The PROTAC selectively degrading BCL-X inhibits the growth of tumors and significantly synergizes with Paclitaxel.

B-cell lymphoma extra large (BCL-X) is an important anti-apoptotic protein of BCL-2 family. It is frequently overexpressed in various hematologic and solid tumors, often positively correlated with chemotherapy resistance in tumors. However, the clinical development of the small molecule BCL-X inhibitor ABT-263 has been challenged on account of its on-target and dose-limiting toxicity.

Discovery of 3-amide-pyrimidine-based derivatives as potential fms-like tyrosine receptor kinase 3 (FLT3) inhibitors for treating acute myelogenous leukemia.

FLT3-ITD and TKD mutants play a central role in acute myeloid leukemia (AML), making FLT3 an attractive target for AML treatment. To discover next-generation FLT3 inhibitors and gather additional structure-activity relationship (SAR) information, we performed structural modifications of G-749 (denfivontinib) utilizing structure simplification and scaffold hopping strategies. Among these derivatives, MY-10 exhibited the most potent and selective inhibition of MV4-11 cell proliferation, demonstrating potent inhibitory activity against FLT3-ITD (IC = 6.

Discovery of novel XPO1 PROTAC degraders for the treatment of acute myeloid leukemia.

Targeting XPO1 inhibition has emerged as a promising therapeutic strategy in cancer treatment. Despite the numerous XPO1 inhibitors reported to date, no XPO1 degraders have been disclosed. In this study, we reported the design, synthesis and biological characterization of small-molecule XPO1 degraders based upon the proteolysis targeting chimera (PROTAC), marking the first public disclosure of XPO1 degraders.

The increase in the expression of circRNAs may contributes to a poor prognosis in acute myeloid leukemia: A systematic review and meta-analysis.

Objective: The primary methods for defining the prognostic risk of AML patients are cytogenetic and molecular analysis at the time of diagnosis. However, the prognosis of intermediate-risk patients is still not well assessed for biomarkers. The main objective of this meta-analysis is to evaluate the relationship between circRNAs and AML prognosis, to provide a theoretical basis for finding effective prognostic indicators in intermediate-risk patients, and to provide an important scientific basis for the development or revision of WHO practice guidelines and ELN risk classification, and to highlight the importance of continuing to focus on and evaluate the prognostic impact of circRNAs on AML in future studies.

Evaluation of HOTAIR, HOXD8, HOXD9, HOXD11 gene expression levels in Turkish patients with acute and chronic myeloid leukemia: A single center experience.

Homeobox (HOX) transcript antisense RNA (HOTAIR) and HOX genes are reported to be more expressed in various cancers in humans in recent studies. The role of HOTAIR and HOXD genes in acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) is not well known. In this study, expression levels of HOXD8, HOXD9 and HOXD11 from HOXD gene family and HOTAIR were determined from peripheral blood samples of 30 AML and 30 CML patients and 20 healthy volunteers by quantitative Real Time PCR.

Unraveling the interplay of CD8 + T cells and microRNA signaling in cancer: implications for immune dysfunction and therapeutic approaches.

MicroRNAs (miRNAs) emerge as critical regulators of CD8 + T cell function within the complex tumor microenvironment (TME). This review explores the multifaceted interplay between miRNAs and CD8 + T cells across various cancers. We discuss how specific miRNAs influence CD8 + T cell activation, recruitment, infiltration, and effector function.

Targeting protein tyrosine phosphatase non-receptor type 6 (PTPN6) as a therapeutic strategy in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy characterized by the clonal expansion of myeloid progenitor cells. Despite advancements in treatment, the prognosis for AML patients remains poor, highlighting the need for novel therapeutic targets. Protein Tyrosine Phosphatase Non-Receptor Type 6 (PTPN6), also known as SHP-1, is a critical regulator of hematopoietic cell signaling and has been implicated in various leukemias.

SLC25A21 correlates with the prognosis of adult acute myeloid leukemia through inhibiting the growth of leukemia cells via downregulating CXCL8.

In recent years, targeting mitochondrial apoptosis has emerged as a promising therapeutic strategy for Acute Myeloid Leukemia (AML). The SLC25 family of mitochondrial carriers plays a critical role in maintaining mitochondrial function and regulating apoptosis. However, the role of SLC25A21, an oxodicarboxylate carrier, in AML progression and its potential as a prognostic biomarker remain underexplored.

