{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T17:34:45Z","timestamp":1777570485395,"version":"3.51.4"},"reference-count":19,"publisher":"ALUNA","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,1]]},"abstract":"<jats:p>Aim: To estimate role of CD38 rs6449182 polymorphism in CLL risk and its effect on the expression of critical tumor suppressor TP53, the promoter of cell adhesion and migration, CD44, and the immune checkpoint molecule PD-L1.\nMaterials and Methods: This case-control study included 50 CLL patients and 50 healthy individuals, age- and sex-matched. CLL diagnosed by flow cytometry (CD5+\/CD19+\/CD23+) based on WHO criteria. Genotyping of the CD38 rs6449182 polymorphism was detected through TaqMan SNP Assay. mRNA expression levels of TP53, CD44, and PD-L1 were quantified using real-time RT-PCR .\nResults: Mutant G-allele was more frequent in CLL patients than in controls (19.0% vs. 10.0%), although this difference was only marginally significant P=0.075. No statistically significant association was observed between specific CD38 genotypes and the regulatory status (upregulation\/downregulation) of the target genes P&gt;0.05, while individuals with GG genotype exhibited higher median fold changes for TP53 (FC=2.97) and CD44 (FC=2.00) than the wild-type, the presence of significant inter-individual variance and broad confidence intervals indicates that these genetic variants do not serve as definitive independent predictors of gene expression in this cohort.\nConclusions: results suggest that the CD38 rs6449182 polymorphism may, at least in part, be involved in CLL risk but that it does not lead to a significant genotype-specific regulatory effect on the fold change of CD44, TP53, or PD-L1 expression. Although CD38 remains an important prognostic biomarker, the absence of a genetic-phenotypic relationship found in this study illustrates the complexity of molecular regulation by CLL. Larger studies are needed to confirm these findings.<\/jats:p>","DOI":"10.36740\/merkur202602101","type":"journal-article","created":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T19:09:48Z","timestamp":1777403388000},"page":"120","source":"Crossref","is-referenced-by-count":0,"title":["CD38 genotype-dependent regulation of CD44 and TP53 links genetic variation to aggressive phenotype in chronic lymphocytic leukemia"],"prefix":"10.36740","volume":"54","author":[{"given":"Maryam A.","family":"Hussain","sequence":"first","affiliation":[{"name":"ZOOLOGY DEPARTMENT, FACULTY OF SCIENCE, MANSOURA UNIVERSITY, MANSOURA, EGYPT; COLLEGE OF HEALTH AND MEDICAL TECHNIQUES\/ BABYLON, AL-FURAT AL-AWSAT TECHNICAL UNIVERSITY, BABYLON, IRAQ"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maggie E.","family":"Amer","sequence":"additional","affiliation":[{"name":"ZOOLOGY DEPARTMENT, FACULTY OF SCIENCE, MANSOURA UNIVERSITY, MANSOURA, EGYPT"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shaimaa","family":"El-Ashwah","sequence":"additional","affiliation":[{"name":"ONCOLOGY CENTER, FACULTY OF MEDICINE, MANSOURA UNIVERSITY, MANSOURA, EGYPT"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Motaz","family":"ElKosairy","sequence":"additional","affiliation":[{"name":"ONCOLOGY CENTER, FACULTY OF MEDICINE, MANSOURA UNIVERSITY, MANSOURA, EGYPT"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasser M.","family":"El-Sherbini","sequence":"additional","affiliation":[{"name":"NAHDA UNIVERSITY, BENI SUEF, EGYPT"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamed","family":"Mabed","sequence":"additional","affiliation":[{"name":"ONCOLOGY CENTER, FACULTY