Expression analysis of <i><scp>BECN</scp>1</i> in acute myeloid leukemia: association with distinct cytogenetic and molecular abnormalities

Zare‐Abdollahi, Davood; Safari, Shamsi; Movafagh, Abolfazl; Ghadiani, Mohammad Hassan; Tabarraee, Mehdi; Riazi-Isfahani, Sahand; Gorji, Shahabeddin; Keyvan, L.; Gachkar, Latif

doi:10.1111/ijlh.12454

Cited by 10 publications

(11 citation statements)

References 24 publications

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“…In AML patients, reduced BECN1 gene expression was associated with older age and higher TLC. Our values were very close to the findings of Zare-Abdollahi et al [17], who reported a mean age of 52.9 years and a mean TLC of 52.6 × 10 3 /μl in AML patients with reduced BECN1 gene expression. However, we did not observe a significant relationship between the level of BECN1 gene expression and sex, haemoglobin level, or platelet count.…”

Section: Discussionsupporting

confidence: 91%

“…Upon detailed analysis, we found that 72.0% of the patients had reduced BECN1 gene expression compared to the control group and that 28.0% of the patients had normal BECN1 gene expression. This result is in accordance with Zare-Abdollahi et al [17], who analysed the expression status of the BECN1 gene in a series of 128 de novo AML patients using real-time quantitative polymerase chain reaction, in which BECN1 reduced expression was detected in 57 of the 128 cases (45%). In another study performed by Mohamadimaram et al [18], expression of other autophagy genes (namely, ATG7 and light chain 3 (LC3)) was investigated, and the authors found a significant decrease in expression levels of both genes in most AML patients (81.81% and 75.55%, respectively).…”

Section: Discussionsupporting

confidence: 90%

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Reductive regulation of BECN1 gene in adult Egyptian patients with do novo AML

Ghozlan

Farweez

Safwat

et al. 2020

Egypt J Med Hum Genet

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Background Acute myeloid leukaemia (AML) is a clonal haematopoietic disease characterized by the proliferation of immature blast cells in the bone marrow and peripheral blood. Autophagy is an inherent cellular route by which waste macromolecules are engulfed within autophagosomes prior to their fusion with cytoplasmic lysosomes for degradation. The BECN1 gene encodes the Beclin-1 protein, which regulates autophagy. Few reports have investigated BECN1 gene expression and its value in AML patients. Results This randomized case-control study included 50 newly diagnosed AML patients, in addition to 20 subjects as a control group. BECN1 gene expression was assessed using real-time quantitative polymerase chain reaction (qRT-PCR). The median level of BECN1 gene expression in AML patients was 0.41 (IQR 0.29–1.03) in comparison to 1.12 (IQR 0.93–1.26) in the control group (P = 0.000). Seventy-two percent of AML patients showed reduced BECN1 gene expression, which was highly significantly associated with intermediate and adverse cytogenetic risk. Reduced BECN1 gene expression was associated with older age, higher total leukocyte counts, the presence of peripheral blood blast cells, a higher percentage of bone marrow blast cells, and higher expression of CD34 and CD117. FLT3-ITD mutation was detected in 14 patients (38.9%), all of whom showed reduced BECN1 gene expression (P = 0.006). BECN1 gene expression was also reduced in non-responder AML patients, with a highly statistically significant difference (P = 0.002). Conclusion A reduction in BECN1 gene expression might indicate a poor prognosis in adult Egyptian patients with de novo AML. Decreased BECN1 gene expression is associated with a higher risk of resistance to treatment. Targeting autophagy pathways may help in the treatment of AML patients.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 90%

Reductive regulation of BECN1 gene in adult Egyptian patients with do novo AML

Ghozlan

Farweez

Safwat

et al. 2020

Egypt J Med Hum Genet

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“…Two previous studies have described an association between low expression at the mRNA level of single autophagic regulators and an adverse prognosis. First, BECN1 is important for the initiation and advance of autophagy, and reduced BECN1 mRNA levels were associated with an adverse prognosis, FLT3-ITD, monosomal karyotype and high age [88]. Second, decreased BECN1 mRNA expression is also associated with an adverse prognosis [89].…”

