Amls

Relapse of acute myeloid leukemia (AML) is highly aggressive and often treatment refractory. We analyzed previously published AML relapse cohorts and found that 40% of relapses occur without changes in driver mutations, suggesting that non-genetic mechanisms drive relapse in a large proportion of cases. We therefore characterized epigenetic patterns of AML relapse using 26 matched diagnosis-relapse samples with ATAC-seq. This analysis identified a relapse-specific chromatin accessibility signature for mutationally stable AML, suggesting that AML undergoes epigenetic evolution at relapse independent of mutational changes...

The treatment of acute myeloid leukemia (AML) remains unsatisfactory, owing to the absence of efficacious therapy regimens over decades. However, advances in molecular biology, including inhibiting the CXCR4/CXCL12 biological axis, have introduced novel therapeutic options for AML. Additionally, self-stimulated phototherapy can solve the poor light penetration from external sources, and it will overcome the limitation that traditional phototherapy cannot be applied to the treatment of AML. Herein, we designed and manufactured a self-stimulated photodynamic nanoreactor to enhance antileukemia efficacy and suppress leukemia recurrence and metastasis in AML mouse models...

Acute myeloid leukemia (AML) is a fatal disease characterized by the accumulation of undifferentiated myeloblasts, and agents that promote differentiation have been effective in this disease but are not curative. Dihydroorotate dehydrogenase inhibitors (DHODHi) have the ability to promote AML differentiation and target aberrant malignant myelopoiesis. We introduce HOSU-53, a DHODHi with significant monotherapy activity, which is further enhanced when combined with other standard-of-care therapeutics. We further discovered that DHODHi modulated surface expression of CD38 and CD47, prompting the evaluation of HOSU-53 combined with anti-CD38 and anti-CD47 therapies, where we identified a compelling curative potential in an aggressive AML model with CD47 targeting...

Mutation of thetumor suppressor gene, TP53 ( tumor protein 53 ), occurs in up to 15% of all patients with acute myeloid leukemia (AML) and is enriched within specific clinical subsets, most notably in older adults, and including secondary AML cases arising from preceding myeloproliferative neoplasm (MPN), myelodysplastic syndrome (MDS), patients exposed to prior DNA-damaging, cytotoxic therapies. In all cases, these tumors have remained difficult to effectively treat with conventional therapeutic regimens. Newer approaches fortreatmentof TP53- mutated AML have shifted to interventions that maymodulate TP53 function, target downstream molecular vulnerabilities, target non-p53 dependent molecular pathways, and/or elicit immunogenic responses...

Coronavirus disease 2019 (COVID-19)-induced pericarditis and pericardial myocarditis are common entities; however, the development of pericardial effusion post-COVID-19 infection has only been reported in about 5% of cases. Rapid and acute progression to pericardial tamponade is uncommon, and progression to effusive constrictive pericarditis (ECP) and pericardial decompression syndrome (PDS) is an even rarer phenomenon. We describe these phenomena in this report to raise awareness and aid clinicians in the early diagnosis and management of these conditions...

Capnocytophaga sputigena is a gram-negative facultatively anaerobic, capnophilic bacterium typically residing in the human oropharyngeal flora. This opportunistic pathogen can cause a wide range of infections, from bacteremia to septic abortion. However, it is exceedingly rare for a patient to present with tonsillitis due to C. sputigena . Herein, we discuss the presentation, hospital course, and clinical trajectory of a patient experiencing complications of tonsillitis related to C. sputigena in the context of acute myeloid leukemia...

Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults and associated with poor prognosis. Unfortunately, most of the patients that achieve clinical complete remission after the treatment will ultimately relapse due to the persistence of minimal residual disease (MRD), that is not measurable using conventional technologies in the clinic. Microfluidics is a potential tool to improve the diagnosis by providing early detection of MRD. Herein, different designs of microfluidic devices were developed to promote lateral and vertical mixing of cells in microchannels to increase the contact area of the cells of interest with the inner surface of the device...

BACKGROUND: The outcome of extramedullary infiltration (EMI) in pediatric acute myeloid leukemia (AML) is controversial, and little is known about the implications of stem cell transplantation (SCT) and gemtuzumab ozogamicin (GO) treatment on patients with EMI. METHODS: We retrieved the clinical data of 713 pediatric patients with AML from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) dataset, and analyzed the clinical and prognostic characteristics of patients with EMI at diagnosis and relapse...

The prognosis of elderly AML patients had not even been improved by using hypomethylating agents; however, synergistic effect of combining azacitidin with venetoclax had resulted in a remarkable therapeutic advance. Our goal was to study the latter treatment with a new dosing regimen in a retrospective/observational study. In our department, we analyzed the data of AML patients who were unfit for curative high-dose treatment and accepted the medication with a fixed-dose of azacitidin and venetoclax combination (AZA-VEN, 100 mg sc for 7 days-100 mg per os continuously)...

INTRODUCTION: Acute myeloid leukemia (AML) patients may receive hypomethylating agents (HMAs) such as decitabine (DAC) as part of their treatment. Not all patients respond to this therapy, and if they do the clinical response may occur only after 3 to 6 courses of treatment. Hence, early biomarkers predicting response would be very useful. METHODS: We retrospectively analyzed a cohort of 22 AML patients who were treated with DAC. Histology of the bone marrow biopsy, pathogenic mutations and methylation status were related to the treatment response...

