Plasma concentrations of venetoclax and Pharmacogenetics correlated with drug efficacy in treatment naive leukemia patients: a retrospective study.

Venetoclax (VEN) was the only Bcl-2 inhibitor approved yet and showed large differences in clinical efficacy. The aim of the study was to explore the relationships between the plasma concentration and efficacy of VEN, and identify potential influencing factors. A retrospective cohort study was conducted and a total of 76 trough (C) and 91 6 h post-dose plasma concentration (C) blood concentrations of VEN were collected in 54 patients.

CAR-NK cells for acute myeloid leukemia immunotherapy: past, present and future.

Acute myeloid leukemia (AML) is a deadly disease and the most common leukemia in adult with clonal heterogeneity and abnormity in myeloid lineages, which has been recognized with high morbidity and mortality attributes to the recurrence and resistance to chemotherapy. Numerous literatures have indicated the encouraging progress in allogeneic hematopoietic stem cell transplantation (allo-HSCT) and chimeric antigen receptor-transduced T (CAR-T) cells. However, the outcomes of recurrent and refractory AML (r/rAML) patients with current strategies are still unsatisfactory, which largely due to the matching restriction as well as adverse reactions, including graft-versus-host disease (GvHD), neurotoxicity and cytokine release syndrome (CRS).

Outcomes of venetoclax combined with homoharringtonine and cytarabine in fit adults patients with de novo adverse-risk acute myeloid leukaemia: A single-centre retrospective analysis.

Adverse-risk acute myeloid leukemia (AML) has a dismal prognosis. We aimed to investigate the activity and tolerability of venetoclax combined with homoharringtonine (HHT) plus cytarabine (VHA) regimen for de novo adverse-risk AML. Thirteen de novo AML patients with adverse-risk factors were treated with venetoclax (100 mg day 1, 200 mg day 2, 400 mg days 3-21), HHT (1 mg/m days 1-5) and cytarabine (100 mg/m days 1-5) (VHA regimen).

Development of a scoring system for predicting primary resistance to venetoclax plus hypomethylating agents (HMAs) in acute myeloid leukemia patients.

In recent years, one of the most promising advances in the treatment of acute myeloid leukemia (AML) is the combination of a hypomethylating agent (HMA) with the BCL2 inhibitor venetoclax (VEN). To better understand the key factors associated with the response of VEN plus HMA, 212 consecutive AML patients were retrospectively recruited to establish and validate a scoring system for predicting the primary resistance to VEN-based induced therapy. All AML patients were divided randomly into a training set (n = 155) and a validation set (n = 57).

Clinical Response to Venetoclax and Decitabine in Acute Promyelocytic Leukemia With a Novel RARA-THRAP3 Fusion: A Case Report.

Variant acute promyelocytic leukemia (APL) showed quite different aspects, and the current treatments remained challenged at present. Venetoclax, a selective inhibitor of B-cell lymphoma 2 (BCL-2), is a small molecule that has been studied in several hematologic malignancies as both monotherapy and in combination with other agents. However, there is little of its use in the treatment of APL or variant APL.

Bone marrow-derived mesenchymal stem/stromal cells in patients with acute myeloid leukemia reveal transcriptome alterations and deficiency in cellular vitality.

Background: State-of-the-art advances have indicated the pivotal characteristics of bone marrow-derived mesenchymal stem/stromal cells (BM-MSCs) in hematopoietic microenvironment as well as coordinate contribution to hematological malignancies. However, the panoramic view and detailed dissection of BM-MSCs in patients with acute myeloid leukemia (AML-MSCs) remain obscure.

Methods: For the purpose, we isolated and identified AML-MSCs together with healthy donor-derived HD-MSCs from the bone marrow mononuclear cells (BM-MNCs) by using the standard density gradient centrifugation based on clinical diagnosis and cellular phenotypic analysis.

[Clinical Significance of Pretransplant Serum Ferritin Level in Patients with Prolonged Thrombocytopenia after Allogeneic Hematopoietic Stem Cell Transplantation].

Objective: To investigate the correlation between pretransplant serum ferritin (SF) level and prolonged or prolonged isolated thrombocytopenia (PT) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Methods: The clinical data of 35 patients with PT after allo-HSCT were retrospectively analyzed, and 35 patients were matched according to age and sex as a controls from 424 allo-HSCT patients with normal platelet count. The serum ferritin level before the transplantation was analyzed.

CD38-directed CAR-T cell therapy: a novel immunotherapy strategy for relapsed acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative treatment for acute myeloid leukemia (AML). However, most patients experience relapse after allo-HSCT, with a poor prognosis, and treatment options are limited. The lack of an ideal targetable antigen is a major obstacle for treating patients with relapsed AML.

Early T-Cell Precursor Acute Lymphoblastic Leukemia and T/Myeloid Mixed Phenotype Acute Leukemia Possess Overlapping Characteristics and Both Benefit From CAG-Like Regimens and Allogeneic Hematopoietic Stem Cell Transplantation.

Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) and T-lymphoid/myeloid mixed phenotype acute leukemia (T/M-MPAL) are closely related entities and remain a therapeutic challenge. In this study, we characterized the clinical features of 43 ETP-ALL and 41 T/M-MPAL patients and compared clinical outcomes and safety between cytarabine, aclarubicin, and granulocyte colony-stimulating factor (CAG)-like regimens in 34 patients and conventional ALL regimens in 50 patients. In our series, ETP-ALL and T/M-MPAL showed similar biological characteristics, immunophenotypes, genomic alterations, and outcomes.

Immune Thrombocytopenia Plasma-Derived Exosomes Impaired Megakaryocyte and Platelet Production through an Apoptosis Pathway.

Reduced megakaryocyte (MK) apoptosis and insufficient platelet production play important roles in the pathogenesis of immune thrombocytopenia (ITP). The contribution of plasma-derived exosomes to the decreased platelet count in ITP has not been entirely understood. Here, we found the percentage of apoptotic MKs in patients with ITP was significantly lower than those in healthy volunteers.

Multifaceted modifications for a cell size-based circulating tumor cell scope technique hold the prospect for large-scale application in general populations.

Circulating tumor cells (CTCs) indicate the diagnosis and prognosis of cancer patients, together with benefiting individual treatment and anticancer drug development. However, their large-scale application in general population still requires systematically multifaceted modifications for currently proprietary new technologies based on filtration. We primitively utilized a cell size-based platform to evaluate the recovery efficiency of spiked abnormal cell lines and analyzed circulating abnormal cells (CACs).

Systematic comparison of hUC-MSCs at various passages reveals the variations of signatures and therapeutic effect on acute graft-versus-host disease.

Background: Mesenchymal stem cells are heterogenous populations with hematopoietic supporting and immunomodulating capacities. Enormous studies have focused on their preclinical or clinical therapeutic effects, yet the systematic study of continuous in vitro passages on signatures and functions of UC-MSCs at both the cellular and molecular levels is still lacking.

Methods: In this study, to systematically evaluate the biological properties of MSCs at various passages, we analyzed biomarker expression, cell proliferation and apoptosis, chromosome karyotype, and tri-lineage differentiation potential.

JNKi- and DAC-programmed mesenchymal stem/stromal cells from hESCs facilitate hematopoiesis and alleviate hind limb ischemia.

Background: Mesenchymal stem/stromal cells (MSCs) derived from human embryonic stem cells (hESCs) are attractive for their hematopoietic-supporting or potential therapeutic effects. However, procedures for high-effective and scalable generation of MSCs from hESCs within 2 weeks are still unestablished, which also hinder the development and mechanism study of mesengenesis.

Methods: In this study, we aimed to establish a strategy for programming hESC differentiation into MSCs by practicing small-scale chemical compound screening.

Intravenous injection of allogeneic umbilical cord-derived multipotent mesenchymal stromal cells reduces the infarct area and ameliorates cardiac function in a porcine model of acute myocardial infarction.

Background: Multipotent mesenchymal stromal cell (MSC) therapy has been widely recognized as a feasible strategy for regenerating injured myocardial tissue. However, little is known about the efficacy of intravenous injection of allogeneic umbilical cord (UC) MSCs in preclinical models of porcine myocardial infarction.

Methods: Different dosages of allogeneic UC-MSCs or the vehicle [phosphate-buffered saline (PBS)] were delivered intravenously into an acute myocardial infarction (AMI) porcine model twice after coronary ligation.

Exosomes from mesenchymal stromal cells enhance imatinib-induced apoptosis in human leukemia cells via activation of caspase signaling pathway.

Background Aims: Imatinib (IM), a tyrosine kinase inhibitor targeting the BCR-ABL oncoprotein, remains a major therapeutic strategy for patients with chronic myelogenous leukemia (CML). However, IM resistance is still a challenge in the treatment of CML. Recently, it was reported that exosomes (Exo) were involved in drug resistance.

Knockdown of IL-8 Provoked Premature Senescence of Placenta-Derived Mesenchymal Stem Cells.

Mesenchymal stem cells (MSCs) have shown promise for use in cell therapy, and due to their tumor tropism can serve as vehicles for delivering therapeutic agents to tumor sites. Because interleukin-8 (IL-8) is known to mediate the protumor effect of MSCs, elimination of IL-8 secretion by MSCs may enhance their safety for use in cancer gene therapy. However, little is known concerning the effect of endogenously secreted IL-8 on MSCs.

Interferon‑γ alters the microRNA profile of umbilical cord‑derived mesenchymal stem cells.

Numerous studies have demonstrated that interferon-γ (IFN-γ) is an important inflammatory cytokine, which may activate the immunomodulatory abilities of mesenchymal stem cells (MSCs), and may influence certain other functions of these cells. MicroRNAs are small non‑coding RNAs that regulate the majority of the biological functions of cells and are important in a variety of biological processes. However, few studies have been performed to investigate whether IFN‑γ affects the microRNA profile of MSCs.

VCAM-1+ placenta chorionic villi-derived mesenchymal stem cells display potent pro-angiogenic activity.

Introduction: Mesenchymal stem cells (MSCs) represent a heterogeneous cell population that is promising for regenerative medicine. The present study was designed to assess whether VCAM-1 can be used as a marker of MSC subpopulation with superior angiogenic potential.

Methods: MSCs were isolated from placenta chorionic villi (CV).