Correlation of Day 8 Steroid Response with Bone Marrow Status Measured on Days 14 and 35, in Patients with Acute Lymphoblastic Leukemia Being Treated with BFM Protocol

Kamat, Girish; Subramanian, Kannan; Apte, Shashikant

doi:10.1007/s12288-019-01119-4

Cited by 1 publication

(2 citation statements)

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“…This might be due to the complexity of the disease mechanism, which may get modulated during the treatment. Interestingly, during induction therapy with prednisolone, day 14 blast count status, but not day 35 blast count status is correlated with day 8 blast count in BFM protocol (45). In the study by Paugh et al (2015), mRNA of CASP1 and NLRP3 were overexpressed at 1.6 fold and 2.4 fold, respectively, in GC-resistant ALL cells compared to GC-sensitive ALL cells (15,46).…”

Section: Discussionmentioning

confidence: 96%

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Prognostic Relevance of Expression of EMP1, CASP1, and NLRP3 Genes in Pediatric B-Lineage Acute Lymphoblastic Leukemia

et al. 2021

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Glucocorticoid (GC), such as prednisolone, is an essential component of multidrug chemotherapy regimen for pediatric acute lymphoblastic leukemia (ALL). Resistance to GC in leukemia cells is associated with disease progression and poor prognosis. Despite the extensive use of GC for many years, molecular mechanisms underlying its resistance in ALL have not been fully uncovered. Recent studies have shown a potential role of EMP1, CASP1, and NLRP3 genes in prednisolone response. In this study on 148 pediatric B-ALL patients, we studied these three genes to assess their association with prednisolone response measured by day 8 blast count after 7 days of induction therapy with prednisolone. Intriguingly, ALL samples exhibited higher expression of EMP1 along with a low expression of CASP1 and NLRP3 compared to disease free normal bone marrow collected from patients with solid tumors. Among the three analyzed genes, only EMP1 was found to be overexpressed in prednisolone poor responders (p=0.015). Further, a comparison of gene expression between cytogenetic subtypes revealed higher expression of EMP1 in BCR-ABL subtype. Expression of EMP1 in multiple gene expression datasets was used for gene set enrichment analysis, which revealed TNF-α, IL-2-STAT5 signaling, inflammatory responses and hypoxia as the major positively associated pathways and E2F targets as negatively associated pathways. Interestingly, the clinical remission rate was higher in CASP1 high patients (p=0.048). In univariate survival analysis, higher EMP1 expression was associated with poor prognostic measures while higher expression of NLRP3 and CASP1 was associated with better prognostic measures in our data. Further, multivariate analysis revealed an independent association of high CASP1 and NLRP3 with a better prognosis. This study strengthens the available evidence that mRNA expression of EMP1, CASP1, and NLRP3 may serve as potential biomarkers for risk stratification of pediatric B-ALL patients.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%