Venetoclax-based regimens have become increasingly integrated into the therapeutic landscape of acute myeloid leukemia (AML), yet primary resistance and relapses remain major barriers to durable benefits. Building on our previous discovery of CD84 as a critical survivor and redox regulator in AML, we here demonstrate that CD84 expression contributes to venetoclax sensitivity. Low CD84 expression is associated with favorable clinical response, whereas high CD84 expression correlates with primary resistance and is up-regulated at relapse in two of three paired samples. Functional perturbation of CD84 through genetic knockdown or CD84-targeted CAR-T cells sensitized AML cells to venetoclax in vitro and in vivo cell-derived xenograft models. Mechanistically, CD84 coordinates a pro-survival program with upregulating the antioxidant stress sensor SESN2, which suppresses mitochondrial reactive oxygen species and antagonizes venetoclax-induced apoptosis. SESN2 knockdown phenocopied CD84 depletion, while SESN2 overexpression partially restored venetoclax resistance in CD84-deficient cells. Our findings suggest that CD84-mediated upregulation of SESN2 contributes to venetoclax resistance and may represent a potential therapeutic target to enhance treatment efficacy in AML.

To evaluate the real-world application of ivosidenib (IVO) in patients with IDH1-mutated acute myeloid leukemia (AML), as well as its efficacy and safety. We retrospectively analyzed clinical data from 16 patients with IDH1-mutated AML who received IVO-based therapy at Nanfang Hospital between September 2021 and May 2025. The median age was 57 years (range, 25 - 80 years), with 7 males and 9 females. Six patients (37.5%) had an Eastern Cooperative Oncology Group performance status of 3 - 4, and 14 patients (87.5%) were classified as intermediate- or high-risk according to the European LeukemiaNet criteria. Among 5 patients (31.2%) receiving venetoclax (VEN) plus azacitidine (AZA) combined with IVO for induction, 3 achieved complete remission (CR), including 2 with measurable residual disease (MRD) -negative and IDH1 dPCR-negative status. Two patients (12.5%) received VA plus IVO for consolidation; both maintained CR, with 1 achieving MRD-negative and IDH1 dPCR-negative status. Four relapsed or refractory patients (25.0%) received VEN plus hypomethylating agents (HMA) combined with IVO (n=3) or IVO alone (n=1) for salvage therapy. All patients achieved CR, of whom 3 obtained MRD-negative results, and 1 was IDH1 dPCR-negative. Five patients (31.2%) received IVO as maintenance therapy, with a duration of response exceeding 12 months. The most common grade ≥3 adverse events were neutropenia (56.3%), anemia (43.8%), and thrombocytopenia (37.5%). IVO-related adverse events included differentiation syndrome (12.5%) and QT interval prolongation (12.5%), and no treatment-related deaths were observed. IVO-based regimens demonstrated favorable efficacy and a manageable safety profile across all treatment phases in patients with IDH1-mutated AML, supporting their broader clinical application.

This study aimed to investigate the clinical characteristics of primary pure erythroid leukemia (PEL) in children, particularly PEL with NFIA::CBFA2T3 or NFIA::RUNX1T1 fusions. We retrospectively analyzed clinical data from three children with PEL who were treated at the Capital Center for Children's Health, Capital Medical University, between September 2017 and September 2021, and reviewed the literature. All three patients had cytogenetic alterations: case 1 had t (1;16) (p32;q24), case 2 had an NFIA::CBFA2T3 fusion, and case 3 had an NFIA::RUNX1T1 fusion. All three patients responded poorly to standard intensive chemotherapy for acute myeloid leukemia (AML) and to regimens containing hypomethylating agents. Cases 1 and 3 died after continued disease progression. Case 2 underwent intensive chemotherapy followed by umbilical cord blood stem cell transplantation, relapsed 2 months after transplantation, and died soon thereafter. These findings suggest that primary PEL in children is characterized by an insidious onset, rapid progression, and poor response to commonly used AML chemotherapy regimens, and that patients may benefit from hematopoietic stem cell transplantation after achieving complete remission.

