scholarly journals Genome-scale integrated analysis to identify prospective molecular mechanisms and therapeutic targets in isocitrate dehydrogenase 2 R140Q-mutated acute myeloid leukemia

2019 ◽  
Author(s):  
Rui Huang ◽  
Xiwen Liao ◽  
Jing Li ◽  
Jiemin Wei ◽  
Xiayun Su ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Isocitrate Dehydrogenase ◽  
Myeloid Leukemia ◽  
Molecular Mechanisms ◽  
Therapeutic Targets ◽  
Integrated Analysis ◽  
Isocitrate Dehydrogenase 2 ◽  
Genome Scale ◽  
Acute Myeloid

scholarly journals Mutations in the isocitrate dehydrogenase 2 gene and IDH1 SNP 105C > T have a prognostic value in acute myeloid leukemia

2014 ◽  
Vol 2 (1) ◽  
Author(s):  
Kerstin Willander ◽  
Ingrid Jakobsen Falk ◽  
Roza Chaireti ◽  
Esbjörn Paul ◽  
Monica Hermansson ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Isocitrate Dehydrogenase ◽  
Myeloid Leukemia ◽  
Prognostic Value ◽  
Isocitrate Dehydrogenase 2 ◽  
Acute Myeloid

scholarly journals Thyroiditis: A Rare Manifestation of Enasidenib-Induced Differentiation Syndrome

2020 ◽  
Vol 13 (2) ◽  
pp. 583-587
Author(s):  
Pavan Annamaraju ◽  
Swathi Gopishetty ◽  
Naga Goparaju ◽  
Matthew Beasey ◽  
Vamsi Kota ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Pleural Effusion ◽  
Isocitrate Dehydrogenase ◽  
Myeloid Leukemia ◽  
Induced Differentiation ◽  
Common Presentation ◽  
Isocitrate Dehydrogenase 2 ◽  
Rare Manifestation ◽  
Idh2 Mutation ◽  
Acute Myeloid

Enasidenib is an FDA-approved isocitrate dehydrogenase 2 (IDH2) inhibitor, which is used in the treatment of acute myeloid leukemia (AML). We present a case of AML with an IDH2 mutation treated with a regimen of enasidenib and 5-azacitidine, where thyroiditis was noted to be a part of differentiation syndrome. The patient is a 77-year-old woman with IDH2-mutated AML who had initially been started on 100 mg of enasidenib and then presented with dyspnea and was diagnosed with pleural effusion – a common presentation with enasidenib – but was also noted to have thyroiditis. She was started on steroids, but due to continued hyperbilirubinemia and thyroiditis, her dose of enasidenib was reduced to half, which resulted in clinical improvement. This case demonstrates thyroiditis as one of the rare manifestations in the treatment of AML with enasidenib-induced differentiation syndrome.

scholarly journals NUP-98 Rearrangements Led to the Identification of Candidate Biomarkers for Primary Induction Failure in Pediatric Acute Myeloid Leukemia

2021 ◽  
Vol 22 (9) ◽  
pp. 4575
Author(s):  
Vincenza Barresi ◽  
Virginia Di Bella ◽  
Nellina Andriano ◽  
Anna Provvidenza Privitera ◽  
Paola Bonaccorso ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Mutational Analysis ◽  
Integrated Analysis ◽  
Induction Phase ◽  
Pediatric Acute Myeloid Leukemia ◽  
Expression Arrays ◽  
Primary Induction ◽  
Induction Failure ◽  
Acute Myeloid