Discovery of pyridine-based derivatives as FLT3 inhibitors for the treatment of acute myeloid leukemia.

FMS-like tyrosine receptor kinase 3 (FLT3) mutations, the most common genetic alterations found in acute myeloid leukemia (AML) patients, have been pursued as an ideal drug discovery target for the AML therapy. Taking compound 2 as lead, a series of pyridine derivatives bearing 1,2,3-triazole moiety were rationally designed and synthesized. The bioassays confirmed that these derivatives exerted potent antileukemia effects, and compound 12y was found to be the most potent one.

A phase 1 study of the CDK9 inhibitor voruciclib in relapsed/refractory acute myeloid leukemia and B-cell malignancies.

The anti-apoptotic protein myeloid cell leukemia-1 (Mcl-1) contributes to the pathophysiology of acute myeloid leukemia (AML) and certain B-cell malignancies. Tumor dependence on Mcl-1 is associated with resistance to venetoclax. Voruciclib, an oral cyclin-dependent kinase (CDK) inhibitor targeting CDK9, indirectly decreases Mcl-1 protein expression and synergizes with venetoclax in preclinical models.

Bone marrow mesenchymal stem cell exosomes suppress JAK/STAT signaling pathway in acute myeloid leukemia in vitro.

Introduction: Despite advances in the treatment of acute myeloid leukemia (AML), refractory forms of this malignancy and relapse remain common. Therefore, development of novel, synergistic targeted therapies are needed urgently. Recently, mesenchymal stem cells (MSCs) have been shown to be effective in treating various diseases, with most of their therapeutic outcomes attributed to their exosomes.

DNMT1 inhibition improves the activity of memory-like natural killer cells by enhancing the level of autophagy.

Background: Acute myeloid leukemia (AML) is a common hematological tumor, but it is difficult to treat. DNMT1 is a DNA methyltransferase whose main function is to maintain stable DNA methylation during the DNA replication process. DNMT1 also plays an important role in AML, but its function in cytokine-induced memory-like natural killer (CIML NK) cell activity remains unclear.

Whole exome sequencing analysis of a patient with myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions with ETV6::LYN fusion gene.

ETV6::LYN fusion gene is recognized as one of the genetic alterations responsible for myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions (MLN-TK) according to the 2022 WHO classification. However, the clinical features and pathogenesis of MLN-TK with ETV6::LYN are not well defined because of the rarity of the disease. Here, we report an MLN-TK patient with ETV6::LYN that manifested as myeloproliferative neoplasms (MPN) with eosinophilia, myelofibrosis, and T-lymphoblastic lymphoma (T-LBL), which eventually led to acute myeloid leukemia.

Inhibitory Effects of the Methanol Extract of the Golden Chanterelle Mushroom, Cantharellus cibarius (Agaricomycetes) in Treating a Human Acute Myeloid Leukemia Cell Line.

Currently available treatments for acute myeloid leukemia exhibit side effects that limit their use, with primary and secondary resistance as persistent issues. While edible mushrooms possess nutritional value, they are also an excellent source of bioactive compounds that may have the potential to treat multiple disease states. The aim of the present study was to investigate the in vitro inhibitory effects of chromatographic fractions from the methanol extract of Cantharellus cibarius in a human acute myeloid leukemia (AML) cell line MV4-11.

FACTORS AFFECTING COVID-19 OUTCOMES IN PATIENTS WITH HEMATOLOGICAL MALIGNANCIES.

Background: Patients with hematological malignancies (HM) are considered to have a high risk of developing severe and life-threatening infections including COVID-19 because of immune deficiency and immunosuppressive treatments. Although the COVID pandemic spread worldwide, morbidity and mortality data varied from country to country. A more accurate identification of risk factors would allow the improvement of the clinical management of HM patients.

Diagnostic challenges of high-grade myeloid malignancies with partial plasmacytoid dendritic cell differentiation: report of two cases with literature review.

The diagnosis of myeloid neoplasms with plasmacytoid dendritic cell (pDC) differentiation can be challenging due to immunophenotypic overlap requiring detailed characterization by flow cytometry and immunohistochemistry. We describe two patients with a history of myeloproliferative neoplasm (MPN) and myelodysplastic/myeloproliferative neoplasm (MDS/MPN) who presented years later with leukocytosis, lymphadenopathy, splenomegaly, and cachexia, with rapid clinical deterioration and death. Lymph node biopsy specimens revealed involvement by myeloid sarcoma with prominent pDC differentiation.