This study retrospectively analyzed 407 newly diagnosed patients with non-M(3) acute myeloid leukemia (AML) treated at the First Affiliated Hospital of Soochow University between 2016 and 2024. Based on the ISTH-2018 DIC score, patients were classified into a DIC group (n=109) and a non-DIC group (n=298), and their clinical characteristics and survival were compared. The results showed that white blood cell count, bone marrow blast percentage, alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase levels were significantly higher in the DIC group than in the non-DIC group (all P<0.001). Molecular analysis indicated that NPM1, FLT3-ITD, and SETD2 mutations were significantly enriched in the DIC group (all P<0.05). Multivariable logistic regression showed that a high white blood cell count, a high blast percentage, an elevated lactate dehydrogenase level, and NPM1 mutation were independent risk factors for DIC (all P<0.05). Clinical outcome analysis showed that the DIC group had a higher incidence of early severe bleeding (P<0.001) and a lower complete remission rate after first induction chemotherapy (P<0.05). In the overall population, especially in the European LeukemiaNet (ELN) 2022 high-risk subgroup, overall survival (OS) was significantly worse in the DIC group than in the non-DIC group (P<0.05). Multivariable Cox regression further confirmed that concomitant DIC, early severe bleeding, and older age were independent risk factors for OS in patients with non-M(3) AML (all P<0.05). These findings suggest that DIC in non-M(3) AML is closely associated with a high tumor burden and specific molecular abnormalities and is accompanied by a higher risk of early bleeding and poorer survival outcomes. DIC may therefore represent a higher-risk clinical feature requiring enhanced early monitoring and risk-stratified management.

Objective: To compare the clinical characteristics and prognosis of patients with acute myeloid leukemia (AML) harboring single-site versus multi-site mutations in the RUNX1 gene. Methods: This study was a retrospective cohort study. 145 patients with RUNX1-mutated AML treated at the First Affiliated Hospital of Soochow University between June 2017 and June 2023 were selected. Single-site RUNX1 mutations were observed in 123 patients, whereas multi-site mutations were detected in 22 patients. The outcomes of interest included overall survival (OS), recurrence-free survival (RFS), and the first-course induction remission rate, defined as the sum of complete remission and complete remission with incomplete hematologic recovery. Results: A total of 145 patients with RUNX1-mutated AML were included, including 87 males and 58 females, with a median age of 49 years (range, 17-78 years). The two groups showed no significant differences in age, sex composition, peripheral blood counts at diagnosis, karyotype, fusion genes, or risk stratification (all P>0.05). The median number of co-occurring gene mutations was 3 (range, 0-11) in the single-site group and 5 (range, 2-10) in the multi-site group, indicating a significantly higher number in the latter (P=0.001). However, the distribution of co-occurring mutations did not differ significantly between groups (P>0.05). There were no significant between-group differences in the first-course induction remission rate (53.3% vs 50.0%, P=0.819), median OS (45.67 vs 36.53 months, P=0.942), or median RFS (17.13 vs 21.17 months, P=0.679). In the single-site mutation group, patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) achieved 3-year OS and RFS rates of 74.7% and 58.5%, respectively, significantly higher than the 31.2% and 27.9% among those without transplantation (both P<0.001). In the multi-site mutation group, the 3-year OS and RFS rates were 69.2% and 69.2%, respectively, among allo-HSCT recipients, significantly higher than 33.3% and 0, respectively, among nonrecipients (P=0.003 and P=0.001, respectively). Multivariate Cox proportional hazards analysis identified allo-HSCT as an independent protective factor for OS (single-site group: HR=0.256, P<0.001; multi-site group: HR=0.164, P=0.043) and RFS (single-site group: HR=0.528, P=0.025; multi-site group: HR=0.142, P=0.030) . Conclusion: Patients with AML harboring single-site and multi-site RUNX1 mutations did not differ significantly in clinical characteristics, treatment response, or long-term prognosis. Allo-HSCT was associated with improved survival outcomes in both groups.

