<i>Cyclin dependent kinase inhibitor 2A/B</i> gene deletions are markers of poor prognosis in Indian children with acute lymphoblastic leukemia

Agarwal, Manisha; Bakhshi, Sameer; Dwivedi, Sadanand; Kabra, Madhulika; Shukla, Rashmi; Seth, Rachna

doi:10.1002/pbc.27001

Cited by 24 publications

(32 citation statements)

References 27 publications

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“…CDKN2B is a cyclin‐dependent kinase inhibitor which makes complex with CDK4 or CDK6 and interferes with the activation of cyclin‐dependent kinases . Importantly, expression of CDKN2B was shown to be diminished or lost in multiple types of human cancers, suggesting its significant tumour suppressor role . Taken together our findings suggest that both dichloromethane and hexane extracts of saffron target the expression of tumour suppressor CDKN2B gene in osteosarcoma cells to show antitumour effects.…”

Section: Discussioncontrasting

confidence: 99%

“…[23] Importantly, expression of CDKN2B was shown to be diminished or lost in multiple types of human cancers, suggesting its significant tumour suppressor role. [23,24] Taken together our findings suggest that both dichloromethane and hexane extracts of saffron target the expression of tumour suppressor CDKN2B gene in osteosarcoma cells to show antitumour effects. Additionally, we also established the DNA laddering which is a significant event used for the analysis of cells undergoing apoptosis.…”

Section: Discussionmentioning

confidence: 59%

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Pharmacological properties and therapeutic potential of saffron (Crocus sativus L.) in osteosarcoma

Eğe

Yumrutaş

Ege

et al. 2019

Journal of Pharmacy and Pharmacology

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Objectives In this comprehensive study, we aimed to investigate pharmacological properties and therapeutic significance of saffron in osteosarcoma cancer cells. Methods Plant materials were obtained from Safranbolu district of Karabuk, Turkey. For the determination of anticancer properties, thiazolyl blue tetrazolium bromide (MTT) cell viability, colony formation, wound closure, DNA ladder assays and gene expression analysis by real‐time PCR were performed. Also, cellular inflammation, total antioxidant and oxidants status were determined. Key findings Dichloromethane and hexane extracts of saffron were significantly inhibited cell proliferation and interfered with colony forming and migration capabilities of U2‐OS osteosarcoma cancer cells. Also, both extracts induced the activation of tumour suppressor CDKN2B gene and altered cellular morphology resembling the induction of apoptosis. However, DNA fragmentation was not observed after extract treatments. Saffron was also found to have no significant effect on cellular inflammation. Unexpectedly, both dichloromethane and hexane extracts of saffron had no marked effect on cellular total antioxidant and oxidant status. Lastly, vanillic acid, resveratrol, caffeic acid and 4‐hydroxybenzoic acid were found to be highly rich in our extracts. Conclusions Findings of this study demonstrated significant antiproliferative and antitumorigenic properties of saffron in osteosarcoma.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 59%

Pharmacological properties and therapeutic potential of saffron (Crocus sativus L.) in osteosarcoma

Eğe

Yumrutaş

Ege

et al. 2019

Journal of Pharmacy and Pharmacology

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“…Tumor suppressor genes CDKN2A and CDKN2B at 9p21, which encode p14/ARF and p16/INK4A (both encoded by CDKN2A) and p15/INK4B (encoded by CDKN2B) proteins have a role in cell growth regulation and apoptosis. Thus, here observed homozygous deletion represents a marker of high risk of relapse and poor prognosis in children B-ALL as reported in previous studies (26)(27)(28).…”

