Relapse and therapeutic resistance remain critical challenges in multiple myeloma (MM). This study investigates the macromolecular drivers of metabolic reprogramming in MM to identify novel therapeutic targets. Through integrated multi-omics profiling, we identified significant dysregulation in long-chain fatty acid metabolism, pinpointing the protein Acyl-CoA Synthetase Long-Chain Family Member 3 (ACSL3) as a central pathogenic factor. Clinical validation revealed that ACSL3 expression is significantly upregulated in MM cell lines and patient bone marrow compared to healthy controls, correlating with disease recurrence. Furthermore, in vitro and in vivo ACSL3 loss- and gain-of-function experiments established ACSL3 as a causal driver of MM cell survival. To elucidate the structural basis for targeting this macromolecule, we performed molecular docking simulations and surface plasmon resonance (SPR) assays. These integrated studies identified gramicidin as a novel direct inhibitor, revealing high-affinity binding interactions within the ACSL3 active site. Functional experimental validation demonstrated that targeting ACSL3 with gramicidin significantly suppressed MM growth in vitro and in vivo, induced apoptosis, and disrupted lipid metabolism. The observed effects were specifically rescued by ACSL3 overexpression. Additionally, we established a robust 8-metabolite signature that accurately predicts MM recurrence, outperforming standard clinical staging. This study characterizes the functional role of the biological macromolecule ACSL3 in MM pathogenesis and provides structural, biological, and preclinical evidence for its inhibition by gramicidin as a potential therapeutic strategy.

The specific prognostic impact of FLT3-ITD variant allele frequency (VAF) in acute myeloid leukemia (AML) remains unclear. In this multi-center study of 190 AML patients harboring FLT3-ITD mutations, a VAF cut-off of 40% was applied. Patients with high VAF (≥ 40%) exhibited significantly higher white blood cell counts, lactate dehydrogenase levels, and bone marrow blast percentages, alongside markedly shorter median overall survival (OS). Although high VAF was independently associated with inferior outcomes in the overall multivariate Cox regression analysis, its effect was profoundly amplified in the presence of co-mutations in NPM1 or DNMT3A. This suggests that high VAF may function not as an absolute, independent determinant, but primarily as a potent "risk amplifier." Notably, allogeneic hematopoietic stem cell transplantation (allo-HSCT) effectively mitigated this survival disadvantage. Furthermore, we characterized a non-linear relationship between VAF and mortality risk, with a sharp increase observed once the VAF burden exceeded 34%. In conclusion, a quantitative VAF ≥ 40% should be considered a context-dependent prognostic marker for risk stratification. Allo-HSCT represents a critical intervention capable of overcoming the exceedingly poor prognosis associated with high VAF.

BACKGROUND:Monoclonal gammopathy of undetermined significance (MGUS) is a precursor to multiple myeloma (MM), but the mechanisms of progression remain unclear. METHODS AND OBJECTIVES:Transcriptomic datasets procured from the Gene Expression Omnibus (GEO) underwent thorough analysis to ascertain disease-related modules using weighted gene co-expression network analysis. A prognostic model (MGUSscore) was constructed via least absolute shrinkage and selection operator (LASSO) regression within the GSE136337 cohort and validated across independent datasets (The Cancer Genome Atlas - multiple myeloma [TCGA-MM], GSE4581, GSE57317). Crucially, the investigation integrated original single-cell ATAC-seq profiling, immune landscape characterization, and pharmacogenomic sensitivity prediction. Protein-level disparities were validated in clinical specimens using immunohistochemistry and multiplex immunofluorescence. RESULTS:DAP3 and UBE2S were identified as central drivers of progression. The MGUSscore effectively stratified patients into risk categories, with high-risk individuals exhibiting significantly inferior survival outcomes (p < 0.001). Notably, the high-risk group was characterized by distinct immune infiltration patterns and predicted responsiveness to specific chemotherapies. Experimental validation confirmed markedly elevated DAP3 and UBE2S protein expression in MM compared to MGUS tissues. CONCLUSION:Collectively, DAP3 and UBE2S may constitute promising therapeutic targets for MM intervention, meriting additional investigative efforts.

