Iranian journal of pathology · 2025
Expression of ADAM10 and CD58 in Acute and Chronic Lymphocytic Leukemia: Influence of Disease Stage and Chemotherapy.
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Kadhim Ameer Hamid, Mohsin Muslim Idan
Аннотация
BACKGROUND & OBJECTIVE: CD58 and ADAM10 have been implicated in leukemia progression and chemoresistance; however, their specific roles in acute lymphoblastic leukemia (ALL) and chronic lymphocytic leukemia (CLL), particularly under chemotherapeutic pressure, remain insufficiently characterized. This study aimed to assess the expression of CD58, an immune adhesion molecule, and ADAM10, a metalloproteinase, in ALL and CLL patients undergoing chemotherapy, and to explore their potential involvement in immune evasion, niche-mediated survival, and chemoresistance mechanisms.
METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from 50 patients with ALL, 50 with CLL, and 30 healthy controls. Expression levels of CD58 and ADAM10 were analyzed by quantitative reverse transcription PCR (qRT-PCR) and flow cytometry. Chemotherapy regimens included vincristine (VCR), methotrexate (MTX), and doxorubicin (DOXO).
RESULTS: ADAM10 mRNA expression was significantly upregulated in ALL patients treated with VCR+MTX (p<0.0001) and DOXO (p=0.001), with corresponding protein overexpression observed in both ALL (p<0.0001) and untreated CLL patients (p<0.0001). A significant difference in ADAM10 levels was noted between ALL and CLL cohorts (p=0.001). CD58 mRNA and protein expression were markedly increased in ALL patients receiving VCR+MTX (p<0.0001), whereas untreated CLL patients exhibited no significant alterations.
CONCLUSION: CD58 and ADAM10 are differentially regulated in ALL under chemotherapy, supporting their roles in immune evasion and microenvironmental survival. The constitutive overexpression of ADAM10 in CLL suggests its involvement in chronic leukemic pathogenesis. These findings highlight CD58 and ADAM10 as potential therapeutic targets for overcoming chemoresistance in lymphoid malignancies.
METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from 50 patients with ALL, 50 with CLL, and 30 healthy controls. Expression levels of CD58 and ADAM10 were analyzed by quantitative reverse transcription PCR (qRT-PCR) and flow cytometry. Chemotherapy regimens included vincristine (VCR), methotrexate (MTX), and doxorubicin (DOXO).
RESULTS: ADAM10 mRNA expression was significantly upregulated in ALL patients treated with VCR+MTX (p<0.0001) and DOXO (p=0.001), with corresponding protein overexpression observed in both ALL (p<0.0001) and untreated CLL patients (p<0.0001). A significant difference in ADAM10 levels was noted between ALL and CLL cohorts (p=0.001). CD58 mRNA and protein expression were markedly increased in ALL patients receiving VCR+MTX (p<0.0001), whereas untreated CLL patients exhibited no significant alterations.
CONCLUSION: CD58 and ADAM10 are differentially regulated in ALL under chemotherapy, supporting their roles in immune evasion and microenvironmental survival. The constitutive overexpression of ADAM10 in CLL suggests its involvement in chronic leukemic pathogenesis. These findings highlight CD58 and ADAM10 as potential therapeutic targets for overcoming chemoresistance in lymphoid malignancies.