The Experts below are selected from a list of 285 Experts worldwide ranked by ideXlab platform
Hao Huang - One of the best experts on this subject based on the ideXlab platform.
-
Homoharringtonine exhibits potent anti tumor effect and modulates dna epigenome in acute myeloid leukemia by targeting sp1 tet1 5hmc
Haematologica, 2020Co-Authors: Lei Dong, Ying Qing, Xiaolan Deng, Yile Zhou, Hao Huang, Xi Jiang, Dongling Zou, Chao Shen, Li Han, Miao SunAbstract:Homoharringtonine, a plant alkaloid, has been reported to suppress protein synthesis and has been approved by the US Food and Drug Administration for the treatment of chronic myeloid leukemia. Here we show that in acute myeloid leukemia (AML), Homoharringtonine potently inhibits cell growth/viability and induces cell cycle arrest and apoptosis, significantly inhibits disease progression in vivo, and substantially prolongs survival of mice bearing murine or human AML. Strikingly, Homoharringtonine treatment dramatically decreases global DNA 5-hydroxymethylcytosine abundance through targeting the SP1/TET1 axis, and TET1 depletion mimics Homoharringtonine’s therapeutic effects in AML. Our further 5hmC-seq and RNA-seq analyses, followed by a series of validation and functional studies, suggest that FLT3 is a critical down-stream target of Homoharringtonine/SP1/TET1/5hmC signaling, and suppression of FLT3 and its downstream targets (e.g. MYC) contributes to the high sensitivity of FLT3-mutated AML cells to Homoharringtonine. Collectively, our studies uncover a previously unappreciated DNA epigenome-related mechanism underlying the potent antileukemic effect of Homoharringtonine, which involves suppression of the SP1/TET1/5hmC/FLT3/MYC signaling pathways in AML. Our work also highlights the particular promise of clinical application of Homoharringtonine to treat human AML with FLT3 mutations, which accounts for more than 30% of total cases of AML.
-
Homoharringtonine exhibits potent anti-tumor effect and modulates DNA epigenome in acute myeloid leukemia by targeting SP1/TET1/5hmC.
Haematologica, 2019Co-Authors: Lei Dong, Ying Qing, Xiaolan Deng, Yile Zhou, Hao HuangAbstract:Homoharringtonine, a plant alkaloid, has been reported to suppress protein synthesis and has been approved by the US Food and Drug Administration for the treatment of chronic myeloid leukemia. Here we show that in acute myeloid leukemia (AML), Homoharringtonine potently inhibits cell growth/viability and induces cell cycle arrest and apoptosis, significantly inhibits disease progression in vivo, and substantially prolongs survival of mice bearing murine or human AML. Strikingly, Homoharringtonine treatment dramatically decreases global DNA 5-hydroxymethylcytosine abundance through targeting the SP1/TET1 axis, and TET1 depletion mimics Homoharringtonine’s therapeutic effects in AML. Our further 5hmC-seq and RNA-seq analyses, followed by a series of validation and functional studies, suggest that FLT3 is a critical down-stream target of Homoharringtonine/SP1/TET1/5hmC signaling, and suppression of FLT3 and its downstream targets (e.g. MYC) contributes to the high sensitivity of FLT3-mutated AML cells to Homoharringtonine. Collectively, our studies uncover a previously unappreciated DNA epigenome-related mechanism underlying the potent antileukemic effect of Homoharringtonine, which involves suppression of the SP1/TET1/5hmC/FLT3/MYC signaling pathways in AML. Our work also highlights the particular promise of clinical application of Homoharringtonine to treat human AML with FLT3 mutations, which accounts for more than 30% of total cases of AML.
Lei Dong - One of the best experts on this subject based on the ideXlab platform.