Although chimeric antigen receptor T-cell (CAR-T) therapy has reshaped the treatment landscape for relapsed/refractory multiple myeloma (RRMM), durable remission remains challenging. T-cell dysfunction and exhaustion are key obstacles to long-term efficacy. Programmed death-ligand 1 (PD-L1)-positive exosomes may contribute to tumor-associated immunosuppression, but their clinical and functional relevance in multiple myeloma (MM) remains unclear. A total of 89 patients with MM were enrolled, including 34 patients with RRMM treated with CAR-T therapy. PD-L1+ exosome levels in peripheral blood (PB) and bone marrow (BM) were quantified by flow cytometry using exosome-coupled beads, and soluble PD-L1 (sPD-L1) was measured by enzyme-linked immunosorbent assay. Associations with clinicopathological features, treatment response, and progression-free survival (PFS) were analyzed. Effects of RRMM patient sample-derived PD-L1+ exosomes on CD8+ T-cell activation, cytokine production, and exhaustion phenotypes were assessed using in vitro experiments. The therapeutic potential of GW4869 combined with anti-programmed cell death protein 1 (PD-1) antibody to enhance CAR-T efficacy was further evaluated using in vitro and in vivo models. PD-L1+ exosome levels in PB and BM were significantly elevated in newly diagnosed MM and RRMM compared with healthy controls, and were closely associated with adverse prognostic features, including high tumor burden, extramedullary lesions, and high-risk cytogenetic features, whereas plasma sPD-L1 showed no significant clinical correlations. In RRMM patients receiving CAR-T therapy, pretreatment BM and PB PD-L1+ exosome levels discriminated best response (complete response versus less than complete response), with BM showing better predictive performance (area under the receiver operating characteristic curve, 0.846; optimal cutoff, 65.0

Diffuse large B-cell lymphoma (DLBCL), the most common aggressive non-Hodgkin lymphoma, urgently requires novel biomarkers for clinical diagnosis and therapeutic monitoring. Plasma exosomes from three DLBCL patients and three healthy controls were isolated via ultracentrifugation, and differentially expressed circular RNAs (circRNAs) were screened using Arraystar V2 microarrays (fold change [FC] ≥ 1.2, P ≤ 0.05). Candidate circRNAs were validated by quantitative real-time PCR (qRT-PCR) in 55 DLBCL patients and 25 controls. Microarray analysis identified 269 dysregulated circRNAs (152 upregulated, 117 downregulated; FC ≥ 1.2, P ≤ 0.05). RT-qPCR confirmed significantly elevated expression of hsa_circ_400230, hsa_circ_001393, and hsa_circ_404447 in DLBCL (P < 0.05), with areas under the ROC curve (AUCs) of 0.7622, 0.7244, and 0.6618, respectively. High hsa_circ_001393 expression correlated with advanced age (> 60 years), stage III/IV, high International Prognostic Index (IPI 3–5), elevated β2-microglobulin (> 2 mg/L), and non-complete remission (Non-CR) status (P < 0.05). Combined detection with lactate dehydrogenase (LDH) improved predictive efficacy (AUC = 0.817, P = 0.002). Post-chemotherapy complete remission (CR) patients exhibited significant reduction in hsa_circ_001393 (P = 0.0174). Competing endogenous RNA (ceRNA) network analysis identified MLLT3 as a hub gene, with overexpression associated with shorter survival (hazard ratio [HR] = 2.31, P = 0.0042). These findings demonstrate that Plasma exosomal hsa_circ_400230/001393/404,447 are novel diagnostic biomarkers. hsa_circ_001393 predicts therapeutic resistance and dynamically reflects chemotherapy response, potentially via the hsa-miR-1290/MLLT3 axis. This study advances liquid biopsy strategies for DLBCL management.

To investigate the efficacy of Iptacopan in transplantation-associated thrombotic microangiopathy (TA-TMA) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), we report the case of a 43-year-old male with Acute Myeloid Leukemia, Myelodysplasia-Related (AML-MR, with IDH1 and STAG2 mutations) who developed TA-TMA after allo-HSCT. The patient had an initial partial response to the C5 inhibitor eculizumab, but the disease progressed. Oral Iptacopan (200 mg twice daily) was initiated on Day +36. The patient received a total of six sessions of therapeutic plasma exchange and two concurrent doses of defibrotide during the Iptacopan course. After 30 days of Iptacopan treatment, the patient exhibited a significant hematological response, evidenced by a reduction in LDH (758 U/L to 357 U/L), a rise in platelets (17 to 43×109/L), and a drop in C5b-9 (305.32 to 153.70 ng/mL). This biochemical improvement coincided with key clinical outcomes: resolution of proteinuria and the achievement of sustained red blood cell transfusion independence after day +58 and platelet transfusion independence after day +66, marking a decisive turnaround in his TA-TMA course. Treatment with the novel oral complement inhibitor Iptacopan induced significant hematological and clinical responses in this TA-TMA patient, demonstrating its potential therapeutic efficacy and warranting further clinical investigation.

