Differential expression pattern of protein markers for predicting chemosensitivity of dexamethasone-based chemotherapy of B cell acute lymphoblastic leukemia

Abstract

Dexamethasone is considered as a direct chemotherapeutic agent in the treatment of pediatric acute lymphoblastic leukemia (ALL). Beside the advantages of the drug, some problems arising from the dose-related side effects are challenging issues during the treatment. Accordingly, the classification of patients to dexamethasone sensitive and resistance groups can help to select optimizing the therapeutic dose with the lowest adverse effects particularly in sensitive cases. For this purpose, we investigated inhibited proliferation and induced cytotoxicity in NALM-6 cells, as sensitive cells, after dexamethasone treatment. In addition, comparative protein expression analysis using the 2DE-MALDI-TOF MS technique was performed to identify the specific altered proteins. In addition, we evaluated mRNA expression levels of the identified proteins in bone-marrow samples from pediatric ALL patients using the real-time q-PCR method. Eventually, proteomic analysis revealed a combination of biomarkers, including capping proteins (CAPZA1 and CAPZB), chloride channel (CLIC1), purine nucleoside phosphorylase (PNP), and proteasome activator (PSME1), in response to the dexamethasone treatment. In addition, our results indicated low expression of identified proteins at both the mRNA and protein expression levels after drug treatment. Moreover, quantitative real-time PCR data analysis indicated that independent of the molecular subtypes of the leukemia, CAPZA1, CAPZB, CLIC1, and PNP expression levels were lower in ALL samples than normal samples, although PSME1 expression level was higher in ALL samples than normal samples. Furthermore, the expression level of all proteins (except PSME1) was different between high-risk and standard-risk patients that suggesting the prognostic value of them. In conclusion, our study suggests a panel of biomarkers comprising CAPZA1, CAPZB, CLIC1, PNP, and PSME1 as early diagnosis and treatment evaluation markers that may differentiate cancer cells which are presumably to benefit from dexamethasone-based chemotherapy and may facilitate the prediction of clinical outcome.

Intracellular Chloride Channels: Novel Biomarkers in Diseases

“…Along with CLIC4, CLIC1 is a promising biomarker for epithelial ovarian cancer where its expression predicts patient survival (Singha et al, 2018). CLIC1 is shown to regulate the redox-sensitivity of ovarian cancer cells and is predicted to be a potential marker for lymphoblastic leukemia (Qu et al, 2016;Dehghan-Nayeri et al, 2017;Singha et al, 2018). Modulation of CLIC1 expression by micro RNA, hsa-mir-372 predicts the poor prognosis of patients affected with gall bladder cancers (Zhou et al, 2017) and is important for the migration and invasion of gall bladder cancer cells (He et al, 2018).…”

Methanolic Extract from Aerial Parts of Artemisia Annua L. Induces Cytotoxicity and Enhances Vincristine-Induced Anticancer Effect in Pre-B Acute Lymphoblastic Leukemia Cells

“…Acute lymphoblastic leukemia (ALL) affects both children and adults with a peak occurrence at 2 to 5 years of age 1 , 2 , 3 . Despite substantial improvements in treatment of ALL patients, the relapse rate is still considered as a major challenge in these people 4 , 5 .…”

CAPZA1 determines the risk of gastric carcinogenesis by inhibitingHelicobacter pyloriCagA-degraded autophagy

“…Real-time polymerase chain reaction (PCR) was performed using a SYBR Premix Ex Taq Perfect Real Time Kit (TaKaRa, RR041A) in a Thermal Cycler Dice Real Time System (TaKaRa, Ohtsu, Japan). The primer sequences used were as follows: LAMP1 mRNA: forward 5ʹ-CCAGTTCGGGATGAATGCAAGT and reverse 5ʹ-TTGGCAGCTTTAAAGGCAGGGT [49]; CAPZA1 mRNA: forward 5ʹ-ACAATCTCCTCAGGGAAGGGG and reverse 5ʹ-TGCTTCTTTCCGTAAGTGGTCAAA [50]; GAPDH mRNA: forward 5ʹ-GACATCAAGAAGGTGGTGAAGCAG and reverse 5ʹ-ATACCAGGAAATGAGCTTGACAAA [8]. The cells' GAPDH gene were used as the internal control for the quantitative RT-PCR.…”