Objective: To investigate the long-term survival outcomes of salvage allogeneic hematopoietic stem cell transplantation (R/R AML) . Methods: This was a retrospective real-world study. We conducted a retrospective analysis of 510 patients with R/R AML who underwent allo-HSCT at Aerospace Center Hospital between July 2012 and December 2024. All patients had active disease before transplantation, defined as a bone marrow blast proportion of at least 5%. Overall survival (OS) and disease-free survival (DFS) were assessed using the Kaplan-Meier method, whereas the cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) were evaluated by competing-risk models. Univariate analysis was performed using the log-rank test, and multivariable analysis was conducted using Cox regression for survival outcomes and Fine-Gray regression for competing-risk outcomes to identify independent prognostic factors. Results: In this cohort of 510 patients, the median follow-up duration was 50 months (range, 0-151 months). The estimated 10-year overall survival (OS) and disease-free survival (DFS) rates were 35.5% (95% CI: 31.2% -40.5% ) and 33.2% (95% CI: 29.1% -38.0% ), respectively. Multivariable analysis demonstrated that European LeukemiaNet (ELN) risk stratification was a core prognostic factor. Patients in the intermediate-risk (HR=1.74, P=0.002) and adverse-risk (HR=1.97, P<0.001) categories had markedly lower OS and DFS rates. Mild-to-moderate chronic graft-versus-host disease (cGVHD) served as a protective factor for OS and DFS (both P<0.001). A diagnosis-to-transplant interval longer than 10 months (HR=1.56, P<0.001) was correlated with poor survival outcomes. A higher infused CD34(+) cell dose (≥4.3×10(6)/kg) was independently associated with superior OS (HR=0.64, P<0.001) and DFS (HR=0.62, P<0.001). In competing-risk analysis, intermediate and adverse ELN risk stratification (HR=2.73 and 2.90, respectively; both P<0.001) and elevated bone marrow blast percentage (≥50% ) (HR=1.62, P=0.037) were independently linked to increased relapse risk. Mild, moderate, and severe cGVHD, compared with no cGVHD (HR=0.38, 0.13, and 0.24; P<0.001, P<0.001, and P=0.015, respectively), and grade Ⅲ-Ⅳ acute graft-versus-host disease (aGVHD) (HR=0.54, P=0.033) were associated with a lower CIR. Regarding non-relapse mortality (NRM), grade Ⅲ-Ⅳ aGVHD (HR=2.36, P<0.001) and severe cGVHD (HR=2.74, P<0.001) were major risk factors, and advanced age (HR=1.47, P=0.033) was also associated with higher NRM. Conclusions: This study indicates that long-term disease-free survival may be attained through salvage allo-HSCT in patients with R/R AML despite active disease at transplantation. Long-term outcomes are mainly determined by disease biology and post-transplant immune effects, with ELN risk stratification and GVHD playing dominant roles, whereas pre-transplant tumor burden mainly affects relapse risk but is not an independent determinant of long-term survival. These findings suggest that greater emphasis should be placed on risk stratification and transplantation timing in clinical practice, rather than solely pursuing complete remission prior to transplantation.

Acute myeloid leukemia (AML) with KMT2A gene rearrangements has been observed to demonstrate an aggressive biological behavior, especially in pediatric cases. Cytogenetic abnormalities that are extremely uncommon, such as t(1;11)(q21;q23), in addition to other chromosomal abnormalities, can further impact the clinical course of the disease. The aim of the study is to report on an uncommon case of pediatric AML with a t(1;11)(q42;q23) involving a KMT2A gene rearrangement together with other chromosomal abnormalities, emphasizing the importance of performing cytogenetics and FISH studies for hematopoietic workups and an accurate diagnosis. Cytogenetic evaluation was done using conventional karyotype analysis. FISH studies using the KMT2A break-apart probe were used to establish the existence of gene rearrangement. To determine the partner chromosome, whole chromosome FISH painting was performed. Immunophenotypic studies were also performed to determine antigen expression. A two-year-old child diagnosed with AML had multiple chromosomal abnormalities, including t(1;11)(q42;q23), trisomy 8, trisomy 21, and 47,XYYc karyotype. There were four fusion signals for KMT2A obtained from FISH studies with two presenton chromosome 1. Whole chromosome painting provided confirmation for these results. Abnormal expression of CD7 antigen was demonstrated through immunophenotypic evaluation and indicated a poor prognosis. This case study shows that AML with a KMT2A gene rearrangement is associated with an aggressive clinical course and uncommon cytogenetics. It emphasizes the need to use FISH and cytogenetics together for the detection of gene fusions, partner chromosomes, and other cytogenetic aberrations.

