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DocT posted an update in the group Acute Myeloid Leukemia AML Advocate Network
Hoping vitamin D (in high doses) will have an inhibitory effect on AML cell proliferation, as this 2013 article states, ” these data suggest that 25(OH) vitamin D3 exerts both direct anti-proliferative effects on leukemia cells and direct/indirect leukemia inhibitory microenvironment reprograming activities”
25(OH) Vitamin D3 Affects Acute Myeloid Leukemia Cell Proliferation | Blood JournalWe recently demonstrated that acute myeloid leukemia (AML) patients with insufficient serum 25(OH) vitamin D3 levels had a worse outcome following intensive induction therapy. However, the mechanisms by which 25(OH) vitamin D3 and its metabolites exert these effects are poorly understood. We utilized in vitro systems with orthogonal genomic and computational approaches to delineate leukemia-specific vitamin D molecular targets that may contribute to its activities. To achieve this goal, we systematically investigated vitamin D anti-proliferative effects using a genomically-annotated panel of human leukemia cell lines, including lines with genetic alterations that are commonly observed in patients. Since the genetic diversity of these cell lines reflects many of the alterations found in AML patients, we hypothesized that they collectively represent a model system to replicate candidate anti-leukemia drug effects. Specifically, we cultured 40 leukemia cell lines with and without 25(OH) vitamin D3 in a dose- and time-dependent manner for 72 hours and used high-throughput (HT) cell-based assays to simultaneously measure multiple modalities/ parameters related to cell proliferation and cytotoxicity (i.e. combining several HT assay chemistries to simultaneously assess cell number, viability, cytotoxicity and caspase activation events). Six AML cell lines (THP-1, MV4;11, MOLM-6, MOLM-13, EOL-1, JK-1) that responded to 25(OH) vitamin D3 treatment were identified and selected for multi-parametric RNA-Seq studies (NB 200nM Vitamin D treatment or vehicle control for 24 hours). Total RNA was extracted and analyzed by the Illumina HiSeq 2500 sequencing platform and mRNA, microRNA and ncRNAs were unambiguously quantitated. Utilizing gene expression profiles and in silico computational modeling of canonical or putative vitamin D receptor elements (VDRE) transcription factor promoter binding sites, we (1) identified a conserved/core gene transcriptional signature and (2) subsequently developed a vitamin D – genetic inference model. Gene enrichment analysis of the inferred network model identified genes involved in abnormal hematopoiesis, proliferation and differentiation, interleukin secretion, leukocyte migration, and bone marrow cell morphology and/or development. Notably, our data identified several 25(OH) vitamin D3 transcriptional regulatory cascades that converge on ETS2, JUND, NCOA4, RXR4, WT1, and ZFP30 transcription factors. Furthermore, we also demonstrate temporal and spatial regulation of protein kinases CAMK1 and FGFR, cytokine and growth factors (cAMP, CCL2, IL-8 and TNF), and cell differentiation markers (CD14, CD97, FCGR2A, IL3RG, IL7R, ITGAM, THBD). In summary, these data suggest that 25(OH) vitamin D3 exerts both direct anti-proliferative effects on leukemia cells and direct/indirect leukemia inhibitory microenvironment reprograming activities and better clarify the complex molecular mechanisms underlying the therapeutic activity of 25(OH) vitamin D3 in AML.Disclosures: No relevant conflicts of interest to declare.
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8Ting posted an update in the group Acute Myeloid Leukemia AML Advocate Network
I am looking for information regarding the safety and efficacy of using Zarxio in improving WBC situation after chemo to treat Myeloid for a friend, His doctor suggested starting Zarxio inject but did not give much more about why and how effective it has been and what is the side effect. If anyone here knows more and can share, that will be great.
