Ginsenoside Rh2 promotes cell apoptosis in T-cell acute lymphocytic leukaemia by MAPK and PI3K/AKT signalling pathways.

T-cell acute lymphoblastic leukaemia (T-ALL) is a common childhood malignant tumour, which has poor prognosis and high recurrence rate. Ginsenoside Rh2 (GRh2), a bioactive ingredient of has significant anti-tumour effect. In this study, we found that gene expressions of Jurkat cells were significantly changed in the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) signalling pathways after 35 µm GRh2 treatment, involving in JUN, PIEN, AKT3 and MAPK8IP2.

MLL1 promotes placental trophoblast ferroptosis and aggravates preeclampsia symptoms through epigenetic regulation of RBM15/TRIM72/ADAM9 axis.

This study explores the epigenetic mechanism of MLL1 regulating trophoblast ferroptosis in preeclampsia (PE). A murine model of PE was established, and HTR-8/SVneo cells were induced by Erastin to establish an in vitro cell model. GSH, MDA, Fe, and ROS levels were measured to assess ferroptosis.

A human-like glutaminase-free asparaginase is highly efficacious in ASNS leukemia and solid cancer mouse xenograft models.

L-asparaginase (L-ASNase) is crucial in treating pediatric acute lymphoblastic leukemia (ALL), but its use is hampered by side effects from the immunogenicity and L-glutaminase (L-GLNase) co-activity of FDA-approved bacterial L-ASNases, often leading to treatment discontinuation and poor outcomes. The toxicity of these L-ASNases makes them especially challenging to use in adult cancer patients. To overcome these issues, we developed EBD-200, a humanized guinea pig L-ASNase with low Km and no L-GLNase activity, eliminating glutamine-related toxicity.

Application of Flow Cytometry Immunophenotypic Analysis for the Diagnosis of Mature B-Cell Lymphomas/Leukemias.

Flow cytometry immunophenotypic analysis is an important and indispensable tool in the diagnosis of mature B-cell lymphomas/leukemias, particularly for small fine needle aspiration and needle core biopsy specimens which are becoming increasingly popular for diagnostic purposes. Flow cytometry immunophenotyping (FCI) has several advantages. Given its multiparametric nature, FCI can analyze the expression of multiple antigens simultaneously on the same cell of interest, qualitatively and quantitively.

Histone acetylation alteration by KAT6A inhibitor WM-1119 suppresses IgE-mediated mast cell activation and allergic inflammation via reduction in AP-1 signaling.

Activation of immunoglobulin E (IgE)-associated mast cells (MCs) triggers the onset of pro-inflammatory signals associated with type I allergic diseases. Although histone acetylation changes have been associated with inflammatory diseases, the impact of lysine-acetyltransferase (KAT) inhibitors on IgE-mediated MCs function is unclear. Potential anti-allergic effects of the KAT6A inhibitor WM-1119 on IgE-mediated MCs activation and allergic inflammation were examined in this study.

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.

Chemical dissection of selective myeloid leukemia-1 inhibitors: How they were found and evolved.

Myeloid cell leukemia-1 (MCL-1), a key anti-apoptotic protein within the BCL-2 family, is essential in regulating cell survival, particularly in cancer, where its overexpression is often linked to therapeutic resistance. This review begins with an overview of BCL-2-mediated apoptosis, highlighting the pivotal role of MCL-1 in cellular homeostasis. We then focus on the structure and function of MCL-1, elucidating how its unique structural features contribute to its function and interaction with pro-apoptotic proteins.

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.

Derivatives of D(-)-glutamine-based MMP-2 inhibitors as an effective remedy for the management of chronic myeloid leukemia-Part-III: Synthesis, biological screening and in silico binding interaction analysis.

Tyrosine kinase inhibitors (TKIs) have markedly improved the overall survival rate of patients with chronic myeloid leukemia (CML), enabling them to achieve a normal life expectancy. However, toxicity, relapse, and drug resistance continue to pose major challenges in the clinical treatment of CML. The progression of leukemia is directly connected to higher expression levels and enzymatic actions of matrix metalloproteinase-2 (MMP-2).

Exosome-mediated delivery of CRISPR-Cas9: A revolutionary approach to cancer gene editing.

