BLNK (BASH/SLP-65) encodes an adaptor protein that plays an important role in B-cell receptor (BCR) signaling. Loss-of-function mutations in this gene are observed in human pre-B acute lymphoblastic leukemia (ALL), and a subset of Blnk knock-out (KO) mice develop pre-B-ALL. To understand the molecular mechanism of the Blnk mutation-associated pre-B-ALL development, retroviral tagging was applied to KO mice using the Moloney murine leukemia virus (MoMLV). The Blnk mutation that significantly accelerated the onset of MoMLV-induced leukemia and increased the incidence of pre-B-ALL Cebpb was identified as a frequent site of retroviral integration, suggesting that its upregulation cooperates with Blnk mutations. Transgenic expression of the liver-enriched activator protein (LAP) isoform of Cebpb reduced the number of mature B-lymphocytes in the bone marrow and inhibited differentiation at the pre-BI stage. Furthermore, LAP expression significantly accelerated leukemogenesis in Blnk KO mice and alone acted as a B-cell oncogene. Furthermore, an inverse relationship between BLNK and C/EBPβ expression was also noted in human pre-B-ALL cases, and the high level of CEBPB expression was associated with short survival periods in patients with BLNK-downregulated pre-B-ALL. These results indicate the association between the C/EBPβ transcriptional network and BCR signaling in pre-B-ALL development and leukemogenesis. This study gives insight into ALL progression and suggests that the BCR/C/EBPβ pathway can be a therapeutic target.
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http://dx.doi.org/10.1111/cas.15164 | DOI Listing |
J Clin Lab Anal
December 2024
Pediatric Growth and Development Research Center, Institute of Endocrinology Iran University of Medical Sciences, Tehran, Iran.
Background: Acute lymphocytic leukemia (ALL), characterized by uncontrolled growth of abnormal lymphocytes, predominantly affects children. Genetic analysis focusing on genes and microRNAs reveals important information about the biology of ALL, enabling accurate diagnosis and treatment. This study examines gene and microRNA expression in B cell ALL to improve early diagnosis and personalized treatment.
View Article and Find Full Text PDFBiomicrofluidics
December 2024
Department of Biomedical Engineering, University of California, Irvine, California 92697, USA.
Chimeric antigen receptor (CAR) T-cell therapy shows unprecedented efficacy for cancer treatment, particularly in treating patients with various blood cancers, most notably B-cell acute lymphoblastic leukemia. In recent years, CAR T-cell therapies have been investigated for treating other hematologic malignancies and solid tumors. Despite the remarkable success of CAR T-cell therapy, cytokine release syndrome (CRS) is an unexpected side effect that is potentially life-threatening.
View Article and Find Full Text PDFACS Omega
December 2024
Faculty of Pharmaceutical Sciences, Sojo University, 4-22-1 Ikeda, Nishi-ku, Kumamoto 860-0082, Japan.
Targeting nonapoptotic cell death offers a promising strategy for overcoming apoptosis resistance in cancer. In this study, we developed Tat-Ram13, a 25-mer peptide that fuses the NOTCH1 intracellular domain fragment RAM13 with a cell-penetrating HIV-1 TAT, for the treatment of T-cell acute lymphoblastic leukemia with aberrant NOTCH1 mutation. Tat-Ram13 significantly downregulated NOTCH1-target genes in T-ALL cell lines.
View Article and Find Full Text PDFTechnol Cancer Res Treat
December 2024
Department of Life Science Engineering, Faculty of New Sciences and Technologies, University of Tehran, Tehran, Iran.
Objectives: This study developed a drug delivery system (DDS) using folic acid (FA)-functionalized chitosan (CS) and poly (lactic-co-glycolic acid) (PLGA) nanocarriers for targeted sodium butyrate (NB) delivery to leukemia cells (NALM6). The goal was to enhance NB's therapeutic efficacy while reducing its cytotoxicity to non-malignant cells.
Methods: FA-CS-PLGA nanocarriers were synthesized and characterized using Fourier-transform infrared spectroscopy (FT-IR), dynamic light scattering (DLS), zeta potential analysis, transmission electron microscopy (TEM), and thermogravimetric analysis (TGA).
Spectrochim Acta A Mol Biomol Spectrosc
December 2024
Key Laboratory of Energy Catalysis and Conversion of Nanchang, College of Chemistry and Materials, Jiangxi Normal University, Nanchang 330022, PR China. Electronic address:
The development of B-lymphoblastic leukemia is tightly associated with aberrant expression of Pax-5a. This work presented a novel dual signal amplification strategy-based Pax-5a detection method by combining the rolling circle amplification reaction (RCA) and the Entropy-driven toehold-mediated strand displacement (ETSD). Particularly noteworthy is the employed ETSD, which effectively improves the rate and stability of the reaction due to its unique entropy-driven principle.
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