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American Journal of Hematology Apr 2024Incidence of potential targetable genetic abnormalities by age in AML.
Incidence of potential targetable genetic abnormalities by age in AML.
Topics: Humans; Leukemia, Myeloid, Acute
PubMed: 38361282
DOI: 10.1002/ajh.27236 -
Zhongguo Shi Yan Xue Ye Xue Za Zhi Feb 2024To investigate the effect of expression on the proliferation and the accumulation of intracellular drug of HL60/A and HL60 cells and its possible molecular mechanism.
OBJECTIVE
To investigate the effect of expression on the proliferation and the accumulation of intracellular drug of HL60/A and HL60 cells and its possible molecular mechanism.
METHODS
Lentiviral transfection technology was used to construct HL60/A and HL60 cells with knocked down or overexpressed and their control cells. The efficiency of knockdown and overexpression was evaluated by Western blot. The cell proliferation was detected by CCK-8 assay. The intracellular drug accumulation was detected by laser confocal detection and flow cytometry. The expression levels of MRP1, P-gP and p-AKT were evaluated by flow cytometry and Western blot.
RESULTS
After was knocked down,the proliferation ability of HL60/A cells was significantly reduced, the accumulation of intracellular drug was significantly increased and the expression of MRP1 and P-gP protein were decreased. After was overexpressed, the proliferation ability of HL60 was significantly increased, the accumulation of intracellular drug was significantly decreased and the expression of MRP1 and P-gP protein were increased. Intervention of LY294002 significantly antagonized the promotion on cell proliferation, the inhibition on intracellular drug accumulation and the expression of MRP1 and P-gP mediated by overexpressing in HL60 cells.
CONCLUSION
can promote cell proliferation, improve the expression of MRP1 and P-gP by activating PI3K/AKT signal, and reduce intracellular drug accumulation.
Topics: Humans; HL-60 Cells; Proto-Oncogene Proteins c-akt; Drug Resistance, Neoplasm; Phosphatidylinositol 3-Kinases; Cell Proliferation; Chaperonin Containing TCP-1
PubMed: 38387902
DOI: 10.19746/j.cnki.issn.1009-2137.2024.01.012 -
Biomeditsinskaia Khimiia Dec 2023Plasma membrane proteins with extracellular-exposed domains are responsible for transduction of extracellular signals into intracellular responses, and their...
Plasma membrane proteins with extracellular-exposed domains are responsible for transduction of extracellular signals into intracellular responses, and their accessibility to therapeutic molecules makes them attractive targets for drug development. In this work, using omics technologies and immunochemical methods, we have studied changes in the content of markers of clusters of differentiation (CD markers) of neutrophils (CD33, CD97, CD54, CD38, CD18, CD11b, CD44, and CD71) at the level of transcripts and proteins in NB4, HL-60 and K562 cell lines, induced by the treatment with all-trans-retinoic acid (ATRA). Transcriptomic analysis revealed the induction of CD38, CD54, CD11b, and CD18 markers as early as 3 h after the addition of the inducer in the ATRA-responsive cell lines HL-60 and NB4. After 24 h, a line-specific expression pattern of CD markers could be observed in all cell lines. Studies of changes in the content of CD antigens by means of flow cytometry and targeted mass spectrometry (MS) gave similar results. The proteomic profile of the surface markers (CD38, CD54, CD11b, and CD18), characteristic of the NB4 and HL-60 lines, reflects different molecular pathways for the implementation of ATRA-induced differentiation of leukemic cells into mature neutrophils.