-
Homoharringtonine exhibits potent anti tumor effect and modulates dna epigenome in acute myeloid leukemia by targeting sp1 tet1 5hmc
Haematologica, 2020Co-Authors: Lei Dong, Ying Qing, Xiaolan Deng, Yile Zhou, Hao Huang, Xi Jiang, Dongling Zou, Chao Shen, Li Han, Miao SunAbstract:Homoharringtonine, a plant alkaloid, has been reported to suppress protein synthesis and has been approved by the US Food and Drug Administration for the treatment of chronic myeloid leukemia. Here we show that in acute myeloid leukemia (AML), Homoharringtonine potently inhibits cell growth/viability and induces cell cycle arrest and apoptosis, significantly inhibits disease progression in vivo, and substantially prolongs survival of mice bearing murine or human AML. Strikingly, Homoharringtonine treatment dramatically decreases global DNA 5-hydroxymethylcytosine abundance through targeting the SP1/TET1 axis, and TET1 depletion mimics Homoharringtonine’s therapeutic effects in AML. Our further 5hmC-seq and RNA-seq analyses, followed by a series of validation and functional studies, suggest that FLT3 is a critical down-stream target of Homoharringtonine/SP1/TET1/5hmC signaling, and suppression of FLT3 and its downstream targets (e.g. MYC) contributes to the high sensitivity of FLT3-mutated AML cells to Homoharringtonine. Collectively, our studies uncover a previously unappreciated DNA epigenome-related mechanism underlying the potent antileukemic effect of Homoharringtonine, which involves suppression of the SP1/TET1/5hmC/FLT3/MYC signaling pathways in AML. Our work also highlights the particular promise of clinical application of Homoharringtonine to treat human AML with FLT3 mutations, which accounts for more than 30% of total cases of AML.
-
Homoharringtonine exhibits potent anti-tumor effect and modulates DNA epigenome in acute myeloid leukemia by targeting SP1/TET1/5hmC.
Haematologica, 2019Co-Authors: Lei Dong, Ying Qing, Xiaolan Deng, Yile Zhou, Hao HuangAbstract:Homoharringtonine, a plant alkaloid, has been reported to suppress protein synthesis and has been approved by the US Food and Drug Administration for the treatment of chronic myeloid leukemia. Here we show that in acute myeloid leukemia (AML), Homoharringtonine potently inhibits cell growth/viability and induces cell cycle arrest and apoptosis, significantly inhibits disease progression in vivo, and substantially prolongs survival of mice bearing murine or human AML. Strikingly, Homoharringtonine treatment dramatically decreases global DNA 5-hydroxymethylcytosine abundance through targeting the SP1/TET1 axis, and TET1 depletion mimics Homoharringtonine’s therapeutic effects in AML. Our further 5hmC-seq and RNA-seq analyses, followed by a series of validation and functional studies, suggest that FLT3 is a critical down-stream target of Homoharringtonine/SP1/TET1/5hmC signaling, and suppression of FLT3 and its downstream targets (e.g. MYC) contributes to the high sensitivity of FLT3-mutated AML cells to Homoharringtonine. Collectively, our studies uncover a previously unappreciated DNA epigenome-related mechanism underlying the potent antileukemic effect of Homoharringtonine, which involves suppression of the SP1/TET1/5hmC/FLT3/MYC signaling pathways in AML. Our work also highlights the particular promise of clinical application of Homoharringtonine to treat human AML with FLT3 mutations, which accounts for more than 30% of total cases of AML.
Jorge E. Cortes - One of the best experts on this subject based on the ideXlab platform.
-
Homoharringtonine omacetaxine mepesuccinate the long and winding road to food and drug administration approval
Clinical Lymphoma Myeloma & Leukemia, 2013Co-Authors: Hagop M. Kantarjian, Susan Obrien, Jorge E. CortesAbstract:Homoharringtonine/omacetaxine is a unique agent with a long history of research development. It has been recently approved by the Food and Drug Administration for the treatment of chronic myeloid leukemia after failure of 2 or more tyrosine kinase inhibitors. Research with this agent has spanned over 40 years, with many instructive lessons to cancer research, which are summarized in this review.