The KAT6A::NCOA2 (formerly MOZ::TIF2) fusion is an extremely rare recurrent genetic abnormality in acute myeloid leukemia (AML), with only nine cases reported to date. It has consistently been associated with inv(8)(p11q13). However, the genomic mechanism underlying this fusion has remained unresolved. Because both KAT6A and NCOA2 are transcribed in the same reverse orientation on chromosome 8, a simple inversion is structurally insufficient to generate a transcriptionally competent fusion transcript, creating a long-standing cytogenetic paradox. We analyzed an AML case harboring a KAT6A::NCOA2 fusion using targeted genomic profiling and breakpoint-level validation. In addition to the canonical KAT6A::NCOA2 fusion, sequencing identified an unexpected MTFR1::KAT6A rearrangement. Since MTFR1 is located between KAT6A and NCOA2 on chromosome 8, we hypothesized a complex intrachromosomal rearrangement. Genomic breakpoint analysis revealed that the fusion was generated not by a single inv(8), but by two adjacent intrachromosomal inversions forming a tandem double inversion. This rearrangement reoriented genomic segments to place KAT6A and NCOA2 in a transcriptionally compatible configuration, enabling fusion formation. These findings resolve the structural paradox of KAT6A::NCOA2-positive AML by demonstrating that a cytogenetically apparent inv(8)(p11q13) can conceal a tandem double-inversion architecture that reorients KAT6A and NCOA2 into a transcriptionally compatible configuration.

Gastrointestinal intolerance and limited intestinal residence remain important challenges in the long-term oral use of metformin (MET) for type 2 diabetes mellitus (T2DM). Although liposomal encapsulation can improve drug delivery, unmodified MET-encapsulated liposomes remain vulnerable to gastrointestinal disruption and premature leakage, which undermines their therapeutic potential. To address this limitation, Agaricus bisporus-derived chitosan (ACS) was employed as a bioactive macromolecular coating to construct MET-encapsulated liposomes (MET-LP). The ACS coating reversed the surface charge of MET-LP, improved colloidal dispersion, and enhanced storage stability, with 0.5% ACS-modified MET-encapsulated liposomes (A-M-L) retaining 83.1% encapsulation efficiency after 21 days at 4 °C. In T2DM mice, 1.0% A-M-L produced stronger glycemic control, lowering fasting blood glucose from 14.3 to 8.6 mmol/L, reducing HbA1c by approximately 32.9%, and decreasing the area under the curve (AUC) of the oral glucose tolerance test (OGTT) by 37.7%. Moreover, A-M-L improved serum lipid profiles and hepatic oxidative-stress-related indicators and was associated with lower ileal inflammatory cytokine levels and better-maintained gastrointestinal tissue morphology in T2DM mice. ACS modification also enhanced the intestinal retention of labelled liposomal carriers, as indicated by a 233.3% higher ileal fluorescence intensity of 0.5% A-M-L than unmodified MET-LP in SD rats. Collectively, these findings indicate that ACS modification improved the formulation stability, intestinal retention of labelled liposomal carriers, and hypoglycemic performance of MET-encapsulated liposomes.

Since the discovery of cytotoxic agents in the mid-20th century, acute leukemia has consistently served as a model for oncology research. As the Human Genome Project and subsequent genomic profiling elucidated the landscape of somatic mutations and cytogenetic aberrations driving leukemogenesis, the development of molecularly targeted therapies has dramatically accelerated, yielding significant improvements in patient outcomes. In acute myeloid leukemia (AML), the emergence of selective inhibitors targeting high-frequency alterations such as FLT3, NPM1, and IDH1/2 has redefined the standard of care, demonstrating superior efficacy when combined with conventional intensive chemotherapy or hypomethylating agents. Simultaneously, for acute lymphoblastic leukemia (ALL), in addition to the significant improvements achieved by tyrosine kinase inhibitors (TKIs) for BCR-ABL-positive ALL, the advent of CD19- or CD22-targeted monoclonal antibodies and CAR-T cell therapies has marked an epoch-making milestone, representing a major paradigm shift in the management of relapsed or refractory cases. Bridging these two distinct lineages, menin inhibitors have emerged as a novel class of agents targeting a common pathogenic mechanism in KMT2A-rearranged AML/ALL and NPM1-mutated AML, exhibiting promising antileukemic activity across these subtypes. In this review, we describe the evolution of leukemia therapy-highlighting historical trajectory across AML, APL, and ALL from uniform cytotoxic chemotherapy to molecularly targeted agents, antibody-based therapies, and chemo-free paradigms, while outlining future perspectives for precision hematology.

