Expression and clinical significance of SNAI1 and ZEB1 genes in acute myeloid leukemia patients

Shousha, Wafaa Gh.; Ramadan, Shimaa Shawki; El-Saiid, Abeer Salah; Abdelmoneim, Ahmed Essmat; Abbas, Marwa Ahmed

doi:10.1007/s11033-019-04839-y

Cited by 11 publications

(9 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…SNAI1 is overexpressed in many cancers and is associated with poor outcomes 7 . Recently, after the start of our study, two papers showed that SNAI1 is overexpressed in the bone marrow and peripheral blood samples of AML patients 8,18 . However, to our knowledge, the present study is the first one to investigate SNAI1 expression levels in bone marrow samples of pediatric and on a larger sample size of adult de novo AML patients.…”

Section: Discussionmentioning

confidence: 76%

“…7 Recently, after the start of our study, two papers showed that SNAI1 is overexpressed in the bone marrow and peripheral blood samples of AML patients. 8,18 However, to our knowledge, the present study is the first one to investigate SNAI1 expression levels in bone marrow samples of pediatric and on a larger sample size of adult de novo AML patients. Also, the association between upregulated BM SNAI1 expression, the absence of HLA-DR antigen and drug resistance among treatment groups of adult and pediatric AML cohorts.…”

Section: Discussionmentioning

confidence: 91%

See 1 more Smart Citation

Bone marrow overexpression of SNAI1 is an early indicator of intrinsic drug resistance in patients with de novo acute myeloid leukemia

Gouda

Hassan

Kandil

2023

The Journal of Gene Medicine

View full text Add to dashboard Cite

Background: The lack of effectiveness of acute myeloid leukemia (AML) treatment remains a major challenge and resembles a principal cause of AML-related mortality owing to chemotherapy resistance. SNAI1 has been proved to be a leading factor in drug resistance in many cancer types. However, its relation to chemoresistance in AML is not well understood.Methods: In addition to standard lab work, the expression level of SNAI1 was determined in bone marrow samples of 109 adult and pediatric patients with de novo acute myeloid leukemia using RT-qPCR. The relation between SNAI1 and AML drug resistance and immunomodulatory genes was investigated using the STRING tool.Results: The SNAI1 expression level was upregulated in AML patients in particular samples with promyelocytic leukemia subtype against control cases. In the treatment response, SNAI1 was significantly higher in resistant patients in comparison with the complete remission group. SNAI1 overexpression was associated with high initial blasts and total leukocyte counts, but with HLA class II histocompatibility antigen DR downregulation. STRING analysis showed that multiple drug resistance and immunomodulatory genes of AML induce SNAI upregulation and activation. Kaplan-Meier analysis indicated that there was no relation between SNAI1 expression level and patient survival status. Conclusion:We conclude that the SNAI1 expression level may be a predictor of intrinsic drug resistance incidence in AML patients.acute myeloid leukemia (AML), drug resistance, HLA class II histocompatibility antigen DR (HLA-DR), immune suppression, promyelocytic leukemia (APL, AML-M3), retinoic acid receptor alpha (RAR-α), zinc finger protein SNAI1 | INTRODUCTIONAcute myeloid leukemia (AML) is a very heterogeneous malignant disease that exhibits uncontrolled clonal expansion of immature myeloid cells and ends in failure of normal hematopoiesis. 1 Leukemogenesis is thought to principally result from the accumulation of many genomic translocations and genetic mutations in hematopoietic stem cells during aging. 2 The AML incidence rate is considered to be three to five cases per 100,000 population and 68 years is the median age of diagnosis. The AML incidence rate does not change regarding race and ethnicity, but it is more common in men than women. Despite the advances in understanding the molecular mechanisms of AML development and in therapies that target it, standard AML induction regimens have remained unchanged for decades. A few years ago, new

show abstract

Section: Discussionmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 91%

Bone marrow overexpression of SNAI1 is an early indicator of intrinsic drug resistance in patients with de novo acute myeloid leukemia

Gouda

Hassan

Kandil

2023

The Journal of Gene Medicine

View full text Add to dashboard Cite

show abstract

“…For example, up-regulating ZEB1 improves the migration ability of HCC cells (Wang et al, 2020). ZEB1 is highly expressed in AML patients and can be a marker for early diagnosis and prognosis of AML (Shousha et al, 2019). However, ZEB1 knockout reduces the invasiveness of leukemia stem cells (Stavropoulou et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