-
Homoharringtonine/omacetaxine mepesuccinate: the long and winding road to food and drug administration approval.
Clinical lymphoma myeloma & leukemia, 2013Co-Authors: Hagop M. Kantarjian, Susan O'brien, Jorge E. CortesAbstract:Homoharringtonine/omacetaxine is a unique agent with a long history of research development. It has been recently approved by the Food and Drug Administration for the treatment of chronic myeloid leukemia after failure of 2 or more tyrosine kinase inhibitors. Research with this agent has spanned over 40 years, with many instructive lessons to cancer research, which are summarized in this review.
-
A phase II open-label study of the intravenous administration of Homoharringtonine in the treatment of myelodysplastic syndrome.
European journal of cancer care, 2013Co-Authors: Naval Daver, Arturo Vega-ruiz, Hagop M. Kantarjian, Zeev Estrov, Alessandra Ferrajoli, Steve Kornblau, Srdan Verstovsek, Guillermo Garcia-manero, Jorge E. CortesAbstract:Homoharringtonine is an alkaloid inhibitor of protein synthesis with activity in myeloid malignancies. We report a phase II pilot study of Homoharringtonine in myelodysplastic syndrome (MDS). Induction consisted of Homoharringtonine at 2.5 mg/m(2) via continuous infusion for 7 days. Maintenance was given every 4 weeks. Nine patients were enrolled: five with refractory anaemia with excess blasts, two with refractory anaemia with excess blasts in transformation, one each with refractory anaemia and chronic myelomonocytic leukaemia respectively. Median age was 70 years (55-84) and 6 (66%) were male. Per International Prognostic Scoring System (IPSS) two patients were intermediate-1, five intermediate-2 and two high-risk. Median chemotherapy courses were one (1-3). One patient (11%) responded with complete haematological and cytogenetic remission after one course. Eight patients did not respond (four had stable disease, two progressed to acute leukaemia and two died during induction - from aspergillus pneumonia and intracerebral haemorrhage respectively). Grade 3/4 myelosuppression seen in 56% (5/9). Serious non-haematological toxicities included one case of grade 4 left bundle branch heart block and one grade 3 nephrotoxicity. Median time between courses was 42 days (35-72 days). In conclusion Homoharringtonine might have clinical activity in some patients with MDS.
Miao Sun - One of the best experts on this subject based on the ideXlab platform.
-
Homoharringtonine exhibits potent anti tumor effect and modulates dna epigenome in acute myeloid leukemia by targeting sp1 tet1 5hmc
Haematologica, 2020Co-Authors: Lei Dong, Ying Qing, Xiaolan Deng, Yile Zhou, Hao Huang, Xi Jiang, Dongling Zou, Chao Shen, Li Han, Miao SunAbstract:Homoharringtonine, a plant alkaloid, has been reported to suppress protein synthesis and has been approved by the US Food and Drug Administration for the treatment of chronic myeloid leukemia. Here we show that in acute myeloid leukemia (AML), Homoharringtonine potently inhibits cell growth/viability and induces cell cycle arrest and apoptosis, significantly inhibits disease progression in vivo, and substantially prolongs survival of mice bearing murine or human AML. Strikingly, Homoharringtonine treatment dramatically decreases global DNA 5-hydroxymethylcytosine abundance through targeting the SP1/TET1 axis, and TET1 depletion mimics Homoharringtonine’s therapeutic effects in AML. Our further 5hmC-seq and RNA-seq analyses, followed by a series of validation and functional studies, suggest that FLT3 is a critical down-stream target of Homoharringtonine/SP1/TET1/5hmC signaling, and suppression of FLT3 and its downstream targets (e.g. MYC) contributes to the high sensitivity of FLT3-mutated AML cells to Homoharringtonine. Collectively, our studies uncover a previously unappreciated DNA epigenome-related mechanism underlying the potent antileukemic effect of Homoharringtonine, which involves suppression of the SP1/TET1/5hmC/FLT3/MYC signaling pathways in AML. Our work also highlights the particular promise of clinical application of Homoharringtonine to treat human AML with FLT3 mutations, which accounts for more than 30% of total cases of AML.
