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Complement plays a dual regulatory role in carcinogenesis, affecting the immune response outcomes. Membrane-bound complement regulators (mCRPs) include CD59 and CD35; where CD59 inhibits MAC formation and CD35 binds C3b\/C4b for immune clearance. The current study aims to assess post-transcriptional expression levels of complement regulatory proteins CD35 and CD59 in acute leukemia patients. CD35 expression was significantly downregulated in acute leukemia in comparison to their normal counterparts at both transcriptional and protein levels (5.3-and 4-folds respectively), conversely CD59 expression was significantly increased (3 and 1.3 folds respectively). An HSB-2 acute leukemia cell model was established, and post-transcriptional silencing of CD35 and CD59 using shRNA was performed. MTT viability assays showed increased viability following CD35 silencing; conversely CD59 silencing caused a significant decrease in cell viability. The results suggest an altered pattern of mCRP expression on leukemic cells; where CD35 was downregulated, possibly to benefit from the complement system activation products in promoting carcinogenesis. Alternatively, leukemic cells might overexpress CD59 to enhance cell survival and escape MAC induced lysis. Our results suggest that abnormally altered expression of complement regulatory proteins (CRPs) could be\u00a0a key mechanism employed by leukemic cells to evade destruction by the host's complement system to promote tumor progression, and indicate their potential implication as differentiation markers in acute leukemias.<\/jats:p>","DOI":"10.1007\/s12672-026-04818-3","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T14:25:01Z","timestamp":1775139901000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Altered expression of complement regulatory proteins CD35 and CD59 in acute lymphoblastic and acute myeloblastic leukemia suggests a context-based pattern"],"prefix":"10.1007","volume":"17","author":[{"given":"Reem Hossam EL-Din","family":"Ahmed","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menatalla Mostafa","family":"Mahmoud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed Ahmed","family":"El-Azizi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noha Samir","family":"Farag","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,2]]},"reference":[{"key":"4818_CR1","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1038\/cr.2009.139","volume":"20","author":"JR Dunkelberger","year":"2010","unstructured":"Dunkelberger JR, Song WC. 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Informed consent was provided to the patients by the National Cancer Institute, Cairo. \u201cI have read (or had read to me) the information above. I have had the opportunity to ask questions and have received satisfactory answers. I voluntarily agree to participate in this study and to provide a blood sample for research purposes\u201d.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"552"}}