MALAT-1 regulates the AML progression by promoting the m6A modification of ZEB1

Jin

Pan

et al. 2023

Acta Biochim Pol

View full text Add to dashboard Cite

Metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1) is abnormally upregulated in various human cancers. However, the role of MALAT-1 in acute myeloid leukemia (AML) remains unclear. This study investigated the expression and function of MALAT-1 in AML. MTT assay was used to determine cell viability, qRT-PCR was applied to determine the RNA levels. Western blot was performed to detect the protein expression. Flow cytometry was conducted to measure cell apoptosis. RNA pull-down assay was carried out to detect the interaction between MALAT-1 and METTL14. RNA FISH assay was performed to determine the localization of MALAT-1 and METTL14 in AML cells. Our results have revealed the key role of MEEL14 and m6A modification in AML. Besides, MALAT-1 was significantly up-regulated in AML patients. MALAT-1 knockdown inhibited the proliferation, migration and invasion of AML cells, and induced cell apoptosis; additionally, MALAT-1 binding to METTL14 promoted the m6A modification of ZEB1. Besides, ZEB1 overexpression partially reversed the effect of MALAT-1 knockdown on the cellular functions of AML cells. Taken together, MALAT-1 promoted the aggressiveness of AML through regulating m6A modification of ZEB1.

show abstract

“…Other signi cant examples of the fb-PMT-induced GES of pathway's interference include SNAI MYC HIF1A, TWIST1, and TFAP2C. Notably, inference of potential contribution to the fb-PMT anticancer activity of the interference with these pathways seems highly congruent with their known biological functions such as cell cycle control (MYC), survival and maintenance of stem cells (HIF1A, TFAP2C), and essential features of the malignant phenotype (TWIST1, SNAI) [38][39][40][41][42][43][44][45][46][47][48][49][50][51][52].…”

Section: Discussionmentioning

confidence: 99%

A Novel Fluorobenzyl Polyethylene Glycol Conjucated Tetraiodothyroacetic Acid (fb-PMT), Targeting Thyrointegrin αvβ3 in Treatment Acute Myeloid Leukemia

Darwish

Glinsky

Sudha

et al. 2021

Preprint

View full text Add to dashboard Cite

Background: Acute myeloid leukemia (AML) is associated with poor long-term survival, even with newer therapeutic agents. Here we show the results of our pre-clinical study, in which we evaluate the efficacy of a new thyrointegrin αvβ3 antagonist, named fluorobenzyl Polyethylene glycol conjucated tetraiodothyroacetic acid (fb-PMT).Methods and Results: fb-PMT effectively suppresses the malignant growth of human acute myeloid leukemia (AML) after successful engraftment in transgenic NSG-S xenograft mouse models of either established human AML cell line or primary AML cells. Daily treatment with fb-PMT (1-10 mg/kg body weight) subcutaneously (s.c.) for 3-4 weeks was associated with marked regression of leukemogenesis and extended survival in both models. The efficiency of the fb-PMT therapy was verified using IVIS imaging, flowcytometry and histopathological examination to monitor the engraftment of leukemic cells in the bone marrow and other organs. fb-PMT therapy for 3-4 weeks at 3 and 10 mg/kg daily doses exhibited significant reduction (P<0.0001) of leukemic cell burden of 74% and >95%, respectively. All fb-PMT-treated mice in the 10 mg/kg treatment arm successfully maintained remission after discontinuing the daily treatment. Comprehensive fb-PMT safety assessments demonstrated excellent safety and tolerability at multiple folds above the anticipated human therapeutic doses. Lastly, our genome-wide microarray screens demonstrated that fb-PMT works through the molecular interference mechanism with multiple signaling pathways contributing to growth and survival of leukemic cells.Conclusion: our preclinical findings of the potent anticancer activities of fb-PMT and its favorable safety profiles warrant its clinical investigation for the effective and safe management of AML.

show abstract

Expression and clinical significance of SNAI1 and ZEB1 genes in acute myeloid leukemia patients

Cited by 11 publications

References 23 publications

Bone marrow overexpression of SNAI1 is an early indicator of intrinsic drug resistance in patients with de novo acute myeloid leukemia

Bone marrow overexpression of SNAI1 is an early indicator of intrinsic drug resistance in patients with de novo acute myeloid leukemia

MALAT-1 regulates the AML progression by promoting the m6A modification of ZEB1

A Novel Fluorobenzyl Polyethylene Glycol Conjucated Tetraiodothyroacetic Acid (fb-PMT), Targeting Thyrointegrin αvβ3 in Treatment Acute Myeloid Leukemia

Contact Info

Product

Resources

About