Several molecular strategies based on targeted gene delivery systems have been developed in recent years; however, the CRISPR-Cas9 technology introduced a new era of targeted gene editing, precisely modifying oncogenes, tumor suppressor genes, and other regulatory genes involved in carcinogenesis. However, efficiently and safely delivering CRISPR-Cas9 to cancer cells across the cell membrane and the nucleus is still challenging. Using viral vectors and nanoparticles presents issues of immunogenicity, off-target effects, and low targeting affinity.

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.

Epstein-Barr virus-associated lymphoproliferative disease during remission after induction therapy with dasatinib in Philadelphia chromosome-positive acute lymphoblastic leukemia: a case report.

Dasatinib, a second-generation tyrosine kinase inhibitor, has been reported to have immunomodulatory effects. Epstein-Barr virus (EBV)-associated lymphoproliferative disorders (EBV-LPD) occur in immunocompromised patients, such as those receiving methotrexate or other immunosuppressive drugs or after allogenic transplantation. EBV-LPD is also reported to be a rare side effect in patients receiving long-term dasatinib or imatinib.

Post-transplant relapse in pediatric acute lymphoblastic leukemia in the era of CAR-T cell therapy. A multicenter analysis of Grupo Español de Trasplante Hematopoyetico y Terapia Celular (GETH-TC) Pediatric Committee.

Background: The management of relapsed acute lymphoblastic leukemia (ALL) after hematopoietic stem cell transplantation (HSCT) has evolved significantly. Initially, treatment options were limited to palliative care, salvage chemotherapy, and second HSCT. Currently, the focus has shifted to innovative immunotherapies, particularly CAR T-cell therapy.

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.

Development and alpha-testing of a patient decision aid for patients with chronic myeloid leukemia regarding dose reduction.

Background: Dose reduction of tyrosine kinase inhibitors (TKIs) is an option for some chronic myeloid leukemia (CML) patients to minimize side effects while maintaining efficacy. Shared decision-making (SDM) and patient decision aids (PDAs) are advocated to make informed choices such as reducing the dose of TKIs. This paper describes the development and alpha-testing of a PDA for patients with CML receiving TKI dose reduction.

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.

Genetic susceptibility of diffuse large B-cell lymphoma: a meta genome-wide association study in Asian population.

Diffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy and the most common form of non-Hodgkin lymphoma (NHL) that occurs worldwide. To discover risk factors and pathogenesis of DLBCL, we performed the largest GWAS of DLBCL to date in samples of East Asian ancestry, consisting of 2,888 patients with DLBCL and 12,458 controls. The meta-analysis identified three novel loci, rs2233434 on 6p21.

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.

Population Pharmacokinetics of Ledipasvir/Sofosbuvir in Pediatric Patients: Impact of Acute Lymphoblastic Leukemia.

Purpose: The pharmacokinetic (PK) profile of direct-acting antivirals, namely ledipasvir/sofosbuvir (LDV/SOF), might be altered in patients with acute lymphoblastic leukemia (ALL), affecting the optimum dose needed for hepatitis C virus treatment. Limited data are available evaluating the population PK of LDV/SOF and SOF metabolite GS-331007. We aimed to study whether ALL could affect population PK parameters of LDV, SOF, and the SOF major metabolite GS-331007 in hepatitis C virus-infected children, develop and validate a predictive PK model of LDV/SOF disposition in this special population, and identify their explained and unexplained sources of variability.

[Vaccination of children and adolescents treated for acute leukemia, excluding HSCT recipients: Recommendations of the French Society for Childhood and Adolescent Cancer and Leukemia (SFCE)].

Children and adolescents who are being treated or have been treated for acute leukemia have a secondary immunodeficiency linked to chemotherapy, resulting in an increased risk of infections. Some of which can be prevented by vaccination but its effectiveness is not optimal during chemotherapy. Upon cessation of chemotherapy, the time required for immune reconstitution varies from three months to more than a year, depending on lymphocyte subpopulations, the patient's age, and the intensity of the treatment received.

Circular RNAs as a new perspective in the diagnosis and mechanism of Leishmania infections.

Leishmaniasis is a neglected infectious disease that affects millions of people worldwide. Visceral leishmaniasis (VL) caused by Leishmania infantum and cutaneous leishmaniasis (CL) caused by L. major/ L.