BACKGROUND: Lysine [K] methyltransferase 2A (KMT2A, previously known as MLL) gene rearrangements are common in acute leukemias of various lineages and are associated with features such as chemotherapy resistance and rapid relapse. KMT2A::CBL is a rare fusion of unknown pathogenesis generated by a unique interstitial deletion of chromosome 11 that has been reported across a wide age range in both acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) patients. The leukemogenic effect of the KMT2A::CBL rearrangement and its association with clinical prognosis have not been well clarified...

OBJECTIVES: Measurable residual disease flow cytometry (MRD-FC) and molecular studies are the most sensitive methods for detecting residual malignant populations after therapy for TP53-mutated acute myeloid leukemia and myelodysplastic neoplasms (TP53+ AML/MDS). However, their sensitivity is limited in suboptimal aspirates or when the immunophenotype of the neoplastic blasts overlaps with erythroids or normal maturing myeloid cells. In this study, we set out to determine if p53 immunohistochemistry (IHC) correlates with MRD-FC and next-generation sequencing (NGS) in the posttherapy setting and to determine the utility of p53 IHC to detect residual disease in the setting of negative or equivocal MRD-FC...

Targeting the metabolic dependencies of acute myeloid leukemia (AML) cells is a promising therapeutical strategy. In particular, the cysteine and methionine metabolism pathway (C/M) is significantly altered in AML cells compared to healthy blood cells. Moreover, methionine has been identified as one of the dominant amino acid dependencies of AML cells. Through RNA-seq, we found that the two nucleoside analogs 8-chloro-adenosine (8CA) and 8-amino-adenosine (8AA) significantly suppress the C/M pathway in AML cells, and methionine-adenosyltransferase-2A (MAT2A) is one of most significantly downregulated genes...

Acute Myeloid Leukemia (AML) is a malignant blood cancer with a high mortality rate. Neutrophil extracellular traps (NETs) influence various tumor outcomes. However, NET-related genes (NRGs) in AML had not yet received much attention. This study focuses on the role of NRGs in AML and their interaction with the immunological microenvironment. The gene expression and clinical data of patients with AML were downloaded from the TCGA-LAML and GEO cohorts. We identified 148 NRGs through the published article. Univariate Cox regression was used to analyze the association of NRGs with overall survival (OS)...

Leukemias and their bone marrow microenvironments undergo dynamic changes over the course of disease. However, little is known about the circulation kinetics of leukemia cells, nor the impact of specific factors on the clearance of circulating leukemia cells (CLCs) from the blood. To gain a basic understanding of CLC dynamics over the course of disease progression and therapeutic response, we apply a blood exchange method to mouse models of acute leukemia. We find that CLCs circulate in the blood for 1-2 orders of magnitude longer than solid tumor circulating tumor cells...

Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults and the second most common among children. AML is characterized by aberrant proliferation of myeloid blasts in the bone marrow and impaired normal hematopoiesis. Despite the introduction of new drugs and allogeneic bone marrow transplantation, patients have poor overall survival rate with relapse as the major challenge, driving the demand for new therapeutic strategies. AML patients with high expression of the very long/long chain fatty acid transporter CD36 have poorer survival and very long chain fatty acid metabolism is critical for AML cell survival...

Acute myeloid leukemia (AML) is driven by complex mutations and cytogenetic abnormalities with profound tumoral heterogeneity, making it challenging to treat. Ten years ago, the 5-year survival rate of patients with AML was only 29% with conventional chemotherapy and stem cell transplantation. All attempts to improve conventional therapy over the previous 40 years had failed. Now, new genomic, immunological, and molecular insights have led to a renaissance in AML therapy. Improvements to standard chemotherapy and a wave of new targeted therapies have been developed...

We report a series of patients with CSF3R-mutant (CSF3Rmut ) atypical chronic myeloid leukemia (aCML), chronic neutrophilic leukemia (CNL) or other hematologic malignancies. We included 25 patients: 5 aCML and 4 CNL CSF3Rmut patients; 1 aCML, 2 CNL, and 2 myelodysplastic/myeloproliferative neoplasm, not otherwise specified patients without CSF3R mutation; and 11 CSF3Rmut patients with other diseases [8 acute myeloid leukemia (AML), 1 chronic myelomonocytic leukemia (CMML), 1 myelodysplastic syndrome (MDS), and 1 acute lymphoblastic leukemia (ALL)]...

Machine learning (ML) provides a great opportunity for the construction of models with improved accuracy in classical molecular dynamics (MD). However, the accuracy of a ML trained model is limited by the quality and quantity of the training data. Generating large sets of accurate ab initio training data can require significant computational resources. Furthermore, inconsistent or incompatible data with different accuracies obtained using different methods may lead to biased or unreliable ML models that do not accurately represent the underlying physics...

BACKGROUND: Poly ADP-ribose polymerase (PARP) inhibitors are approved for the treatment of some men with advanced prostate cancer. Rare but serious side effects include myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). The impact of PARP inhibitors on clonal hematopoiesis (CH), a potential precursor lesion associated with MDS and AML, is incompletely understood in prostate cancer. We hypothesized that PARP inhibitors would increase CH prevalence and abundance. METHODS: We prospectively enrolled participants with advanced prostate cancer treated with PARP inhibitors...