Ying Qing - One of the best experts on this subject based on the ideXlab platform.
-
Homoharringtonine exhibits potent anti tumor effect and modulates dna epigenome in acute myeloid leukemia by targeting sp1 tet1 5hmc
Haematologica, 2020Co-Authors: Lei Dong, Ying Qing, Xiaolan Deng, Yile Zhou, Hao Huang, Xi Jiang, Dongling Zou, Chao Shen, Li Han, Miao SunAbstract:Homoharringtonine, a plant alkaloid, has been reported to suppress protein synthesis and has been approved by the US Food and Drug Administration for the treatment of chronic myeloid leukemia. Here we show that in acute myeloid leukemia (AML), Homoharringtonine potently inhibits cell growth/viability and induces cell cycle arrest and apoptosis, significantly inhibits disease progression in vivo, and substantially prolongs survival of mice bearing murine or human AML. Strikingly, Homoharringtonine treatment dramatically decreases global DNA 5-hydroxymethylcytosine abundance through targeting the SP1/TET1 axis, and TET1 depletion mimics Homoharringtonine’s therapeutic effects in AML. Our further 5hmC-seq and RNA-seq analyses, followed by a series of validation and functional studies, suggest that FLT3 is a critical down-stream target of Homoharringtonine/SP1/TET1/5hmC signaling, and suppression of FLT3 and its downstream targets (e.g. MYC) contributes to the high sensitivity of FLT3-mutated AML cells to Homoharringtonine. Collectively, our studies uncover a previously unappreciated DNA epigenome-related mechanism underlying the potent antileukemic effect of Homoharringtonine, which involves suppression of the SP1/TET1/5hmC/FLT3/MYC signaling pathways in AML. Our work also highlights the particular promise of clinical application of Homoharringtonine to treat human AML with FLT3 mutations, which accounts for more than 30% of total cases of AML.
-
Homoharringtonine exhibits potent anti-tumor effect and modulates DNA epigenome in acute myeloid leukemia by targeting SP1/TET1/5hmC.
Haematologica, 2019Co-Authors: Lei Dong, Ying Qing, Xiaolan Deng, Yile Zhou, Hao HuangAbstract:Homoharringtonine, a plant alkaloid, has been reported to suppress protein synthesis and has been approved by the US Food and Drug Administration for the treatment of chronic myeloid leukemia. Here we show that in acute myeloid leukemia (AML), Homoharringtonine potently inhibits cell growth/viability and induces cell cycle arrest and apoptosis, significantly inhibits disease progression in vivo, and substantially prolongs survival of mice bearing murine or human AML. Strikingly, Homoharringtonine treatment dramatically decreases global DNA 5-hydroxymethylcytosine abundance through targeting the SP1/TET1 axis, and TET1 depletion mimics Homoharringtonine’s therapeutic effects in AML. Our further 5hmC-seq and RNA-seq analyses, followed by a series of validation and functional studies, suggest that FLT3 is a critical down-stream target of Homoharringtonine/SP1/TET1/5hmC signaling, and suppression of FLT3 and its downstream targets (e.g. MYC) contributes to the high sensitivity of FLT3-mutated AML cells to Homoharringtonine. Collectively, our studies uncover a previously unappreciated DNA epigenome-related mechanism underlying the potent antileukemic effect of Homoharringtonine, which involves suppression of the SP1/TET1/5hmC/FLT3/MYC signaling pathways in AML. Our work also highlights the particular promise of clinical application of Homoharringtonine to treat human AML with FLT3 mutations, which accounts for more than 30% of total cases of AML.