Background:Manganese (Mn), an essential trace element, is involved in various biological processes (BPs). The abnormal metabolism of Mn may be related to the occurrence and development of blood disease. In recent years, studies on manganese metabolism-related genes (MRGs) and acute myeloid leukemia (AML) have gradually attracted attention. The interaction between the immune system and AML is complex. The immune system not only participates in the occurrence and development of leukemia, but also affects the treatment response and prognosis of AML patients. This study aimed to establish a prognostic risk model for AML by combining MRGs and immune-related genes (IRGs). Methods:We constructed a prognostic risk model through univariate and multivariate Cox regression analyses, and validated the predictive efficacy of this model using external datasets. We analyzed the differences in immune infiltration between the high- and low-risk groups. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses were conducted to investigate the roles of five Mn metabolism- and immune-related genes (MIRGs). We also analyzed the immune checkpoint expression levels in AML. The expression levels of the five MIRGs in specific cells were analyzed through single-cell RNA sequencing. All the data analyses were conducted using R software version 4.2.2. Results:This study developed a prognostic risk model based on five MIRGs (CGA, TGFA, GKN1, S100G, and CCL23) linked to cytokine signaling and viral protein interactions. The model, along with age and cytogenetic risk, independently predicted the outcomes of the AML patients. Additionally, the high- and low-risk groups showed distinct immune infiltration patterns and immune checkpoint expression. Conclusions:Our study established an MIRG-based prognostic risk model that can effectively predict the prognosis of AML patients.

An increased risk of secondary primary malignancies (SPMs) has been shown in diffuse large B-cell lymphoma (DLBCL) patients after treatment. However, research on SPM outcomes in DLBCL patients is limited. Utilizing the population-based Surveillance, Epidemiology, and End Results Registry (SEER), the authors examined the characteristics, overall survival (OS), and treatments in DLBCL patients who developed secondary cancers of the breast, prostate, lung, colon/rectum, bladder cancers, melanoma, myeloma, and acute leukemia. Each patient was matched by age, sex, race, year of diagnosis, and stage to 50 controls from a general population diagnosed with a non-DLBCL primary the cancer. Patients with antecedent DLBCL who developed lung cancer (37.3

As phospholipid extracellular vesicles (EVs) secreted by various cells, exosomes contain non-coding RNA (ncRNA), mRNA, DNA fragments, lipids, and proteins, which are essential for intercellular communication. Several types of cells can secrete exosomes that contribute to cancer initiation and progression. Cancer cells and the immune microenvironment interact and restrict each other. Tumor-derived exosomes (TDEs) have become essential players in this balance because they carry information from the original cancer cells and express complexes of MHC class I/II epitopes and costimulatory molecules. In the present study, we aimed to identify potential targets for exosome therapy by examining the specific expression and mechanism of exosomes derived from cancer cells. We introduced TDEs and explored their role in different tumor immune microenvironment (TIME), with a particular emphasis on gastrointestinal cancers, before briefly describing the therapeutic strategies of exosomes in cancer immune-related therapy.

OBJECTIVE:To explore the clinical characteristics and prognostic factors of patients with primary parotid gland lymphoma, and construct a prognostic model nomogram for patients with primary diffuse large B-cell lymphoma (DLBCL) of parotid gland.METHODS:Primary parotid gland lymphoma and primary DLBCL of parotid gland patients from 1984 to 2016 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox regression analysis were conducted to determine the independent prognostic factors of primary parotid gland lymphoma and primary DLBCL of parotid gland, respectively. According to the established independent prognostic factors of primary DLBCL of parotid gland, nomogram was built to predict 3- and 5-year survival, and the discrimination and calibration of the model were evaluated by concordance index (C-index) and calibration plots.RESULTS:A total of 2 610 patients with primary parotid gland lymphoma were identified. Their median age was 66(15-99) years old, the male to female ratio was 1∶1.8, and 20.5% of them was primary DLBCL of parotid gland, which was the most common histological subtype in aggressive lymphomas. Multivariate Cox regression analysis showed that sex, age, Ann Arbor stage, years of diagnosis, marital status, histological subtype, surgery, and radiation were the independent prognostic factors of primary parotid gland lymphoma, while age, marital status, surgery, and chemotherapy were the independent prognostic factors of primary DLBCL of parotid gland. The C-index of the prediction model was 0.702(95%CI: 0.696-0.768), reflecting a good discrimination ability. The predicted value probability of the calibration plots was close to the actual value probability, reflecting a good accuracy ability.CONCLUSIONS:Sex, age, Ann Arbor stage, years of diagnosis, marital status, histological subtype, surgery, and radiation were the independent prognostic factors of primary parotid gland lymphoma. The nomogram survival prediction model for primary DLBCL of parotid gland patients can assist clinical decision effectively.

