Mutations in protein tyrosine phosphatase non-receptor type 11 ( ) have been considered late acquired mutations in acute myeloid leukemia (AML) development. To interrogate the ontogeny of mutations, we utilized single-cell DNA sequencing and identified that mutations can occur as initiating events in some AML patients when accompanied by strong oncogenic drivers, commonly mutations. The co-driver role of mutations was confirmed in a novel murine model that exhibits an AML phenotype with early expansion of a diverse set of variably differentiated myeloid cells that engrafted into immunodeficient and immunocompetent mice. This immune diversity was reconstituted from early precursor cells when engrafted into immunodeficient mice. Moreover, immune diversity was also observed in the blast component of patient samples with and mutations, providing novel antigen targets for immune based approaches in this subset of AML that is resistant to multiple targeted therapies.
Acute liver failure (ALF) is a life-threatening clinical syndrome characterized by high-grade inflammation and multi-organ failure. Our previous study shows that targeting the M2 isoform of pyruvate kinase (PKM2) to inhibit macrophage inflammation may be a promising strategy for ALF treatment. however, the mechanism by which PKM2 regulates the inflammatory response is unclear.
Background: The complexity of acute myeloid leukemia (AML) is increasingly recognized through the identification of distinct subgroups, including those with an APL-like immunophenotype characterized by the absence of CD34 and HLA-DR expression, which is widely recognized as a representative immunophenotype in acute promyelocytic leukemia (APL). This study sought to understand the clinical, molecular, and prognostic differences between AML patients with and without this phenotype.
Methods: This study retrospectively analysed 191 de novo non-M3 AML patients and identified 32 patients with the CD34HLA-DR phenotype resembling APL-like immunophenotype, considered as the experimental group.
Department of Hematology, Taixing People's Hospital Affiliated to Yangzhou University, Taixing, China; Institute of Hematology, affiliated hospital of Yangzhou University, Taixing, China. Electronic address:
Acute myeloid leukemia (AML) is a complex hematological malignancy predominantly affecting the elderly, with a median diagnosis age of 68 years. Despite advances in treatment, elderly AML patients face suboptimal survival outcomes, with an estimated 5-year survival rate below 20 %. Epigenetic dysregulation, notably DNA methylation, is a key factor in the progression of myelodysplastic syndromes (MDS) to AML.
Department of Haematology & Stem Cell Transplantation, West German Cancer Center, University Hospital Essen, Essen, Germany; Laboratory for Clinical Research and Real-World Evidence, Institute for Artificial Intelligence in Medicine, University Hospital Essen, Essen, Germany. Electronic address:
Background: Artificial intelligence (AI) and machine learning (ML) algorithms have shown great promise in clinical medicine. Despite the increasing number of published algorithms, most remain unvalidated in real-world clinical settings. This study aims to simulate the practical implementation challenges of a recently developed ML algorithm, AI-PAL, designed for the diagnosis of acute leukaemia and report on its performance.
Department of Scientific Research, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, China. Electronic address:
Acute myeloid leukemia (AML) is a biologically heterogeneous disease originating from the clonal expansion of hematopoietic stem cells (HSCs). Clonal expansion of hematopoietic stem cell progenitors (HSC-Prog), along with a block in differentiation, are hallmark features of AML. The disease is characterized by poor clinical outcomes, highlighting the urgent need for effective therapeutic strategies and suitable drug targets.