Topics: Humans; Leukemia, Promyelocytic, Acute; Proteomics; Tretinoin; HL-60 Cells; Cell Differentiation
PubMed: 38153053
DOI: 10.18097/PBMC20236906383 -
Cureus Mar 2024The ABO system is an essential blood group in clinical transfusion medicine implicated in several human diseases. The ABO system has been investigated for over a... (Review)
Review
The ABO system is an essential blood group in clinical transfusion medicine implicated in several human diseases. The ABO system has been investigated for over a century, with various studies exploring potential links to disease susceptibility. The study examines the possible relationship between leukemia and the distribution and the ABO blood group system discrepancy. A comprehensive review was conducted on the recommended databases to review the ABO blood groups, their association with leukemia, and the expected changes in blood groups among leukemia patients. The study highlights different kinds of leukemia, such as acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), chronic myeloid leukemia (CML), and chronic lymphocytic leukemia (CLL), their characteristics, and their relationship with ABO blood groups. The document concludes that studying ABO blood group distributions among leukemia patients showed that the most common blood group in acute leukemia is the A group, while in chronic leukemia, the O group is predominant; more studies are required. This study also confirmed an association between leukemia and ABO blood group discrepancy.
PubMed: 38654809
DOI: 10.7759/cureus.56812 -
Journal of Biochemical and Molecular... Nov 2023Acute myeloid leukemia (AML) is a deadly hematologic malignancy. In this study, miR-361-3p and BTG2 gene expression in AML blood and healthy specimens were analyzed...
Acute myeloid leukemia (AML) is a deadly hematologic malignancy. In this study, miR-361-3p and BTG2 gene expression in AML blood and healthy specimens were analyzed using quantitative real-time reverse transcription polymerase chain reaction. A significant negative correlation between miR-361-3p and BTG2 was observed. The cell viability and apoptosis were measured by CCK-8 assay, EdU incorporation assay and flow cytometry. A dual-luciferase reporter gene assay was performed to confirm the binding sequence between miR-361-3p and BTG2 messenger RNA 3'-untranslated region. 9s-Hydroxyoctadecadienoic acid (9s-HODE), a major active derivative of linoleic acid, reduced the viability and induced cell apoptosis of HL-60 cells. Furthermore, the miR-361-3p mimics and siBTG2 reversed the above effects of 9s-HODE. 9s-HODE exerted an anti-AML effect through, at least partly, regulating the miR-361-3p/BTG2 axis.
Topics: Humans; MicroRNAs; Linoleic Acid; Cell Proliferation; Leukemia, Myeloid, Acute; HL-60 Cells; Apoptosis; Cell Line, Tumor; Immediate-Early Proteins; Tumor Suppressor Proteins
PubMed: 37497988
DOI: 10.1002/jbt.23481 -
Transfusion Medicine and Hemotherapy :... Dec 2023In patients with a clinical indication for autologous hematopoietic stem cell transplantation (ASCT), sufficient mobilization of CD34 precursor cells into peripheral...
A German-Wide Systematic Study on Mobilization and Collection of Hematopoietic Stem Cells in Poor Mobilizer Patients with Multiple Myeloma prior to Autologous Stem Cell Transplantation.
INTRODUCTION
In patients with a clinical indication for autologous hematopoietic stem cell transplantation (ASCT), sufficient mobilization of CD34 precursor cells into peripheral blood is essential to ensure adequate hematopoietic stem cell (HSC) collection prior to intensive therapy. However, with standard granulocyte-colony stimulating factor (G-CSF)-based mobilization schemes, an important minority of patients fail to mobilize sufficient (e.g., >10/µL) CD34 cell counts into the peripheral blood and are considered as poor mobilizers (PM). Because failure to achieve sufficient CD34 cell mobilization can negatively affect important clinical treatment endpoints, the use of plerixafor (PLX) was approved to increase CD34 mobilization in PM patients.
METHODS
The German non-interventional, multicenter, open-label, prospective OPTIMOB study evaluated HSC mobilization strategies prior to planned ASCT in adult patients with hematologic malignancies (lymphomas or multiple myeloma [MM]) focusing on PM patients. PM patients were defined as follows: (1) never achieving ≥20 CD34 cells/µL before 1st apheresis, (2) receiving PLX at any timepoint of mobilization, (3) their initially planned stem cell yield had to be reduced, or (4) they had not received apheresis due to low CD34 count in peripheral blood.