PD-L1+ exosome have been reported to be a promising prognostic biomarker in various cancers. However, its clinical value in diffuse large B cell lymphoma (DLBCL) has not been defined yet. In this study, a total of 165 plasma samples from 78 patients with DLBCL undergoing standard first-line R-CHOP regimens were collected at three different time points (pretreatment, and after 3 and 6 cycles of R-CHOP) to determine the proportions of PD-L1+ exosomes by flow cytometry. We found that high pretreatment plasma PD-L1+ exosome correlated with indicators of poor clinical outcome that included high Ki-67 expression (P = 0.02), double expressor lymphoma (P = 0.005), immunohistochemical PD-L1+ tumor tissue (P = 0.006), and the baseline maximal standardized uptake values (P = 0.0003). Pretreatment plasma PD-L1+ exosome was an independent factor by multivariate analysis with logistic regression (P = 0.0301). Moreover, the pretreatment PD-L1+ exosome was a strong predictor of final treatment responses of either CR or non-CR by ROC analysis (P < 0.001). PD-L1+ exosome level declined significantly in patients who experienced CR (pretreatment vs. after 3 cycles/after 6 cycles, P < 0.05), but not in the non-CR group. Intriguingly, plasma PD-L1+ exosome after 3 cycles (AUC = 0.857; 95

Acute graft-versus-host disease (aGVHD) is a severe complication of allogeneic hematopoietic stem cell transplantation. Hematopoietic dysfunction accompanied by severe aGVHD, which may be caused by niche impairment, is a long-standing clinical problem. However, how the bone marrow (BM) niche is damaged in aGVHD hosts is poorly defined. To comprehensively address this question, we used a haplo-MHC-matched transplantation aGVHD murine model and performed single-cell RNA-Seq of nonhematopoietic BM cells. Transcriptional analysis showed that BM mesenchymal stromal cells (BMSCs) were severely affected, with a reduction in cell ratio, abnormal metabolism, compromised differentiation potential, and defective hematopoiesis-supportive function, all of which were validated by functional assays. We found that ruxolitinib, a selective JAK1/2 inhibitor, ameliorated aGVHD-related hematopoietic dysfunction through a direct effect on recipient BMSCs, resulting in improved proliferation ability, adipogenesis/osteogenesis potential, mitochondria metabolism capacity, and crosstalk with donor-derived hematopoietic stem/progenitor cells. By inhibiting the JAK2/STAT1 pathway, ruxolitinib maintained long-term improvement of aGVHD BMSC function. Additionally, ruxolitinib pretreatment in vitro primed BMSCs to better support donor-derived hematopoiesis in vivo. These observations in the murine model were validated in patient samples. Overall, our findings suggest that ruxolitinib can directly restore BMSC function via the JAK2/STAT1 pathway and, in turn, improve the hematopoietic dysfunction caused by aGVHD.