Section: Discussionsupporting

confidence: 88%

Complex karyotype with cryptic FUS gene rearrangement and deletion of NR3C1 and VPREB1 genes in childhood B‑cell acute lymphoblastic leukemia: A case report

et al. 2020

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B-cell acute lymphoblastic leukemia (B-ALL) is a hematopoietic malignancy characterized by overproduction of immature B-lymphoblasts. BALL is the most common pediatric tumor and remains the leading cause of mortality in children and adolescents. Molecular and cytogenetic analyses of BALL revealed recurrent genetic and structural genomic alterations which are routinely applied for diagnosis, prognosis and choice of treatment regimen. The present case report describes a 4-year-old female diagnosed with BALL. GTG-banding at low resolution revealed an abnormal clone with 46,XX,?t(X;19)(q13;q13.3),der(9) besides normal cells. Molecular cytogenetics demonstrated a balanced translocation between chromosomes 16 and 19, and an unbalanced translocation involving chromosomes 5 and 9. A locus-specific probe additionally identified that the FUS gene in 16p11.2 was split and its 5' region was translocated to subband 19q13.33, whereas the 3' region of the FUS gene remained on the derivative chromosome 16. Overall, this complex karyotype included four different chromosomes and five break events. Further analyses, including array-comparative genomic hybridization, additionally revealed biallelic deletion of the tumor suppressor genes CDKN2A/B, and deletion of the NR3C1 and VPREB1 genes. The patient passed away under treatment due to sepsis.

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“…The literature screening process is shown as a flow diagram in Figure 1. Finally, 13 studies with a total number of 2857 patients were included in this metaanalysis [14][15][16][17][18][21][22][23][24][25][26][27][28]. These studies were published between 2005 and 2018 and the sample size ranged from 54 to 864 with a median of 81.…”

Section: Study Selection and Characteristicsmentioning

confidence: 99%

Prognostic significance of CDKN2A/B deletions in acute lymphoblastic leukaemia: a meta-analysis

2019

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Background: Cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) genes are frequently altered in acute lymphoblastic leukaemia (ALL) patients. The aim of this meta-analysis was to comprehensively assess the prognostic value of CDKN2A/B deletions in ALL patients. Methods: Systematic literature review was conducted in PubMed, Embase and Cochrane databases up to July 2018. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated with fixed-effects or random-effects models. Results: A total of thirteen studies including 2857 patients were eligible for this meta-analysis. Combined HRs suggested that CDKN2A/B deletions were poor prognostic factors for both overall survival (OS) (HR ¼ 2.15, 95% CI 1.82-2.54) and event-free survival (EFS)/disease-free survival (DFS)/relapse-free survival (RFS) (HR ¼ 2.16, 95% CI 1.73-2.69). The adverse impact remained significant in both adult and paediatric ALL patients, and also in subgroups by ethnicity, ALL type, detection method of CDKN2A/B deletions, statistical method and endpoint. Conclusions: Our findings suggested that CDKN2A/B deletions were associated with poor prognosis independently in both adult and childhood ALL patients. Inclusion of CDKN2A/B status may further improve the risk stratification of ALL patients. KEY MESSAGESAlthough numerous studies have explored the prognostic significance of cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) deletions in acute lymphoblastic leukaemia (ALL) patients, the results remain conflicting. In this meta-analysis, we found that CDKN2A/B deletions were independent poor prognostic markers for both adult and paediatric ALL patients. Our findings justify the inclusion of CDKN2A/B status in the risk stratification of ALL patients.

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Cyclin dependent kinase inhibitor 2A/B gene deletions are markers of poor prognosis in Indian children with acute lymphoblastic leukemia

Abstract: CDKN2A/B deletions were significantly more prevalent in T-ALL subgroup and were found to have higher hazard ratio and lesser event free survival in total cohort in our study.

Cited by 24 publications

References 27 publications

Pharmacological properties and therapeutic potential of saffron (Crocus sativus L.) in osteosarcoma

Pharmacological properties and therapeutic potential of saffron (Crocus sativus L.) in osteosarcoma

Complex karyotype with cryptic FUS gene rearrangement and deletion of NR3C1 and VPREB1 genes in childhood B‑cell acute lymphoblastic leukemia: A case report

Prognostic significance of CDKN2A/B deletions in acute lymphoblastic leukaemia: a meta-analysis

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