RESULTS
168 of 475 MM patients (35%) participating in the OPTIMOB study were classified as PM, and 155 of them (92%) received PLX (PM+PLX) during the study. PM patients were 40-78 years old, slightly more often male ( = 97, 58%), mostly newly diagnosed ( = 146, 87%) and received highly individualized previous treatments. Ninety-four of the PMs underwent chemotherapy mobilization (65%), and 51 patients (35%) received steady-state mobilization with G-CSF only during 1st mobilization attempt. 92% of the total PM population ( = 155) underwent apheresis, 78% of them ( = 117) achieved >2.0 × 10 CD34 cells/kg body weight on the 1st day of apheresis. PM+PLX had a higher median total collection result than those PM patients without PLX support (7.2 vs. 5.7 × 10 CD34 cells/kg body weight). In total, ASCT was performed in 136 PM+PLX (88%) versus 8 PM-PLX patients (62%).
CONCLUSION
The OPTIMOB study showed that a considerable proportion of adult MM patients in Germany are PMs. Even though most of PMs were supported with PLX in the OPTIMOB study, PM-PLX also successfully mobilized HSCs, allowing ASCT in majority of all PMs. However, further analyses are required for treatment optimization in PMs.
PubMed: 38089497
DOI: 10.1159/000531935 -
Cureus Jan 2024Hematopoietic stem-cell transplantation (HSCT) has emerged as a groundbreaking therapeutic option for acute myeloid leukemia (AML) and specific subtypes of acute... (Review)
Review
The Potential Role of NOD2/CARD15 Genotype as a Prognostic Indicator for Bone Marrow Transplantation Outcomes in Patients With Acute Lymphoblastic Leukemia and Acute Myeloid Leukemia: A Systematic Review.
Hematopoietic stem-cell transplantation (HSCT) has emerged as a groundbreaking therapeutic option for acute myeloid leukemia (AML) and specific subtypes of acute lymphoblastic leukemia (ALL). The prognostic significance of the NOD2/CARD15 gene has been explored alongside various factors, encompassing diverse patient cohorts and gene variants. Siblings and unrelated donors used for stem cell transplantation exhibit significant associations between their genetic variations and graft-versus-host disease incidence. The transplantation of stem cells for leukemia patients involves numerous considerations, including patient survival, relapse rates, disease stage, donor and recipient ages, and compatibility. This study delved into research on the NOD2/CARD15 gene and its mutations to assess its suitability as a screening tool. A comprehensive literature search encompassing PubMed, ScienceDirect, and Google Scholar articles yielded 4,840 articles. After removing duplicates and applying inclusion and exclusion criteria, we narrowed the search results to 876 articles. Subsequent screening of abstracts and titles resulted in the selection of 230 relevant articles. Further exclusion of 198 articles unrelated to the research question led to the scrutinizing of 32 full-text articles, which were assessed against inclusion and exclusion criteria. Emphasis was placed on articles that specifically investigated the role of NOD2/CARD15 as a predictive factor for HSCT outcomes, ultimately resulting in the inclusion of 19 articles in this study. Single nucleotide polymorphisms (SNPs) such as NOD2 and CARD15 have demonstrated their potential as reliable genetic markers for predicting post-transplantation relapse and disease outcomes. Patients positive for these genetic markers have exhibited reduced overall survival and event-free survival and increased transplant-related mortality. Interventions with interferon-gamma and muramyl tripeptide phosphatidylethanolamine have been considered to mitigate the inflammatory effects of these SNPs, thus enhancing the influence of natural killer cells on abnormal cells and potentially extending patient survival. NOD2/CARD15 typing may aid in identifying patients at higher risk for relapse and improving their clinical outcomes after allogeneic stem cell transplant, particularly in ALL patients. However, no remarkable change was observed in AML patients. Additionally, this study underscores the pivotal roles of adaptive and innate immune responses and their interplay in stem cell transplant immunology.
PubMed: 38361685
DOI: 10.7759/cureus.52329 -
International Journal of Molecular... Dec 2023Chalcones and their derivatives, both natural and synthetic, exhibit diverse biological activities. In this study, we focused on designing and synthesizing...
