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.

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.

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.

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.

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.

Howell-Jolly Body-Like Neutrophil Inclusions Following Hematopoietic Stem Cell Transplantation: A Case Report.

BACKGROUND In several studies, the presence of Howell-Jolly body-like inclusions within neutrophils has been observed in cases of HIV infection, SARS-CoV-2 infection, post-transplant immunosuppression, and during chemotherapy or antiviral therapy. The phenomenon of neutrophils exhibiting Howell-Jolly body-like inclusions on peripheral blood smears can be attributable to viral infections or the pharmacological effects of medications. CASE REPORT A 14-year-old male patient who had received a diagnosis of lymphoblastic leukemia a year ago underwent hematopoietic stem cell transplantation and was readmitted due to a recurrence of gastrointestinal graft-versus-host disease (GVHD).

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.

Tocilizumab for Cystoid Macular Edema Secondary to Immune Recovery Uveitis in a Patient with Contraindications to Long-Term Systemic Corticosteroid.

: To report a case of cystoid macular edema (CME) secondary to immune recovery uveitis (IRU) in a patient with previous history of cytomegalovirus (CMV) retinitis and leukemia, which was successfully treated with tocilizumab (TCZ), an interleukin-6 (IL-6) receptor antagonist. : The clinical records of the case were reviewed, focusing on demographics, image findings, and clinical course. : A 17-year-old female with a past medical history of T-cell acute lymphoblastic leukemia (T-ALL) undergoing chemotherapy for two years presented with active CMV retinitis.

Clinical Outcomes of Pediatric Cancer Patients with COVID-19: A Cross-Sectional Study.

Considering the widespread COVID-19 pandemic and its impact, especially on children, particularly those with cancer, in terms of transmission risk, mortality, and the occurrence of the disease based on various studies in different countries, we decided to conduct this study to improve the care of children with cancer regarding COVID-19. A descriptive cross-sectional study with a confirmed diagnosis of COVID-19 consisted of obtaining 20 mL of blood samples from the participants in a random manner. Diagnostic examinations, including CT scans, chest X-rays, and a range of hematologic and blood tests, such as complete blood count, ESR, CRP, and D-Dimer, were performed on all patients.

Cutaneous Manifestation of Acute Lymphoblastic Leukemia.

Acute lymphoblastic leukemia (ALL) is a hematological neoplasm characterized by the proliferation of immature lymphoblasts. Although it is more common in children, it can also occur in adults, presenting significant clinical challenges. This case describes a 46-year-old male patient with a history of hypertension and dyslipidemia, whose first clinical manifestation of ALL was cutaneous.

Philadelphia Chromosome as a Clinically Favorable Prognostic Factor of B-cell Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma in Transplant-Ineligible Elderly Patients in the Era of Molecular-Targeted Therapy.

Background and objective There is scarce data on the treatment outcomes of B-cell acute lymphoblastic leukemia/lymphoblastic lymphoma (B-ALL/LBL) in elderly patients in the era of tyrosine kinase inhibitors (TKIs), blinatumomab, and inotuzumab ozogamicin. In light of this, we aimed to address this gap in data by conducting this retrospective study. Methods Treatment outcomes were retrospectively evaluated by using data from transplant-ineligible patients aged 65 years or older with newly diagnosed B-ALL/LBL (n=29) at two hospitals in Oita, Japan between 2013 and 2023.

Protocol for CRISPR-Cas9-mediated induction of KMT2A rearrangements in cell line and umbilical cord blood hematopoietic stem and progenitor cells.

KMT2A rearrangements are associated with a poor clinical outcome in infant, pediatric, and adult acute lymphoblastic and myeloid leukemia. Here, we present a protocol to reconstruct chromosomal translocations with different partner genes of KMT2A in vitro. We describe steps for patient-specific single guide RNA (sgRNA) design, optimized sgRNA in vitro transcription, detailed purification of hematopoietic stem and progenitor cells (HSPCs) from umbilical cord blood (UCB), and CRISPR-Cas9 editing of the test cell line K562 as well as UCB HSPCs.

Exploring G Protein-Coupled Receptors in Hematological Cancers.