Conventional chemotherapy for acute myeloid leukemia regimens generally encompass an intensive induction phase, in order to achieve a morphological remission in terms of bone marrow blasts (<5%). The majority of cases are classified as Primary Induction Response (PIR); unfortunately, 15% of children do not achieve remission and are defined Primary Induction Failure (PIF). This study aims to characterize the gene expression profile of PIF in children with Acute Myeloid Leukemia (AML), in order to detect molecular pathways dysfunctions and identify potential biomarkers. Given that NUP98-rearrangements are enriched in PIF-AML patients, we investigated the association of NUP98-driven genes in primary chemoresistance. Therefore, 85 expression arrays, deposited on GEO database, and 358 RNAseq AML samples, from TARGET program, were analyzed for “Differentially Expressed Genes” (DEGs) between NUP98+ and NUP98-, identifying 110 highly confident NUP98/PIF-associated DEGs. We confirmed, by qRT-PCR, the overexpression of nine DEGs, selected on the bases of the diagnostic accuracy, in a local cohort of PIF patients: SPINK2, TMA7, SPCS2, CDCP1, CAPZA1, FGFR1OP2, MAN1A2, NT5C3A and SRP54. In conclusion, the integrated analysis of NUP98 mutational analysis and transcriptome profiles allowed the identification of novel putative biomarkers for the prediction of PIF in AML.

scholarly journals Isocitrate dehydrogenase 1 and 2 mutations, 2‐hydroxyglutarate levels, and response to standard chemotherapy for patients with newly diagnosed acute myeloid leukemia

Cancer ◽  
2018 ◽  
Vol 125 (4) ◽  
pp. 541-549 ◽  
Author(s):  
Andrew M. Brunner ◽  
Donna S. Neuberg ◽  
Seth A. Wander ◽  
Hossein Sadrzadeh ◽  
Karen K. Ballen ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Isocitrate Dehydrogenase ◽  
Myeloid Leukemia ◽  
Newly Diagnosed ◽  
Standard Chemotherapy ◽  
Isocitrate Dehydrogenase 1 ◽  
Acute Myeloid

scholarly journals A Genome-Wide Aberrant RNA Splicing in Patients with Acute Myeloid Leukemia Identifies Novel Potential Disease Markers and Therapeutic Targets

2013 ◽  
Vol 20 (5) ◽  
pp. 1135-1145 ◽  
Author(s):  
Sophia Adamia ◽  
Benjamin Haibe-Kains ◽  
Patrick M. Pilarski ◽  
Michal Bar-Natan ◽  
Samuel Pevzner ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Rna Splicing ◽  
Myeloid Leukemia ◽  
Therapeutic Targets ◽  
Disease Markers ◽  
Genome Wide ◽  
A Genome ◽  
Aberrant Rna ◽  
Acute Myeloid

scholarly journals WTIP upregulates FOXO3a and induces apoptosis through PUMA in acute myeloid leukemia

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Yunqi Zhu ◽  
Xiangmin Tong ◽  
Ying Wang ◽  
Xiaoya Lu
Keyword(s):  
Acute Myeloid Leukemia ◽  
Tumor Suppressor ◽  
Transcriptional Activation ◽  
Myeloid Leukemia ◽  
Molecular Mechanisms ◽  
Nuclear Translocation ◽  
Hematologic Malignancy ◽  
Apoptotic Pathway ◽  
Acute Myeloid

AbstractAcute myeloid leukemia (AML) is an aggressive and heterogeneous clonal hematologic malignancy for which novel therapeutic targets and strategies are required. Emerging evidence suggests that WTIP is a candidate tumor suppressor. However, the molecular mechanisms of WTIP in leukemogenesis have not been explored. Here, we report that WTIP expression is significantly reduced both in AML cell lines and clinical specimens compared with normal controls, and low levels of WTIP correlate with decreased overall survival in AML patients. Overexpression of WTIP inhibits cell proliferation and induces apoptosis both in vitro and in vivo. Mechanistic studies reveal that the apoptotic function of WTIP is mediated by upregulation and nuclear translocation of FOXO3a, a member of Forkhead box O (FOXO) transcription factors involved in tumor suppression. We further demonstrate that WTIP interacts with FOXO3a and transcriptionally activates FOXO3a. Upon transcriptional activation of FOXO3a, its downstream target PUMA is increased, leading to activation of the intrinsic apoptotic pathway. Collectively, our results suggest that WTIP is a tumor suppressor and a potential target for therapeutic intervention in AML.

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