Chalcones and their derivatives, both natural and synthetic, exhibit diverse biological activities. In this study, we focused on designing and synthesizing ()-2,4-dichloro--(4-cinnamoylphenyl)-5-methylbenzenesulfonamides - with the following two pharmacophore groups: 2,4-dichlorobenzenesulfonamide and chalcone. The obtained compounds displayed notable anticancer effects on various human cancer cells, such as cervical HeLa, acute promyelocytic leukemia HL-60, and gastric adenocarcinoma AGS, when assessed with the MTT test. The activity of all compounds against cancer cells was significant, and the obtained IC values were in the range of 0.89-9.63 µg/mL. Among all the tested compounds, derivative showed the highest activity on the AGS cell line. Therefore, it was tested for cell cycle inhibition, induction of mitochondrial membrane depolarization, and activation of caspase-8 and -9. These results showed that this compound strongly arrested the cell cycle in the subG0 phase, depolarized the mitochondrial membrane, and activated caspase-8 and -9. Similar to the anticancer effects, all the obtained compounds were also assessed for their antioxidant activity. The highest antiradical effect was demonstrated for derivative , which was able to inhibit DPPH and ABTS radicals. All examined compounds showed dose-dependent activity against neutrophil elastase. Notably, derivatives and demonstrated inhibitory properties similar to oleanolic acid, with IC values of 25.61 ± 0.58 and 25.73 ± 0.39 µg/mL, respectively. To determine the antibacterial activity of derivatives -, the minimum bacteriostatic concentration (MIC) values were estimated (>500 µg/mL for all the tested bacterial strains). The findings demonstrate the substantial potential of sulfonamide-based chalcone as a promising drug in anticancer therapy.
Topics: Humans; Chalcone; Chalcones; Antioxidants; Caspase 8; HL-60 Cells
PubMed: 38203445
DOI: 10.3390/ijms25010274 -
Toxicology and Applied Pharmacology Oct 2023Modern toxicology's throughput has dramatically increased due to alternative models, laboratory automation, and machine learning. This has enabled comparative studies...
Modern toxicology's throughput has dramatically increased due to alternative models, laboratory automation, and machine learning. This has enabled comparative studies across species and assays to prioritize chemical hazard potential and to understand how different model systems might complement one another. However, such comparative studies of high-throughput data are still in their infancy, with more groundwork needed to firmly establish the approach. Therefore, this study aimed to compare the bioactivity of the NIEHS Division of Translational Toxicology's (DTT) 87-compound developmental neurotoxicant (DNT) library in zebrafish and an in vitro high-throughput cell culture system. The early life-stage zebrafish provided a whole animal approach to developmental toxicity assessment. Chemical hits for abnormalities in embryonic zebrafish morphology, mortality, and behavior (ZBEscreen™) were compared with chemicals classified as high-risk by the Cell Health Index (CHI™), which is an outcome class probability from a machine learning classifier using 12 parameters from the SYSTEMETRIC® Cell Health Screen (CHS). The CHS was developed to assess human toxicity risk using supervised machine learning to classify acute cell stress phenotypes in a human leukemia cell line (HL60 cells) following a 4-h exposure to a chemical of interest. Due to the design of the screen, the zebrafish assays were more exhaustive, yielding 86 total bioactive hits, whereas the SYSTEMETRIC® CHS focusing on acute toxicity identified 20 chemicals as potentially toxic. The zebrafish embryonic and larval photomotor response assays (EPR and LPR, respectively) detected 40 of the 47 chemicals not found by the zebrafish morphological screen and CHS. Collectively, these results illustrate the advantages of using two alternative models in tandem for rapid hazard assessment and chemical prioritization and the effectiveness of CHI™ in identifying toxicity within a single multiparametric assay.
Topics: Animals; Humans; Zebrafish; Biological Assay; HL-60 Cells; Larva; Leukemia
PubMed: 37604412
DOI: 10.1016/j.taap.2023.116659 -
Indian Journal of Pathology &... Apr 2024
Topics: Humans; Bone Marrow; Granulocyte Precursor Cells; Histocytochemistry; Inclusion Bodies; Microscopy
PubMed: 38391365
DOI: 10.4103/ijpm.ijpm_33_22