OF MEDICINE, MANSOURA UNIVERSITY, MANSOURA, EGYPT"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamed E.","family":"Abdraboh","sequence":"additional","affiliation":[{"name":"ZOOLOGY DEPARTMENT, FACULTY OF SCIENCE, MANSOURA UNIVERSITY, MANSOURA, EGYPT"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"22436","published-online":{"date-parts":[[2026,4,1]]},"reference":[{"key":"ref0","doi-asserted-by":"crossref","unstructured":"1. Paul P, St\u00fcssi G, Bruscaggin A, Rossi D. Genetics and epigenetics of CLL. Leuk Lymphoma. 2023;64(3): 551-563. doi: 10.1080\/10428194.2022.2153359","DOI":"10.1080\/10428194.2022.2153359"},{"key":"ref1","doi-asserted-by":"crossref","unstructured":"2. Sandoval-Sus JD, Chavez JC, Dalia S, Naqvi SMH, Talati C, Nodzon L, et al. Association between immunoglobulin heavy-chain variable region mutational status and isolated favorable baseline genomic aberrations in chronic lymphocytic leukemia. Leuk Lymphoma. 2018 Jan;59(1):59-68. doi: 10.1080\/10428194.2017.1323271.","DOI":"10.1080\/10428194.2017.1323271"},{"key":"ref2","doi-asserted-by":"crossref","unstructured":"3. Mwangi R, Kleinstern G, Achenbach SJ, Robinson DP, Norman AD, Rabe KG, et al. Abstract 5222: Genetic variants associated with progression from monoclonal B-cell lymphocytosis (MBL) to chronic lymphocytic leukemia (CLL). Cancer Res. 2023 Apr; 83(7_Suppl): 5222. doi: 10.1158\/1538-7445.AM2023-5222.","DOI":"10.1158\/1538-7445.AM2023-5222"},{"key":"ref3","doi-asserted-by":"crossref","unstructured":"4. Sudhahar T, Bains R, Naithani M, Mirza AA, Nath UK, Chandra H, et al. Comprehensive Molecular Genetic and Clinical Profiling in CLL: Role of Del 13q14, 17p13, 11q22, Trisomy 12, TP53, NOTCH1, MYD88, SF3B1, ATM, and IGHV Status - a Real World Data in an Indian Subcontinent. Blood. 2024 Nov; 144(Suppl 1): 6803. doi: 10.1182\/blood-2024-209910.","DOI":"10.1182\/blood-2024-209910"},{"key":"ref4","doi-asserted-by":"crossref","unstructured":"5. Lopresti L, Capitani N, Tatangelo V, Tangredi C, Boncompagni G, Frezzato F, et al. p66Shc deficiency in CLL cells enhances PD-L1 expression and suppresses immune synapse formation. Front Cell Dev Biol. 2024;12:1297116. doi: 10.3389\/fcell.2024.1297116.","DOI":"10.3389\/fcell.2024.1297116"},{"key":"ref5","unstructured":"6. Eyada TK, Farawela HM, Khorshied EN, Selim TH, El-Gammal MM. CD38 gene polymorphism rs6449182 and risk of chronic lymphocytic leukemia in Egyptians. Egypt J Haematol. 2013; 38(4): 173-177. doi: 10.4103\/1110-1067.124507."},{"key":"ref6","doi-asserted-by":"crossref","unstructured":"7. Buggins AG, Levi A, Gohil S, Fishlock K, Patten PE, Calle Y, et al. Evidence for a macromolecular complex in poor prognosis CLL that contains CD38, CD49d, CD44 and MMP-9. Br J Haematol. 2011 Jul;154(2):216-222. doi: 10.1111\/j.1365-2141.2011.08725.x.","DOI":"10.1111\/j.1365-2141.2011.08725.x"},{"key":"ref7","doi-asserted-by":"crossref","unstructured":"8. Paulus A, Malavasi F, Chanan-Khan A. CD38 as a multifaceted immunotherapeutic target in CLL. Leuk Lymphoma. 2022 Oct;63(10):2265-2275. doi: 10.1080\/10428194.2022.2076849.","DOI":"10.1080\/10428194.2022.2090551"},{"key":"ref8","doi-asserted-by":"crossref","unstructured":"9. Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, D\u00f6hner H, et al. iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL. Blood. 2018 Jun; 131(25):2745-2760. doi: 10.1182\/blood-2017-09-806398.","DOI":"10.1182\/blood-2017-09-806398"},{"key":"ref9","doi-asserted-by":"crossref","unstructured":"10. Fadl HAO, Abdelmoneim AH, Elbager SG. Bio-informatic Analysis of Missense Single Nucleotide Polymorphisms (SNPs) in Human CD38 Gene Associated with B-Chronic Lymphocytic Leukemia. bioRxiv [Preprint]. 