Changes in cell-cell communication during disease can result from shifts in tissue composition, variations in the proportion of cells engaged in signaling, and differences in ligand-receptor expression. To address this, we developed community, an R package designed for differential communication analysis in multi-sample case-control scRNAseq datasets. Community reconstructs interactions by evaluating cell type abundance, the active fraction of cells, and their expression levels. This method identifies communication patterns that are upregulated, downregulated, unchanged, or compensated. Applied to ulcerative colitis, melanoma under immune checkpoint inhibitor treatment, and acute myeloid leukemia, community captured disease- and response-associated communication changes, including increased communication in ulcerative colitis, reduced immunosuppressive signaling in melanoma responders, and decreased immune communication in AML. Comparisons with existing tools showed improved robustness to outlier-driven signals and better scalability. These component-level analyses help connect altered communication patterns to biological mechanisms in healthy and disease states.

Nucleophosmin-1 (NPM1) mutations define a major molecular subtype of acute myeloid leukemia (AML) and is generally associated with favorable prognosis. However, the impact of myelodysplastic syndrome-associated mutations (MDS[m+]) on patient outcomes within this subgroup remains uncertain. We retrospectively analyzed 271 patients with NPM1-mutated AML from 3 independent cohorts (SWOG, Fred Hutch, and Beat AML) to assess the prognostic significance of MDS[m+] and its interaction with age. MDS[m+] occurred in 17% of patients, most commonly involving SRSF2 and SF3B1. Although MDS[m+] was associated with inferior overall survival (OS) compared with MDS[m-] in European LeukemiaNet (ELN) 2022 favorable-risk patients (hazard ratio [HR], 2.0; P = .008), this effect was largely driven by worse outcomes in older patients (≥65 years) as older ELN2022 favorable-risk patients had poor OS regardless of the presence of MDS[m+] compared with younger patients. After stratification of patients by age, there was not a significant difference between MDS[m+] and MDS[m-] in either younger patients (HR, 0.99; P = .98) or older patients (HR, 1.42; P = .33). These findings indicate that MDS[m+] in NPM1 [+] AML is not independently associated with adverse risk after adjusting for age, and highlight the need for age-adjusted AML risk models.

Acute myeloid leukemia (AML) is a group of genetically and clinically heterogeneous malignancies characterized by clonal expansion of immature myeloid progenitors and profound disruption of normal hematopoiesis. Emerging evidence suggests that alterations in cellular homeostasis shape cancer progression. However, the mechanisms underlying AML progression remain largely unclear. Here, we identify lysophosphatidylcholine acyltransferase 3 (LPCAT3), a key enzyme of the Lands' cycle, as a critical regulator of AML progression. Analysis of public transcriptomic datasets and patient-derived CD34[+] cells revealed robust LPCAT3 overexpression in AML and an association between high LPCAT3 levels and inferior overall AML patient survival. Suppression of LPCAT3 by shRNA or CRISPR-Cas9 in MOLM-13 and THP-1 cells markedly impaired proliferation, induced apoptosis, and caused G0/G1 cell-cycle arrest. Conversely, enforced overexpression promoted cell survival. In xenograft murine models, LPCAT3 depletion reduced leukemic burden. RNA-seq following LPCAT3 loss showed that genes differentially expressed were significantly enriched in granulocyte chemotaxis-related pathways, suggesting a role of LPCAT3 in modulation of leukemic differentiation programs and microenvironmental interactions. Collectively, these data established that LPCAT3 as a previously unrecognized mediator of AML cell fitness and as a potential therapeutic target.