Iron protects childhood acute lymphoblastic leukemia cells from methotrexate cytotoxicity

Iron a tiny molecule with huge effects. Our findings showed that iron participates in drug resistance and iron ‐overload can be considered as a risk factor for relapse. In an attempt to minimize the probability of drug resistance and improve the treatment outcomes in children with ALL, it is suggested that patients' bone marrow iron stores must be assessed during chemotherapy, and the number of blood trans fusions should be carefully monitored. AbstractDrug resistance is a fundamental clinical concern in pediatric acute lymphoblastic leukemia (pALL), and methotrexate (MTX) is an essential chemotherapy drug administered for the treatment. In the current study, the effect of iron in response to methotrexate and its underlying mechanisms were investigated in pALL cells. CCRF ‐CEM and Nalm6 cell lines were selected as T and B‐ALL subtypes. Cells were pretreated with ferric ammonium citrate, exposed to the IC50 concentration of MTX and cell viability was assessed using MTT, colony formation, and flow cytometry assays. Iron‐loaded cells were strongly resistant to MTX cytotoxicity. The inhibitory effect of N‐acetyl cysteine to reverse the acquired MTX resistance was greater than that of the iron chelator, deferasirox, highlighting the importance of iron‐mediated ROS in MTX resistance. Subsequently, the upregulation ofBCL2,SOD2,NRF2, andMRP1 was confirmed using quantitative RT ‐PCR. Moreover, a positive correlation was demonstrated between theMRP1 expression levels and ...
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research