency of CalR and MPL gene mutations and the clinical effects of these mutations in JAK2 gene unmutated MPN patients who were followed up. Despite the lack of statistical significance in 46 patients, it was notable that CalR mutations were more common in patients with esansiyel thrombocytosis (ET), while MPL mutations were only found in patients with primary myelofibrosis (PMF). We found no correlation between thrombosis, leukemic transformation, and driver mutations. The triple negative group had a lower survival rate, but this difference was not statistically significant.

Abstract: CAR-T cell therapy has significantly improved outcomes for patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), but challenges such as limited resources, manufacturing timelines, and notable toxicities persist. Bispecific antibodies (BsAbs), including glofitamab and epcoritamab have demonstrated promising efficacy and represent a new treatment option in patients who are unsuitable for or have relapsed following CAR-T therapy. Bispecific antibodies have a manageable safety profile and are generally more widely accessible than CAR T-cell therapy. Case discussions in this paper illustrate the potential real-world application of BsAbs, highlighting their role in treating patients who have relapsed after or are unable to undergo CAR T-cell therapy. Overall, glofitamab and epcoritamab represent valuable treatment options in the evolving landscape of R/R DLBCL.

Abstract: Multiple myeloma (MM) is a complex and heterogeneous hematologic malignancy characterized by clonal evolution, genetic instability, and interactions with a supportive tumor microenvironment. These factors contribute to treatment resistance, disease progression, and significant variability in clinical outcomes among patients. This review explores the mechanisms underlying MM progression, including the genetic and epigenetic changes that drive clonal evolution, the role of the bone marrow microenvironment in supporting tumor growth and immune evasion, and the impact of genomic instability. We highlight the critical insights gained from single-cell technologies, such as single cell transcriptomics, genomics and multiomics, which have enabled a detailed understanding of MM heterogeneity at the cellular level, facilitating the identification of rare cell populations and mechanisms of drug resistance. Despite the promise of these advanced technologies, challenges remain in their clinical application, including high costs, data complexity, and the need for standardized bioinformatics and ethical considerations. This review emphasizes the importance of continued research and collaboration to address these challenges, ultimately aiming to enhance personalized treatment strategies and improve patient outcomes in MM.

Abstract: Background: Venous thromboembolism (VTE) is a common chronic disease with a considerable risk of recurrence, and early screening for VTE risk assessment and comprehensive data decision-making analyses can reduce its incidence and harm to a certain extent. We proposed a clustering model based on multi-view learning for VTE incidence risk prediction. Methods: This is a retrospective study of 15,856 orthopedic surgical patients who met the diagnosis in a hospital information system between 1992-2017. The risk of developing venous thromboembolism was analyzed and predicted from multiple views using multi-view learning to improve the accuracy of disease prediction. Results: Five multi-view clustering algorithms were selected as comparison algorithms and the performance of these models was evaluated using metrics such as accuracy, purity, and F-score. After comparing the ACC values for each algorithm, it was found that the proposed algorithm had a significantly higher ACC value (0.9172) than the other comparison algorithms (0.6481, 0.6242, 0.7740, 0.8306, and 0.7844, respectively). Conclusions: The proposed algorithm has high effectiveness for VTE risk prediction. The model can assist healthcare professionals to improve the accuracy and timeliness of VTE risk assessment and identify the risk of VTE in patients as early as possible.

Abstract: Every year, more than 150,000 cases of multiple myeloma (MM) are diagnosed worldwide, and over 100,000 deaths caused by this malignancy are recorded. MM incidence is increasing globally, particularly in high-income countries and in the male population aged ≥50. While advances in treatment strategies have led to improvement of survival over the past decades, MM remains incurable in a large percentage of cases. Importantly, about one third of patients diagnosed with MM are >75 years old and are characterized by relatively low fitness or frailty. These patients are more vulnerable to stressors and present a lower resistance to cancer and related treatment. Therefore, patients’ fitness and frailty should become part of standard assessment in MM, and flexible therapeutic options should apply. A careful review of studies investigating the management of frail patients with MM, strongly supports the use of a dynamic assessment of effectiveness and adverse events associated with current treatments in the context of patient-specific frailty and co-morbidities.

Abstract: Acute Myeloid Leukemia (AML) is a heterogeneous hematological malignancy that poses a sig-nificant therapeutic challenge due to its high recurrence rate and demanding treatment regimens. Increasing evidence suggests that endoplasmic reticulum (ER) stress and downstream activation of the unfolded protein response (UPR) pathway plays a key role in the pathogenesis of AML. ER stress is triggered by the accumulation of misfolded or unfolded proteins within the ER. This causes activation of the UPR to restore cellular homeostasis. However, the UPR can shift from promoting survival to inducing apoptosis under prolonged or excessive stress conditions. AML cells can manipulate the UPR pathway to evade apoptosis, promoting tumor progression and re-sistance against various therapeutic strategies. This review provides the current knowledge on ER stress in AML and its prognostic and therapeutic implications.