Association between high expression of natural killer related-genes (NCAM/CD94) and early death during induction in children with acute myeloid leukemia

Lonigro, L; Mirabile, Elena; Munda, Silvana; Barchitta, Martina; Bottino, Daria; Fazzio, Agata; Cataldo, Andrea Di; Agodi, Antonella; Schilirò, G

doi:10.1038/leu.2008.46

Cited by 4 publications

(3 citation statements)

References 9 publications

(6 reference statements)

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“…This gene was recently identified as a driver of megakaryocytic leukemia in a mouse DS AMKL model [35]. Neural Cell Adhesion Molecule (NCAM), which was found to be repressed by GATA1, is associated with poorer prognosis in AML [36] and early death in pediatric AML patients [37]. Vascular endothelial growth factor (VEGF) was identified by the ChIP-on-ChIP to be a direct GATA1 target is indicative of poorer prognosis [38] and is also a potential therapeutic target in AML [39].…”

Section: Discussionmentioning

confidence: 99%

Overexpression of GATA1 Confers Resistance to Chemotherapy in Acute Megakaryocytic Leukemia

et al. 2013

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It has been previously shown that acute myeloid leukemia (AML) patients with higher levels of GATA1 expression have poorer outcomes. Furthermore, pediatric Down syndrome (DS) patients with acute megakaryocytic leukemia (AMKL), whose blast cells almost universally harbor somatic mutations in exon 2 of the transcription factor gene GATA1, demonstrate increased overall survival relative to non-DS pediatric patients, suggesting a potential role for GATA1 in chemotherapy response. In this study, we confirmed that amongst non-DS patients, GATA1 transcripts were significantly higher in AMKL blasts compared to blasts from other AML subgroups. Further, GATA1 transcript levels significantly correlated with transcript levels for the anti-apoptotic protein Bcl-xL in our patient cohort. ShRNA knockdown of GATA1 in the megakaryocytic cell line Meg-01 resulted in significantly increased cytarabine (ara-C) and daunorubicin anti-proliferative sensitivities and decreased Bcl-xL transcript and protein levels. Chromatin immunoprecipitation (ChIP) and reporter gene assays demonstrated that the Bcl-x gene (which transcribes the Bcl-xL transcripts) is a bona fide GATA1 target gene in AMKL cells. Treatment of the Meg-01 cells with the histone deacetylase inhibitor valproic acid resulted in down-regulation of both GATA1 and Bcl-xL and significantly enhanced ara-C sensitivity. Furthermore, additional GATA1 target genes were identified by oligonucleotide microarray and ChIP-on-Chip analyses. Our findings demonstrate a role for GATA1 in chemotherapy resistance in non-DS AMKL cells, and identified additional GATA1 target genes for future studies.

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Section: Discussionmentioning

confidence: 99%

Overexpression of GATA1 Confers Resistance to Chemotherapy in Acute Megakaryocytic Leukemia

et al. 2013

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“…SECISBP2L (selenocysteine incorporation), 44 , 45 MAN1A2 (metabolic process), 46 , 47 , 48 , 49 PRPF31 (mRNA splicing), 50 , 51 VASP (cell junction assembly), 52 and SNAPC1 (transcription regulation) 53 , 54 were identified as highly connected gene groups in the PONO network. Moreover, PHTF2 (transcription regulation), 55 SLC11A2 (heme process), 56 PDLIM5 (cell–cell adhesion), 57 , 58 , 59 OTUB1 (adaptive immune system), 60 , 61 , 62 , 63 , 64 and KLRD1 (immune response regulation) 65 , 66 were found in the OPON network (Table 2 ).…”

Section: Discussionmentioning

confidence: 99%

“…65 The higher expression of neural cell adhesion molecule (NCAM) and CD94 was associated with early death in pediatric AML. 66 cell development while normal colony formation of progenitor cells. 71,72 Moreover, in patients with hematologic malignancies after allogeneic hematopoietic stem cell transplantation, an elevated serum ferritin level is a poor prognostic indicator of overall survival and nonrelapse mortality.…”

Section: Phtf2mentioning

confidence: 99%

Differential co‐expression network analysis elucidated genes associated with sensitivity to farnesyltransferase inhibitor and prognosis of acute myeloid leukemia

Kelesoglu,

Kori,

Yilmaz

et al. 2023

Cancer Medicine

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Acute myeloid leukemia (AML) is a heterogeneous disease and the most common form of acute leukemia with a poor prognosis. Due to its complexity, the disease requires the identification of biomarkers for reliable prognosis. To identify potential disease genes that regulate patient prognosis, we used differential co‐expression network analysis and transcriptomics data from relapsed, refractory, and previously untreated AML patients based on their response to treatment in the present study. In addition, we combined functional genomics and transcriptomics data to identify novel and therapeutically potential systems biomarkers for patients who do or do not respond to treatment. As a result, we constructed co‐expression networks for response and non‐response cases and identified a highly interconnected group of genes consisting of SECISBP2L, MAN1A2, PRPF31, VASP, and SNAPC1 in the response network and a group consisting of PHTF2, SLC11A2, PDLIM5, OTUB1, and KLRD1 in the non‐response network, both of which showed high prognostic performance with hazard ratios of 4.12 and 3.66, respectively. Remarkably, ETS1, GATA2, AR, YBX1, and FOXP3 were found to be important transcription factors in both networks. The prognostic indicators reported here could be considered as a resource for identifying tumorigenesis and chemoresistance to farnesyltransferase inhibitor. They could help identify important research directions for the development of new prognostic and therapeutic techniques for AML.

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Early deaths from childhood cancer in Germany 1980-2016

Becker

Graf

Grabow

et al. 2020

Cancer Epidemiology

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Association between high expression of natural killer related-genes (NCAM/CD94) and early death during induction in children with acute myeloid leukemia

Cited by 4 publications

References 9 publications

Overexpression of GATA1 Confers Resistance to Chemotherapy in Acute Megakaryocytic Leukemia

Overexpression of GATA1 Confers Resistance to Chemotherapy in Acute Megakaryocytic Leukemia

Differential co‐expression network analysis elucidated genes associated with sensitivity to farnesyltransferase inhibitor and prognosis of acute myeloid leukemia

Early deaths from childhood cancer in Germany 1980-2016

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