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Thank you very much 8Ting for reaching out. I do not have personal experience with this drug, but WeHeal partners with other organizations to make sure you find the answer you need. I did find some answers at the link attached, but you may also want to contact one of the advocates at our partner Cancer Commons (CancerCommons.org). Just go to the patients tab and fill out the ASK form, and one of the advocates there will respond and hopefully will be able to give you more details. The leukemia lymphoma society also has an advocate center, and often contacting the pharma company who makes the drug can be the best source of info. https://www.everydayhealth.com/drugs/filgrastim
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Jeff Jones posted an update in the group Acute Myeloid Leukemia AML Advocate Network
Do you have or know someone who is a Sibling who has found the battle: “Oh Brother: Being the Sibling of a Kid With Cancer” :
Oh Brother: Being the Sibling of a Kid With Cancer – The Seany FoundationOh Brother: Being the Sibling of a Kid With Cancer – The Seany Foundation -
Eric Drew posted an update in the group Acute Myeloid Leukemia AML Advocate Network
Improved Survival With Integration of Chinese Herbal Medicine Therapy in Patients With Acute Myeloid Leukemia: A Nationwide Population-Based Cohort StudyIntegrative Cancer Therapies – Tom Fleischer, Tung-Ti Chang, Jen-Huai Chiang, Mao-Feng Sun, Hung-Rong Yen, 2017Purpose. Acute myeloid leukemia (AML) is the most deadly subtype of leukemia, and many patients with this disease seek other complementary therapies, one of whi… -
DocT posted an update in the group Acute Myeloid Leukemia AML Advocate Network
Hoping vitamin D (in high doses) will have an inhibitory effect on AML cell proliferation, as this 2013 article states, ” these data suggest that 25(OH) vitamin D3 exerts both direct anti-proliferative effects on leukemia cells and direct/indirect leukemia inhibitory microenvironment reprograming activities”
25(OH) Vitamin D3 Affects Acute Myeloid Leukemia Cell Proliferation | Blood JournalWe recently demonstrated that acute myeloid leukemia (AML) patients with insufficient serum 25(OH) vitamin D3 levels had a worse outcome following intensive induction therapy. However, the mechanisms by which 25(OH) vitamin D3 and its metabolites exert these effects are poorly understood. We utilized in vitro systems with orthogonal genomic and computational approaches to delineate leukemia-specific vitamin D molecular targets that may contribute to its activities. To achieve this goal, we systematically investigated vitamin D anti-proliferative effects using a genomically-annotated panel of human leukemia cell lines, including lines with genetic alterations that are commonly observed in patients. Since the genetic diversity of these cell lines reflects many of the alterations found in AML patients, we hypothesized that they collectively represent a model system to replicate candidate anti-leukemia drug effects. Specifically, we cultured 40 leukemia cell lines with and without 25(OH) vitamin D3 in a dose- and time-dependent manner for 72 hours and used high-throughput (HT) cell-based assays to simultaneously measure multiple modalities/ parameters related to cell proliferation and cytotoxicity (i.e. combining several HT assay chemistries to simultaneously assess cell number, viability, cytotoxicity and caspase activation events). Six AML cell lines (THP-1, MV4;11, MOLM-6, MOLM-13, EOL-1, JK-1) that responded to 25(OH) vitamin D3 treatment were identified and selected for multi-parametric RNA-Seq studies (NB 200nM Vitamin D treatment or vehicle control for 24 hours). Total RNA was extracted and analyzed by the Illumina HiSeq 2500 sequencing platform and mRNA, microRNA and ncRNAs were unambiguously quantitated. Utilizing gene expression profiles and in silico computational modeling of canonical or putative vitamin D receptor elements (VDRE) transcription factor promoter binding sites, we (1) identified a conserved/core gene transcriptional signature and (2) subsequently developed a vitamin D – genetic inference model. Gene enrichment analysis of the inferred network model identified genes involved in abnormal hematopoiesis, proliferation and differentiation, interleukin secretion, leukocyte migration, and bone marrow cell morphology and/or development. Notably, our data identified several 25(OH) vitamin D3 transcriptional regulatory cascades that converge on ETS2, JUND, NCOA4, RXR4, WT1, and ZFP30 transcription factors. Furthermore, we also demonstrate temporal and spatial regulation of protein kinases CAMK1 and FGFR, cytokine and growth factors (cAMP, CCL2, IL-8 and TNF), and cell differentiation markers (CD14, CD97, FCGR2A, IL3RG, IL7R, ITGAM, THBD). In summary, these data suggest that 25(OH) vitamin D3 exerts both direct anti-proliferative effects on leukemia cells and direct/indirect leukemia inhibitory microenvironment reprograming activities and better clarify the complex molecular mechanisms underlying the therapeutic activity of 25(OH) vitamin D3 in AML.Disclosures: No relevant conflicts of interest to declare.
Thanks DocT for posting this, and please let us know how the study turns out! Our goal is to make this data available for all AML treatment providers, patients, and researchers! We will be organizing an oversight committee for this community to do just that!