Bleximenib, the novel menin-KMT2A inhibitor JNJ-75276617, impairs long-term proliferation and immune evasion in acute myeloid leukemia.

Acute myeloid leukemia (AML) remains challenging to treat, which in part relates to genetic heterogeneity of the disease, to the protective tumor microenvironment driving resistance to therapy, and also to immune evasion characteristics of leukemic cells. Targeting epigenetic programs in AML provides an attractive opportunity to impair long-term proliferation and induce differentiation. The novel inhibitor JNJ- 75276617 (bleximenib) targets the menin-KMT2A interaction and provides preclinical efficacy in AML (Kwon et al1).

a novel marker associated with poor pediatric AML outcomes that affect the fatty acid synthesis and cell cycle pathways.

Introduction: Despite remarkable progress in Pediatric Acute Myeloid Leukemia (pAML) treatments, the relapsed disease remains difficult to treat, making it pertinent to identify novel biomarkers of prognostic/therapeutic significance.

Material And Methods: Bone marrow samples from 21 pAML patients were analyzed using single cell RNA sequencing, functional assays with knockdown and overexpression were performed in leukemia cell lines to evaluate impact on proliferation and migration, and chemotherapy sensitivity. Mitochondrial function was assessed via Seahorse assay, interacting proteins were studied using co-immunoprecipitation.

Up-Regulation of miR-625-5p Correlates with Suppressed Sox2, Increased Apoptosis, and Cell Cycle Arrest via The PI3K/AKT Signalling Pathway in Acute Myeloid Leukaemia.

Up-regulation of the microRNA-625 and abnormal expression of the Sox2 gene have been studied and seen in several tumors. Few reports have also shown the aberrant expression of miR-625 and Sox2 expression in various cancers. Several studies have also confirmed that phosphatidylinositol 3' -kinase /protein kinase B pathways regulate hematological malignancies, including Acute Myeloid Leukemia (AML).

Research Hotspots and Trends of NK Cell Immunotherapy for Acute Myeloid Leukemia: A Bibliometric Analysis From 2000 to 2023.

Background: Natural killer (NK) cell immunotherapy has shown promising therapeutic potential for acute myeloid leukemia (AML), especially with advancements in chimeric antigen receptor-engineered NK cells (CAR-NK) and artificial intelligence (AI). Despite these developments, the field lacks comprehensive bibliometric analyses to identify research hotspots and trends, which could guide future precision treatments.

Methods: A bibliometric analysis of NK cell immunotherapy for AML was conducted using literature from 2000 to 2023 retrieved from the Web of Science Core Collection database.

ADAR1 is required for acute myeloid leukemia cell survival by modulating post-transcriptional Wnt signaling through impairing miRNA biogenesis.

Recent extensive studies on the genomic and molecular profiles of acute myeloid leukemia (AML) have expanded the treatment options, including, a range of compounds represented by fms-like tyrosine kinase 3 and isocitrate dehydrogenase 1/2 inhibitors. However, despite this progress, further treatments for AML are still required. Adenosine deaminase acting on RNA 1 (ADAR1) has been shown to play an important oncogenic role in many cancers, but its involvement in AML progression remains underexplored.

Comparison of fludarabine/melphalan (FM140) with fludarabine/melphalan/BCNU (FBM110) in patients with relapsed/refractory AML undergoing allogeneic hematopoietic cell transplantation - a registry study on behalf of the EBMT Acute Leukemia Working Party.

The treatment of relapsed/refractory acute myeloid leukemia (AML) is associated with a dismal prognosis. The allogeneic hematopoietic cell transplantation (allo-HCT) is frequently performed as salvage therapy. Reduced intensity conditioning protocols have been developed with the aim of reducing the leukemia burden without increasing their toxicity.

Computational assessment of measurable residual disease in acute myeloid leukemia using mixture models.

Background: The proportion of residual leukemic blasts after chemotherapy assessed by multiparameter flow cytometry, is an important prognostic factor for the risk of relapse and overall survival in acute myeloid leukemia (AML). This measurable residual disease (MRD) is used in clinical trials to stratify patients for more or less intensive consolidation therapy. However, an objective and reproducible analysis method to assess MRD status from flow cytometry data is lacking, yet is highly anticipated for broader implementation of MRD testing.