Introduction: CLL is one of the most common leukemias, which is categorized by the accumulation of mature CD5+ B-lymphocytes in the peripheral blood, bone marrow, and secondary lymphoid organs. In this study, the status of rs6449182 polymorphism of the CD38 gene and its association with clinical and laboratory parameters of CLL patients was evaluated. Methods: Genomic DNA extraction was performed using the salting out method. The CD38 gene polymorphism (rs6449182) was studied in 70 patients with CLL and 70 healthy individuals using the PCR-RFLP method. Results: The results of this study showed that the control group had 86% wildtype rs6449182 (CC), 12% heterozygous (CG), and 2% homozygous (GG) genotypes. In the case group, 62% had wild-type genotype (CC) 26% were heterozygous (CG), and 12% were homozygous (GG). Statistical analysis showed that the heterozygous genotype for the CD38 gene was significantly associated with CLL. It was also understood that this polymorphism had a significant relationship with hemoglobin, age, and organomegaly of patients. Conclusions: The CD38 gene polymorphism of rs6449182 SNP G allele had the highest frequency. Moreover, based on the results, this polymorphism has a significant relationship with organomegaly, which indicates the importance of these markers in the pathogenesis and prognosis of the disease.

Introduction: CD38 is a multifunctional enzyme with a potent Ca2+ mobilizing effect, cyclic ADP-ribose (cADPR), and nicotinic acid adenine dinucleotide phosphate (NAADP). Here, we aimed to demonstrate the role of CD38 in platelets via protein kinase C (PKC)-mediated internalization and activation. Methods: Mouse platelets were used in this study. Thrombin, an agonist of platelet function, provoked a prompt and long-lasting increase in intracellular Ca2+ concentration ([Ca2+]i), resulting from an interplay of multifold Ca2+ mobilizing messengers. The signaling pathway was delineated using different inhibitors and techniques such as platelet aggregation assay, intracellular calcium measurements, immunoprecipitation, immunoblotting, and flow cytometry. Results: We observed a sequential formation of cADPR and NAADP through CD38 activation by PKC of non-muscle myosin heavy chain IIA (MHCIIA), resulting in phospholipase C (PLC) activation in the thrombin-stimulated platelets. These findings reveal that PKC is fundamental in activating CD38 and elicits a physiological response in the murine platelets. Conclusion: PKC is involved in many signaling pathways. Specifically, PKC is involved in the internalization of CD38 via MHCIIA in CD38+/+ wild-type (WT) and CD38-/-knockout mice (KO). CD38 generates calcium-mobilizing agents that act on specific receptors of the calcium stores. Calcium triggered platelet aggregation while serving as a secondary messenger.

Many investigators have used xenogeneic, especially murine stromal cells and fetal calf serum to maintain and expand human stem cells. The proliferation and expansion of human hematopoietic stem cells in ex vivo culture were examined with the goal of generating a suitable protocol for expanding hematopoietic stem cells for patient transplantation. Using primary fetal liver cells, we established a serum-free culture system to expand human primitive stem/progenitors cells. Non-enriched cord blood CD34+ cells were cultured on a monolayer of mouse primary fetal liver cells in the presence of trombopoietin, flt3/flk2 ligand, and/or stem cell factor, IL-6 and IL-3 under serum-free conditions. After 1 or 2 weeks of culture, cells were examined for clonogenic progenitors and percentage of CD34+ CD38- cells. In the presence of trombopoietin, flt3/flk2 ligand, and stem cell factor, fetal liver cells supported expansion of CD34+ cells more than 10 to 20 fold. In addition, colony forming unit-cell assay was expanded more than 5- and 10-fold after 1 and 2 weeks of culture, respectively. These results strongly suggest that fetal liver cells may be a suitable feeder layer for expansion of hematopoietic progenitors from umbilical cord blood in vitro

Background: CD38 is highly expressed on multiple myeloma (MM) cells and has been successfully targeted by different target therapy methods. This molecule is a critical prognostic marker in both diffuse large B-cell lymphoma and chronic lymphocytic leukemia.Objective: We have designed and generated an anti-CD38 CAR-NK cell applying NK 92 cell line. The approach has potential application as an off-the-shelf strategy for treatment of CD38 positive malignancies.Methods: A second generation of anti-CD38 CAR-NK cell was designed and generated, and their efficacy against CD38-positive cell lines was assessed in vitro. The PE-Annexin V and 7-AAD methods were used to determine the percentage of apoptotic target cells. Flow cytometry was used to measure IFN-γ, Perforin, and Granzyme-B production following intracellular staining. Using in silico analyses, the binding capacity and interaction interface were evaluated.Results: Using Lentivirus, cells were transduced with anti-CD38 construct and were expanded. The expression of anti-CD38 CAR on the surface of NK 92 cells was approximately 25%. As we expected from in silico analysis, our designed CD38-chimeric antigen receptor was bound appropriately to the CD38 protein. NK 92 cells that transduced with the CD38 chimeric antigen receptor, generated significantly more IFN-γ, perforin, and granzyme than Mock cells, and successfully lysed Daudi and Jurkat malignant cells in a CD38-dependent manner.Conclusion: The in vitro findings indicated that the anti-CD38 CAR-NK cells have the potential to be used as an off-the-shelf therapeutic strategy against CD38-positive malignancies. It is recommended that the present engineered NK cells undergo additional preclinical investigations before they can be considered for subsequent clinical trial studies.