학술논문
Prognostic Relevance of Expression of EMP1 , CASP1 , and NLRP3 Genes in Pediatric B-Lineage Acute Lymphoblastic Leukemia.
Document Type
Academic Journal
Author
Singh J; Laboratory Oncology Unit, Dr. B.R. Ambedkar-Insitute Rotary Cancer Hospital (BRAIRCH), All India Institute of Medical Sciences (AIIMS), New Delhi, India.; Kumari S; Laboratory Oncology Unit, Dr. B.R. Ambedkar-Insitute Rotary Cancer Hospital (BRAIRCH), All India Institute of Medical Sciences (AIIMS), New Delhi, India.; Arora M; Department of Biochemistry, AIIMS, New Delhi, India.; Verma D; Laboratory Oncology Unit, Dr. B.R. Ambedkar-Insitute Rotary Cancer Hospital (BRAIRCH), All India Institute of Medical Sciences (AIIMS), New Delhi, India.; Palanichamy JK; Department of Biochemistry, AIIMS, New Delhi, India.; Kumar R; Department of Pathology, Mahavir Cancer Sansthan, Patna, India.; Sharma G; Department of Biochemistry, AIIMS, New Delhi, India.; Bakhshi S; Department of Medical Oncology, AIIMS, New Delhi, India.; Pushpam D; Department of Medical Oncology, AIIMS, New Delhi, India.; Ali MS; Department of Pulmonary Medicine, AIIMS, New Delhi, India.; Ranjan A; Laboratory Oncology Unit, Dr. B.R. Ambedkar-Insitute Rotary Cancer Hospital (BRAIRCH), All India Institute of Medical Sciences (AIIMS), New Delhi, India.; Tanwar P; Laboratory Oncology Unit, Dr. B.R. Ambedkar-Insitute Rotary Cancer Hospital (BRAIRCH), All India Institute of Medical Sciences (AIIMS), New Delhi, India.; Chauhan SS; Department of Biochemistry, AIIMS, New Delhi, India.; Singh A; Department of Biochemistry, AIIMS, New Delhi, India.; Chopra A; Laboratory Oncology Unit, Dr. B.R. Ambedkar-Insitute Rotary Cancer Hospital (BRAIRCH), All India Institute of Medical Sciences (AIIMS), New Delhi, India.
Source
Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101568867 Publication Model: eCollection Cited Medium: Print ISSN: 2234-943X (Print) Linking ISSN: 2234943X NLM ISO Abbreviation: Front Oncol Subsets: PubMed not MEDLINE
Subject
Language
English
ISSN
2234-943X
Abstract
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.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2021 Singh, Kumari, Arora, Verma, Palanichamy, Kumar, Sharma, Bakhshi, Pushpam, Ali, Ranjan, Tanwar, Chauhan, Singh and Chopra.)
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2021 Singh, Kumari, Arora, Verma, Palanichamy, Kumar, Sharma, Bakhshi, Pushpam, Ali, Ranjan, Tanwar, Chauhan, Singh and Chopra.)