OBJECTIVE:To investigate the effects of decitabine (DEC) combined with all-trans retinoic acid (ATRA) on the number of immune cells, efficacy and adverse reactions in the treatment of myeloid neoplasms patients. METHODS:Eighty-four patients with myeloid tumors, including AML, MDS-EB-1 or MDS-EB-2 treated by the regimen containing decitabine in our hospital from January 2009 to October 2019 were enrolled and retrospectively analyzed, among the patients, 21 patients treated with DEC alone, 24 patients treated with DEC combined with ATRA (DEC/ATRA) and 39 patients treated with DEC combined with G-CSF priming regimen (DEC/priming). The changes of peripheral blood immune cell levels before and after treatment of the patients between the three groups were compared, and the differences in clinical efficacy and adverse reactions of the patients between the three groups were also compared. RESULTS:There was no statistical differences in the number of immune cells among the patients in the three groups before treatment (P>0.05). NK cell levels decreased significantly in the patients in DEC and DEC/ATRA group after treatment (P<0.05); After treatment, the levels of CD8+ and CD3+T cells in the patients treated by DEC /priming regimen significantly increased (P<0.05), while the levels of CD3-HLA-DR+ B cells significantly decreased (P<0.05). The overall response rate (ORR) of the patients in DEC/ATRA group (75%) and DEC/priming group (74.36%) was significantly higher than 42.86% in DEC monotherapy group, and the differences showed statistically significant (P<0.05), while the ORR between the patients in DEC/ATRA and DEC/priming group showed no statistic differences (P>0.05). There were no statistical differences in overall survival (OS) and incidence of bleeding between the patients in the three groups (P>0.05). The incidences of grade 3 to 4 bone marrow suppression and the infection rate of the patients in DEC monotherapy and DEC/ATRA group were significantly lower than that in DEC/priming regimen group after treatment (all P<0.05), however, there was no statistical difference between DEC monotherapy and the DEC/ATRA group. CONCLUSION:The efficacy of DEC/ATRA on myeloid neoplasms is comparable to that of DEC/priming regimen, and the anti-myeloid tumor effect of DEC/ATRA regimen may be related to the regulation of NK cells and T cells.

OBJECTIVE:To investigate the clinical value of neutrophil CD64 index in hematological malignancies with pulmonary infection.METHODS:The cohort study method was used to retrospectively analyze the clinical data of 125 patients with hematological malignancies and pulmonary infections who were treated in The Third Affiliated Hospital of Soochow University. All the patients were divided into four stages according to the diagnosis and treatment process: non-infected stage (T1), the symptoms of infection had appeared before using antibiotics (T2), one week after anti-infective treatment (T3), and after stopping antibiotics (T4). CD64 index, C-reactive protein (CRP), blood cell count, and immune cell level were compared before and after infection (T1 vs T2), the correlation between CD64 index and other indicators were explored, the change trends of the significantly different indicators in the course of the disease were observed, and the diagnostic efficacy of CD64 index and CRP were compared. The surviving patients were followed up for whether reinfection occurred within 30 days after discharge, and the re-examination results of indices before discharge (in stage of T4) between reinfected and non-reinfected patients were compared to find the risk factors of reinfection.RESULTS:Before and after infection, the CD64 index, CRP, CD14+HLA-DR+, CD4+, and lymphocyte counts were significantly different (all P<0.05). There was a negative correlation of CD64 index with CD14+HLA-DR+ (r=-0.395, P<0.001), a negative correlation with CD3+ (r=-0.1.87, P=0.047), and a negative correlation with lymphocyte count (r=-0.230, P=0.006), while a positive correlation with CRP(r=0.313, P<0.001). The area under the curve of CD64 index, CRP, and CD64 index combined with CRP was 0.790 (95%CI: 0.711-0.868), 0.754(95%CI: 0.667-0.841), and 0.835(95%CI: 0.762-0.907), respectively; the sensitivity was 59.6%, 72.7%, and 74.7%, the specificity was 89.2%, 73.0%, and 78.4%, and the cut-off value was 0.488, 0.457, and 0.531, respectively. There were only two re-examination indexes showed significantly different before discharge between reinfected patients and non-reinfected patients: CD14+HLA-DR+ (F=8.524, P=0.004) and CD64 index (F=9.993, P=0.002). The increase of CD64 index was an independent risk factor for reinfection within 30 days after discharge from the hospital (HR=1.790, 95%CI: 1.343-2.386, P<0.001).CONCLUSION:CD64 index has diagnostic value in patients with hematological malignancies and pulmonary infection, and its specificity is higher than that of CRP. The combination of the two indicators can improve the diagnostic sensitivity. CD64 index has a predictive value for reinfection within 30 days after infection treatment.

