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Pre and post ATRA/VP treatment proteomic and phophoproteomic profiling of AML responders and non-responders

ABSTRACT: Proteome and phosphoproteome raw files from AML patient samples obtained before and after 3 and 8 days of ATRA/valproic acid treatment

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Cell, Blood

DISEASE(S): Acute Leukemia

SUBMITTER: Maria Hernandez-Valladares

LAB HEAD: Maria Hernandez Valladares

PROVIDER: PXD024197 | Pride | 2021-09-10

REPOSITORIES: Pride

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Dataset's files

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			Action	DRS
	AT1-T1_x1.raw	Raw
	AT1-T1_x2.raw	Raw
	AT1-T1_x3.raw	Raw
	AT1-T2_x1.raw	Raw
	AT1-T2_x2.raw	Raw

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1 - 5 of 125

Publications

Proteomic Studies of Primary Acute Myeloid Leukemia Cells Derived from Patients Before and during Disease-Stabilizing Treatment Based on All-Trans Retinoic Acid and Valproic Acid.

Hernandez-Valladares Maria M Wangen Rebecca R Aasebø Elise E Reikvam Håkon H Berven Frode S FS Selheim Frode F Bruserud Øystein Ø

Cancers 20210429 9

All-trans retinoic acid (ATRA) and valproic acid (VP) have been tried in the treatment of non-promyelocytic variants of acute myeloid leukemia (AML). Non-randomized studies suggest that the two drugs can stabilize AML and improve normal peripheral blood cell counts. In this context, we used a proteomic/phosphoproteomic strategy to investigate the in vivo effects of ATRA/VP on human AML cells. Before starting the combined treatment, AML responders showed increased levels of several proteins, espe ...[more]

PMID: 33946813

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Responder and non-responder proteomic and phosphoproteomic profiles to ATRA/Valproic acid before treatment

Project description:Proteomic and phosphoproteomic raw files from responder and non-responder acute myeloid leukemia patient samples before initiation of ATRA/valproic acid treatment

2021-09-10 | PXD024110 | Pride

OCI/AML2 ATRA AND VPA GENE EXPRESSION

Project description:Purpose: Treatment of acute promyelocytic leukemia (APL) with the retinoid, all trans retinoic acid (ATRA), along with standard chemotherapy has significantly improved survival compared to chemotherapy alone1. ATRA mediates its benefit in APL by overcoming the transcriptional block mediated by PML-RAR-alpha fusion oncoprotein, thereby, restoring expression of retinoid response genes2. The therapeutic benefits observed with ATRA treatment in APL have not been achieved in the other more common sub-types of acute myeloblastic leukemia (AML)3. This likely reflects the recruitment of histone deacetylase complexes by other recurrent chromosomal translocations in AML cells4. In this experiment, we evaluated if treatment of the AML cell line, OCI/AML-2, with the histone deacetylase inhibitor, valproic acid (VPA), would alter the expression of sub-sets of genes by itself or in conjunction with ATRA that have been shown to be modulated by ATRA in APL2. Keywords: other

2005-05-17 | GSE2668 | GEO

Proteome dynamics of HL-60, NB4, and K562 cells under the ATRA treatment

Project description:Searching for new strategies of acute myeloid leukemia (AML) treatment is of particular interest. Cell lines, e. g. HL-60 and NB4, represent model systems to study molecular features of leukemic cells. The all-trans-retinoic acid (ATRA) has proven itself to be an effective treatment for one of AML subtypes, i.e., acute promyelocytic leukemia (APL). At the same time, ATRA causes granulocytic differentiation of non-APL leukemic cells in vitro. Combination of new therapeutics with ATRA could improve efficiency of treatment. Studying the proteome perturbation in leukemic cells under the ATRA treatment allows to determine potential regulatory molecules that could be affected pharmacologically. Thus, the TMT-based proteomic profiles of HL-60, NB4, and K562 cell lines under the ATRA treatment were obtained at 0, 3, 12, 24, and 72 h after the ATRA treatment.

2024-06-23 | PXD050317 | Pride

Phase I Dose Escalation Study of ATRA Combined with the LSD1 inhibitor Tranylcypromine in AML and MDS

Project description:Preclinical studies have shown that combining the LSD1 inhibitor tranylcypromine (TCP) with all-trans retinoic acid (ATRA) induces differentiation and impairs survival in non-APL acute myeloid leukemia (AML). We conducted a Phase 1 clinical trial (NCT02273102) to evaluate the safety and preliminary activity of ATRA in combination with TCP in patients with relapsed/refractory AML and myelodysplasia (MDS). Seventeen patients (11 AML and 6 MDS) received ATRA-TCP therapy with ATRA (45 mg/m2 daily in divided doses) and TCP (3 dose levels: 10 mg twice-daily [BID], 20 mg BID, and 30 mg BID). ATRA-TCP had an acceptable safety profile. The maximum tolerated dose of TCP was 20 mg BID. There were 3 DLTs: dizziness (20 mg BID), asthenia (30 mg BID), and nausea/vomiting (30 mg BID). Best evaluable responses included 1 morphologic leukemia-free state (MLFS), 1 marrow complete remission (CR) with hematologic improvement, 2 stable disease with hematologic improvement, and 2 stable disease. In 13 response-evaluable patients, the overall response rate was 30.8% and clinical benefit rate 46.2%. Gene expression profiling of patient blasts showed that responding patients had a more dormant phenotype compared to non-responders at baseline. In human AML cell lines, we showed that treatment with ATRA-TCP increases differentiation capacity and/or cell death, and that ATRA-TCP regulates the in vitro expression of genes that segregate primary patients by their clinical response. These data indicate that LSD1 inhibition sensitizes AML cells to ATRA-induced differentiation and cell death and may restore clinical responsiveness in subsets of MDS and AML patients.

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Transcriptome dynamics of HL-60, NB4, and K562 cells under the ATRA treatment

Project description:Combination of new therapeutics with trans-retinoic acid (ATRA) could improve efficiency of acute myeloid leukemia (AML) treatment. Modeling the process of ATRA-induced differentiation based on transcriptomic profile of leukemic cells allows us to identify key molecules that could be affected to enhance the therapeutic effect of ATRA. Moreover, transcriptome analysis reveals the earliest steps of molecular response to inducer treatment. Thus, the transcriptomic profile of leukemic cells under the ATRA treatment at the different time points is considered as input data for further upstream regulator search.

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Project description:LC-MS/MS raw files of proteomics, phosphoproteomics and pTyr-proteomics from patients with high and low risk of adverse AML

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Palbociclib synergizes with ATRA to induce differentiation in AML

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Expression profiling of myeloid leukemia cell treated with vibsanine A, PMA and ATRA

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2016-02-28 | E-GEOD-78734 | biostudies-arrayexpress

Expression profiling of myeloid leukemia cell treated with vibsanin A, PMA and ATRA

Project description:All-trans retinoic acid (ATRA)-based differentiation therapy has achieved success with the treatment of acute promyelocytic leukemia (APL), a unique subtype of acute myeloid leukemia (AML). However, other subtypes of AML display resistance to ATRA-based treatment. Here, we demonstrate that a novel natural vibsane-type diterpenoid vibsanin A promotes the differentiation of myeloid leukemia cell lines and primary AML blasts. To reveal how vibsanin A function on promoting myeloid leukemia cell differentiation, we analyzed and compared the gene expression profiles in myeloid leukemia HL-60 cells treated with vibsanin A, PMA, and ATRA.

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