Hematological cancers, such as lymphomas and leukemias, pose significant challenges in oncology, necessitating a deeper understanding of their molecular landscape to enhance therapeutic strategies. This article critically examines and discusses recent research on the roles of G protein-coupled receptors (GPCRs) in myeloma, lymphomas, and leukemias with a particular focus on pediatric acute lymphoblastic (lymphocytic) leukemia (ALL). By utilizing RNA sequencing (RNA-seq), we analyzed GPCR expression patterns in pediatric ALL samples (aged 3-12 years old), with a further focus on Class A orphan GPCRs.

Methionine Synthase Reductase A66G Variant in Pediatric Acute Lymphoblastic Leukemia Patients.

Background: Methionine synthase reductase, which is encoded by the methionine synthase reductase () gene, plays a crucial role in the methylation reactions and the production of DNA and its epigenetic processes. There was a correlation between the (A66G) polymorphism and the likelihood of developing acute lymphoblastic leukemia (ALL). This study was carried out to investigate the correlation among pediatric ALL cases.

Molecular signatures associated with venous thromboembolism in children with acute lymphoblastic leukemia.

Background: Venous thromboembolism (VTE) is a frequent complication of childhood acute lymphoblastic leukemia (ALL).

Objectives: We aimed to identify molecular markers and signatures of leukemia microenvironment associated with VTE in childhood ALL, by dual-omics approach of gene expression (GEP) and DNA-methylation profiling.

Patients/methods: Eligible children were aged 1-21 years old with newly diagnosed ALL enrolled on the Dana Farber Cancer Institute 16-001 trial with available RNA sequencing data from bone marrow at diagnosis.

Therapeutic drug monitoring, population pharmacokinetics models and external validation of high-dose methotrexate in pediatric acute lymphoblastic leukemia.

Introduction: High-dose MTX is used to treat pediatric acute lymphoblastic leukemia (ALL). The drug has a low therapeutic index and a highly interindividual variability in systemic exposure. These characteristics necessitate dose adjustments and therapeutic drug monitoring protocols, while population pharmacokinetic (POP/PK) models may enable more precise drug dosing.

Clinical outcomes and safety of CAR-T cells in treatment of T-Cell acute lymphoblastic leukemia/lymphoma.

Relapsed or refractory T-cell acute lymphoblastic leukemia/lymphoma (r/r T-ALL/LBL) are frequently aggressive and associated with unfavorable prognoses. Pan-targeted Chimeric Antigen Receptor (CAR) T-cell therapy have shown promising results in clinical trials. In recent years, CD7 CAR T-cell and CD5 CAR T-cell demonstrate effectiveness in treating r/r T-ALL/LBL patients with bone marrow infiltration.

Short-Course Blinatumomab Treatment as a Bridge to Further Salvage Therapy for Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia: A Retrospective Single-Center Study.

Backgroud: The high cost of blinatumomab in full doses of full treatments has led to dose reduction and fewer treatment cycles for most patients in China. With current needs for cost-efficiency and resource management in health care, we retrospectively evaluated the clinical effects of short-course blinatumomab treatment for R/R Ph- B-ALL at our center.

Methods: Blinatumomab was administered with 24-h continuous intravenous infusion (9 μg/day for the first 3 days and 28 μg/day for 6-10 days).

From early methods for DNA diagnostics to genomes and epigenomes at high resolution during four decades - a personal perspective.

In the 1980s, my research career begun with microbial DNA diagnostics at Orion Pharmaceutica in Helsinki, Finland, where I was part of an innovative team that developed novel methods based on the polymerase chain reaction (PCR) and the biotin-avidin interaction. One of our key achievements during this time was the invention of the solid-phase minisequencing method for genotyping single nucleotide polymorphisms (SNPs). In the 1990s, I shifted focus to human genetics, investigating mutations of the 'Finnish disease heritage'.

Clinical Outcomes of Respiratory Syncytial Virus Infection Among Pediatric Immunocompromised Hosts.

Background: Pediatric immunocompromised patients are at an increased risk of severe respiratory syncytial virus (RSV) infection. Here, we aimed to describe the clinical course and outcomes of RSV infection in immunocompromised children.

Methods: This single-center study at St.

Clinical Actionability of the NUDT15 *4 (p.R139H) Allele and Its Association With Hispanic Ethnicity.

Nudix hydrolase 15 (NUDT15) deficiency is strongly associated with thiopurine-induced myelosuppression. Currently, testing for NUDT15 deficiency is based on the genotyping of the most frequent and clinically characterized no-function variants, that is, *2, *3 and *9. The Hispanic/Latino-predominant variant NUDT15 *4 (p.