OBJECTIVE:To investigate the efficacy and safety of bendamustine combined with gemcitabine, vinorelbine，glucocorticoids (BeGEV)±X regimen in treatment of patients with relapsed/refractory non-Hodgkin lymphoma.METHODS:A total of 18 relapsed/ refractory non-Hodgkin lymphoma patients at the age of 18 years or older hospitalized in the First People's Hospital of Changzhou from March 2020 to March 2021 were selected. They received two or more cycles of BeGEV±X regimen. X could be anti-CD20 monoclonal antibody, PD-1-blocking antibodies, lenalidomide, BTK inhibitor, Bcl-2 inhibitor and so on according to patients' disease feature. The clinical efficacy and adverse effects were observed.RESULTS:In total, 18 patients completed two or more cycles of BeGEV±X regimen, including 14 with diffuse large B-cell lymphoma, one with low-grade follicular lymphoma, one with follicular lymphoma grade 3b, one with angioimmunoblastic T-cell lymphoma and one with peripheral T-cell lymphoma, not otherwise specified. 11 patients were male. The median age of the patients was 64 years old. 17 patients had modified Ann Arbor stage Ⅲ/Ⅳ disease. 13 patients had high- intermediate risk or high risk IPI score, while 15 patients had high-intermediate high risk or high risk NCCN-IPI score. 14 cases had extranodal sites of disease. And 6 cases had bulky disease. 12 patients experienced refractory disease, while 8 patients had received 3 line or more prior treatment. After two or three cycles of chemotherapy, the complete response rate was 6/18, the partial response rate was 3/18, and the objective response rate was 9/18. From the beginning of salvage chemotherapy to the end of follow-up, the median progression-free survival time was 130 days, and the median overall survival was 152 days. The most common grade 3 to 4 adverse events were hematologic toxicities, infection and febrile neutropenia.CONCLUSION:BeGEV±X is an effective salvage regimen in treatment of patients with relapsed/refractory non-Hodgkin lymphoma, while adverse events such as hematologic toxicities and infection should be closely monitored.

BACKGROUND Although the V617F mutation in the Janus kinase 2 (JAK2) gene and the breakpoint cluster region-abl1 (BCR-ABL1) oncogene fusion have been considered mutually exclusive in most myeloproliferative neoplasms (MPNs), many recent studies have described patients with both. This report describes a patient with chronic myelogenous leukemia (CML) and the unusual JAK2 R795S mutation and reviews 23 additional patients with JAK2 gene mutations coexisting with myelofibrosis (MF) and CML. CASE REPORT A 50-year-old woman with MF experienced rapid disease progression 3 weeks later, accompanied by severe abdominal pain and a white blood cell count of 257.45×10⁹/l. Karyotype analysis indicated that she was 46, XY, Philadelphia (Ph) (+) and BCR-ABL1 positive. Bone marrow aspiration after 1 cycle of chemotherapy and treatment with dasatinib showed that her marrow was hypercellular, with an increased number of megakaryocytes and 48.5% myeloblasts expressing the myeloid antigens CD33, CD13, CD34, CD117, and CD71. Next-generation sequencing identified a rare JAK2 R795S mutation. She was diagnosed with CML in blast phase, and was successfully treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT). CONCLUSIONS JAK2 gene mutations, including the rare JAK2 R795S mutation, can coexist with BCR-ABL1 in patients with MPNs. The clinical course of MPN in patients with both BCR-ABL1 and JAK2 mutations may be different from that in patients with classical MPNs.

This study aimed to investigate the efficacy and mechanism of decitabine (DAC) and all-trans retinoic acid (ATRA) in elderly acute myeloid leukemia (AML) patients and cultured cells. Our clinical trial enrolled 36 elderly patients who were judged ineligible for conventional chemotherapy, receiving DAC and ATRA regimen (DAC 20 mg/m(2) days 1-5; ATRA 20 mg/m(2) days 4-28 in the first cycle and days 1-28 in the subsequent cycle). Treated with a median of 3 cycles (range 1-6), 44.4 % of patients achieved complete remission (CR), 11.1 % achieved CR with incomplete peripheral count recovery (CRi) and 13.9 % achieved partial remission (PR). The median overall survival (OS) was 12.1 months; the 1-year and 2-year OS rates were 49.6 % and 17.2 %. In addition, our in vitro studies indicated that the antineoplastic activities of DAC and ATRA mutually reinforced, which induced growth inhibition, cell cycle arrest and apoptosis of AML cells. Meanwhile, we found DAC and ATRA inhibited DNMT1, activated miR-34a via promoter hypomethylation, down-regulated its target MYCN and thus exerted a synergistic antineoplastic effect. In conclusion, DAC plus ATRA regimen might be effective and well-tolerated for elderly patients partially through modulating miR-34a/MYCN axis.