Section: Discussionmentioning

confidence: 99%

Proteome and Phosphoproteome Changes Associated with Prognosis in Acute Myeloid Leukemia

Aasebø

Berven

Bartaula-Brevik

et al. 2020

Cancers

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Acute myeloid leukemia (AML) is a hematological cancer that mainly affects the elderly. Although complete remission (CR) is achieved for the majority of the patients after induction and consolidation therapies, nearly two-thirds relapse within a short interval. Understanding biological factors that determine relapse has become of major clinical interest in AML. We utilized liquid chromatography tandem mass spectrometry (LC-MS/MS) to identify the protein changes and protein phosphorylation events associated with AML relapse in primary cells from 41 AML patients at time of diagnosis. Patients were defined as relapse-free if they had not relapsed within a five-year clinical follow-up after AML diagnosis. Relapse was associated with increased expression of RNA processing proteins and decreased expression of V-ATPase proteins. We also observed an increase in phosphorylation events catalyzed by cyclin-dependent kinases (CDKs) and casein kinase 2 (CSK2). The biological relevance of the proteome findings was supported by cell proliferation assays using inhibitors of V-ATPase (bafilomycin), CSK2 (CX-4945), CDK4/6 (abemaciclib) and CDK2/7/9 (SNS-032). While bafilomycin preferentially inhibited the cells from relapse patients, the kinase inhibitors were less efficient in these cells. This suggests that therapy against the upregulated kinases could also target the factors inducing their upregulation rather than their activity. This study, therefore, presents markers that could help predict AML relapse and direct therapeutic strategies.

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“…Beclin 1 and LC3 are reportedly down-regulated in AML cells compared to normal cells [26]: with Zare-Abdollahi et al [8] verifying that Beclin 1 down-regulation is associated with the FLT3-ITD fusion in AML patients. In addition, low ULK1-expression patients had higher WBC counts than the high ULK1 group.…”

Section: Clinical Characteristics Of Aml Patientsmentioning

confidence: 83%

Expression of autophagy genes in acute myeloid leukemia: associations with clinical characteristics and prognosis

Peng

Miao

Liu

et al. 2018

neo

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The relationships between autophagy-associated gene expression and clinical characteristics and prognosis in acute myeloid leukemia (AML) have not been well revealed. We examined mRNA expression of Bcl-2, p62, Beclin 1, VPS34, Rubicon, ALFY, UVRAG, ULK1, LC3 and NBR1 in 20 AML cases and 10 benign hematological cases by real-time PCR. Clinical information, treatment responses and outcomes of the AML patients were collected. Beclin 1, LC3, UVRAG, Rubicon and NBR1 were downregulated in AML patients compared with control group (P<0.05). Low ULK1 expression was associated with high white blood cell counts (P<0.05). Autophagy-associated gene expression was not correlated with chemotherapy response. Finally, we analyzed overall survival and found no obvious association with gene expression. However, in unfavorable outcome patients, low Beclin 1 and p62 expression showed worse overall survival than high-expression. Autophagy genes are associated with outcome in AML patients and may be biomarkers or targets in the future.

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Expression analysis of BECN1 in acute myeloid leukemia: association with distinct cytogenetic and molecular abnormalities

Abstract: Overall, remarkable association of reduced expression of BECN1 with FLT3-ITD mutation and monosomal karyotype and their functional relationship is interesting which should be addressed and verified in future studies.

Cited by 10 publications

References 24 publications

Reductive regulation of BECN1 gene in adult Egyptian patients with do novo AML

Reductive regulation of BECN1 gene in adult Egyptian patients with do novo AML

Proteome and Phosphoproteome Changes Associated with Prognosis in Acute Myeloid Leukemia

Expression of autophagy genes in acute myeloid leukemia: associations with clinical characteristics and prognosis

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