2020 Aug 17. doi: 10.1101\/2020.08.17.253906.","DOI":"10.1101\/2020.08.12.241976"},{"key":"ref10","doi-asserted-by":"crossref","unstructured":"11. Cerreto M, Fo\u00e0 R, Natoni A. The role of the microenvironment and cell adhesion molecules in chronic lymphocytic leukemia. Cancers (Basel). 2023 Oct 26;15(21):5160. doi: 10.3390\/cancers15215160.","DOI":"10.3390\/cancers15215160"},{"key":"ref11","doi-asserted-by":"crossref","unstructured":"12. Wu Z, Lu J, Loo A, Ho N, Nguyen D, Cheng PY, et al. Role of CD44 in chemotherapy treatment outcome: a scoping review of clinical studies. Int J Mol Sci. 2024 Mar 8;25(6):3141. doi: 10.3390\/ijms25063141.","DOI":"10.3390\/ijms25063141"},{"key":"ref12","doi-asserted-by":"crossref","unstructured":"13. Hassn Mesrati M, Syafruddin SE, Mohtar MA, Syahir A. CD44: a multifunctional mediator of cancer progression. Biomolecules. 2021 Dec 10;11(12):1850. doi: 10.3390\/biom11121850.","DOI":"10.3390\/biom11121850"},{"key":"ref13","unstructured":"14. Mirgayazova R, Khadiullina R, Gilyazova E, Davletshin D, Ganeeva I, Zmievskaya E, et al. The importance of TP53 status in cancer therapy: The example of chronic lymphocytic leukemia. Mol Biol Res Commun. 2025;14(3):179-188. doi: 10.22099\/mbrc.2024.51234.1950."},{"key":"ref14","doi-asserted-by":"crossref","unstructured":"15. Hendy OM, Mohamed AAE, Elsakhawy YN, Atta AS, Diab KAA. Evaluation of TP53 Gene Mutation in Chronic Lymphocytic Leukemia Patients. Egypt J Hosp Med. 2022 Oct; 89(1): 5807-5812. doi: 10.21608\/ejhm.2022.266205.","DOI":"10.21608\/ejhm.2022.266058"},{"key":"ref15","doi-asserted-by":"crossref","unstructured":"16. Bomben R, Rossi FM, Vit F, Bittolo T, D\u2019Agaro T, Zucchetto A, et al. TP53 mutations with low variant allele frequency predict short survival in chronic lymphocytic leukemia. Clin Cancer Res. 2021 Oct 15; 27(20): 5566-5575. doi: 10.1158\/1078-0432.CCR-21-0853.","DOI":"10.1158\/1078-0432.CCR-21-0701"},{"key":"ref16","doi-asserted-by":"crossref","unstructured":"17. Zhang X, Wang H, Zhang Y, Wang X. Advances in epigenetic alterations of chronic lymphocytic leukemia: from pathogenesis to treatment. Clin Exp Med. 2024 Mar 16;24. doi: 10.1007\/s10238-023-01268-x","DOI":"10.1007\/s10238-023-01268-x"},{"key":"ref17","doi-asserted-by":"crossref","unstructured":"18. Lazarian G, Guieze R, Wu CJ. Clinical Implications of Novel Genomic Discoveries in Chronic Lymphocytic Leukemia. J Clin Oncol. 2017 Mar 20; 35(9): 984-993. doi: 10.1200\/JCO.2016.71.0822.","DOI":"10.1200\/JCO.2016.71.0822"},{"key":"ref18","doi-asserted-by":"crossref","unstructured":"19. Shindiapina P, Brown JR, Danilov AV. A new hope: novel therapeutic approaches to treatment of chronic lymphocytic leukaemia with defects in TP53. Br J Haematol. 2014;167:149-61. doi: 10.1111\/BJH.13042.","DOI":"10.1111\/bjh.13042"}],"container-title":["Polski Merkuriusz Lekarski"],"original-title":[],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T19:09:56Z","timestamp":1777403396000},"score":1,"resource":{"primary":{"URL":"https:\/\/polskimerkuriuszlekarski.pl\/wp-content\/uploads\/library\/PolMerkurLek20026i2net.pdf"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,1]]},"references-count":19,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,4,1]]},"published-print":{"date-parts":[[2026,4,1]]}},"URL":"https:\/\/doi.org\/10.36740\/merkur202602101","relation":{},"ISSN":["1426-9686"],"issn-type":[{"value":"1426-9686","type":"print"}],"subject":[],"published":{"date-parts":[[2026,4,1]]}}}