scholarly journals HDAC8: A Promising Therapeutic Target for Acute Myeloid Leukemia

2020 ◽  
Vol 8 ◽  
Author(s):  
Marco Spreafico ◽  
Alicja M. Gruszka ◽  
Debora Valli ◽  
Mara Mazzola ◽  
Gianluca Deflorian ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Therapeutic Target ◽  
Myeloid Leukemia ◽  
Promising Therapeutic Target ◽  
Acute Myeloid

scholarly journals HMGB1: an important regulator of myeloid differentiation and acute myeloid leukemia as well as a promising therapeutic target

2020 ◽  
Vol 99 (1) ◽  
pp. 107-118
Author(s):  
Lulu Liu ◽  
Jingjing Zhang ◽  
Xianning Zhang ◽  
Panpan Cheng ◽  
Lei Liu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Acute Myeloid Leukemia ◽  
Therapeutic Effect ◽  
Therapeutic Target ◽  
Myeloid Leukemia ◽  
Myeloid Differentiation ◽  
List Type ◽  
Promising Therapeutic Target ◽  
Hmgb1 Expression ◽  
Acute Myeloid

Abstract High mobility group box 1 (HMGB1) is a non-histone nuclear protein which has been intensively studied in various physiological and pathological processes including leukemia. Here in this study, we further demonstrated that HMGB1 presents higher expression in the bone marrow mononuclear cells of acute myeloid leukemia (AML) patients compared with the normal controls and contributes to the AML pathogenesis and progression by inhibiting apoptosis, facilitating proliferation, and inducing myeloid differentiation blockade of AML cells. Mechanistic investigation revealed that transforming growth factor beta-induced (TGFBI) acts as a potential downstream target of HMGB1 and lentivirus-mediated knockdown of TGFBI expression impaired phorbol-12-myristate-13-acetate (PMA) and all-trans retinoic acid (ATRA)–induced myeloid differentiation of AML cell lines. On the other hand, chidamide, an orally histone deacetylase inhibitor, decreases HMGB1 expression significantly in AML cells with concomitant upregulation of TGFBI expression, and confers therapeutic effect on AML by inducing cell differentiation, apoptosis and inhibiting cell proliferation. In conclusion, our findings provide additional insights that HMGB1 is a promising therapeutic target of AML, and also present experimental evidence for the clinical application of chidamide as a novel agent in AML therapy by downregulating HMGB1 expression. Key messages HMGB1 induces cell proliferation and myeloid differentiation blockade and inhibits apoptosis of AML cells. TGFBI acts as a potential target of HMGB1. Chidamide, a selective HDAC inhibitor, confers promising therapeutic effect for AML via downregulating HMGB1 expression.

scholarly journals Arginine dependence of acute myeloid leukemia blast proliferation: a novel therapeutic target

Blood ◽  
2015 ◽  
Vol 125 (15) ◽  
pp. 2386-2396 ◽  
Author(s):  
Francis Mussai ◽  
Sharon Egan ◽  
Joseph Higginbotham-Jones ◽  
Tracey Perry ◽  
Andrew Beggs ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Therapeutic Target ◽  
Myeloid Leukemia ◽  
Leukemia Blast ◽  
Key Points ◽  
Acute Myeloid Leukemia Blast ◽  
Acute Myeloid ◽  
Novel Therapeutic

Key Points Arginase depletion with BCT-100 pegylated recombinant human arginase is cytotoxic to AML blasts.

scholarly journals The retinoic acid receptor co-factor NRIP1 is uniquely upregulated and represents a therapeutic target in acute myeloid leukemia with chromosome 3q rearrangements

Haematologica ◽  
2021 ◽  
Author(s):  
Sarah Grasedieck ◽  
Ariene Cabantog ◽  
Liam MacPhee ◽  
Junbum Im ◽  
Christoph Ruess ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Therapeutic Target ◽  
Myeloid Leukemia ◽  
Integration Site ◽  
Retinoic Acid Receptor ◽  
Aberrant Expression ◽  
Interacting Protein ◽  
Disease Subtype ◽  
Non Coding Rna ◽  
Acute Myeloid

Aberrant expression of Ecotropic Viral Integration Site 1 (EVI1) is a hallmark of acute myeloid leukemia (AML) with inv(3) or t(3;3), which is a disease subtype with especially poor outcome. In studying transcriptomes from AML patients with chromosome 3q rearrangements, we identified a significant upregulation of the Nuclear Receptor Interacting Protein 1 (NRIP1) as well as its adjacent non-coding RNA LOC101927745. Utilizing transcriptomic and epigenomic data from over 900 primary patient samples as well as genetic and transcriptional engineering approaches, we have identified several mechanisms that can lead to upregulation of NRIP1 in AML. We hypothesize that the LOC101927745 transcription start site harbors a context-dependent enhancer that is bound by EVI1, causing upregulation of NRIP1 in AML with chr3 abnormalities. Furthermore, we show that NRIP1 knockdown negatively affects the proliferation and survival of 3q-rearranged AML cells and increases their sensitivity towards ATRA, suggesting that NRIP1 is relevant for the pathogenesis of inv(3)/t(3;3) AML and could serve as a novel therapeutic target in myeloid malignancies with 3q abnormalities.

scholarly journals EGFL7 Antagonizes NOTCH Signaling and Represents a Novel Therapeutic Target in Acute Myeloid Leukemia

2019 ◽  
Vol 26 (3) ◽  
pp. 669-678
Author(s):  
Marius Bill ◽  
Aparna Pathmanathan ◽  
Malith Karunasiri ◽  
Changxian Shen ◽  
Matthew H. Burke ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Notch Signaling ◽  
Therapeutic Target ◽  
Myeloid Leukemia ◽  
Acute Myeloid ◽  
Novel Therapeutic

scholarly journals HDAC1 Is a Required Cofactor of CBFβ-SMMHC and a Potential Therapeutic Target in Inversion 16 Acute Myeloid Leukemia

2019 ◽  
Vol 17 (6) ◽  
pp. 1241-1252 ◽  
Author(s):  
Lisa E. Richter ◽  
Yiqian Wang ◽  
Michelle E. Becker ◽  
Rachel A. Coburn ◽  
Jacob T. Williams ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Therapeutic Target ◽  
Myeloid Leukemia ◽  
Potential Therapeutic Target ◽  
Acute Myeloid

scholarly journals Correction: Corrigendum: SAMHD1 is a biomarker for cytarabine response and a therapeutic target in acute myeloid leukemia

2017 ◽  
Vol 23 (6) ◽  
pp. 788-788
Author(s):  
Constanze Schneider ◽  
Thomas Oellerich ◽  
Hanna-Mari Baldauf ◽  
Sarah-Marie Schwarz ◽  
Dominique Thomas ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Therapeutic Target ◽  
Myeloid Leukemia ◽  
Acute Myeloid
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