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MiRNAs expression profiling in circulating lymphocytes of CML patients after imatinib discontinuation

ABSTRACT: Some chronic myeloid leukemia (CML) patients with complete molecular response (CMR) are considered able to sustain the CMR after imatinib discontinuation (STOP-IM). Mahon et al. reported that among patients with a CMR lasting at least 2 consecutive years, the CMR was sustained in 41% after imatinib discontinuation. To more appropriately identify patients who can safely discontinue imatinib, we assessed the miRNA profiles of CML patients. We compared CML patients who sustained CMR for more than 6 months after discontinuation of imatinib (STOP-IM group) with those who were receiving imatinib with CMR (currently called as UMD: undetermined minimal disease), and with healthy volunteers (controls).

ORGANISM(S): Homo sapiens

PROVIDER: GSE47652 | GEO | 2014/05/15

SECONDARY ACCESSION(S): PRJNA207034

REPOSITORIES: GEO

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miRNAs expression profiling in circulating lymphocytes of CML patients after imatinib discontinuation

Project description:Some chronic myeloid leukemia (CML) patients with complete molecular response (CMR) are considered able to sustain the CMR after imatinib discontinuation (STOP-IM). Mahon et al. reported that among patients with a CMR lasting at least 2 consecutive years, the CMR was sustained in 41% after imatinib discontinuation. To more appropriately identify patients who can safely discontinue imatinib, we assessed the miRNA profiles of CML patients. We compared CML patients who sustained CMR for more than 6 months after discontinuation of imatinib (STOP-IM group) with those who were receiving imatinib with CMR (currently called as UMD: undetermined minimal disease), and with healthy volunteers (controls). Peripheral blood mononuclear cells (PBMCs) were harvested form 10ml of whole blood. Isolation of total RNA was performed using the mirVana PARIS kit (Ambion, Austin, TX, USA). The expression profile of miRNAs was determined using the Human Taqman miRNA Arrays A (Applied Biosystems). RNU6B were used as acontrol. QRT-PCR was carried out on an Applied Biosystems 7900HT thermal cycler using the manufacturerM-bM-^@M-^Ys recommended program. Finally, all the raw data from each array was run on Data Assist Software ver.3.1 (Applied Biosystems).

2014-05-15 | E-GEOD-47652 | biostudies-arrayexpress

Expression profiling in extracellular miRNAs (plasma miRNAs) of CML patients after imatinib discontinuation (STOP-IM)

2016-03-31 | GSE75391 | GEO

Expression profiling in extracellular miRNAs (exosomal miRNAs) of CML patients after imatinib discontinuation (STOP-IM)

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Expression profiling in extracellular miRNAs (plasma miRNAs) of CML patients after imatinib discontinuation (STOP-IM)

Project description:An approximately 40% of chronic myeloid leukemia (CML) patients who discontinued imatinib (IM) therapy maintained undetectable minimal residual disease (UMRD) for more than one year (STOP-IM). We set out to examine plasma miRNAs expression in CML patients who could discontinue IM, to seek the possible distinguishable biomarker in STOP-IM CML patients. We compared CML patients who sustained UMRD for more than one year after discontinuation of imatinib (STOP-IM group) with healthy volunteers (controls). In 7 patients who had discontinued IM with sustained UMRD for more than 6 months (STOP-IM group), samples were collected when IM was stopped. Seven healthy volunteers served as control. Plasma samples were harvested form 2ml of whole blood. Isolation of total RNA was performed using the mirVana PARIS kit (Ambion, Austin, TX, USA). The expression profile of miRNAs was determined using the Human Taqman miRNA Arrays A (Applied Biosystems). Synthetic ath-miR-159 (Hokkaido System Science, Hokkaido, Japan) were used as a control. QRT-PCR was carried out on an Applied Biosystems 7900HT thermal cycler using the manufacturerâ??s recommended program. With the use of SDS2.2 software and Data Assist (Thermo Fisher Sciences), the expression of plasma miRNAs was calculated based on cycle threshold (Ct) values normalized by those of ath-miR-159, which was spiked in each plasma sample. Data analysis was done using GeneSiferâ?? software (Perkin Elmer, Waltham, MA, USA). The Benjamini-Hochberg algorithm was used for estimation of false discovery rates.

2016-03-31 | E-GEOD-75391 | biostudies-arrayexpress

Expression profiling in extracellular miRNAs (exosomal miRNAs) of CML patients after imatinib discontinuation (STOP-IM)

Project description:An approximately 40% of chronic myeloid leukemia (CML) patients who discontinued imatinib (IM) therapy maintained undetectable minimal residual disease (UMRD) for more than one year (STOP-IM). We therefore set out to examine exosomal miRNAs expression in CML patients who could discontinue IM, to seek the possible distinguishable biomarker in STOP-IM CML patients. We compared CML patients who sustained UMRD for more than one year after discontinuation of imatinib (STOP-IM group) with healthy volunteers (controls). In 7 patients who had discontinued IM with sustained UMRD for more than 6 months (STOP-IM group), samples were collected when IM was stopped. Seven healthy volunteers served as control. Plasma samples were harvested form 2ml of whole blood. Exosoms were isolated from plasma using a Total exosome isolation kit for plasma (Life Technologies). Isolation of total RNA was performed using the mirVana PARIS kit (Ambion, Austin, TX, USA). The expression profile of miRNAs was determined using the Human Taqman miRNA Arrays A (Applied Biosystems). Synthetic ath-miR-159 (Hokkaido System Science, Hokkaido, Japan) were used as a control. QRT-PCR was carried out on an Applied Biosystems 7900HT thermal cycler using the manufacturerâs recommended program. With the use of SDS2.2 software and Data Assist (Thermo Fisher Sciences), the expression of plasma miRNAs was calculated based on cycle threshold (Ct) values normalized by those of ath-miR-159, which was spiked in each plasma sample. Data analysis was done using GeneSiferâ software (Perkin Elmer, Waltham, MA, USA). The Benjamini-Hochberg algorithm was used for estimation of false discovery rates.

2016-03-31 | E-GEOD-75389 | biostudies-arrayexpress

Expression profiling in exosomal miRNAs of CML patients with musculoskeletal pain associated with discontinuation of Imatinib

Project description:An approximately 60% of chronic myeloid leukemia (CML) patients who achieved a deep molecular response for more than 2 years maintained a major molecular response after discontinuation of imatinib. These findings indicate the possibility that a portion of CML patients treated with Tyrosine kinase inhibitors (TKIs) could discontinue TKI therapy, although long-term prognosis and/or adverse events after TKIs cessation remain unclear. Recent reports showed that transient musculoskeletal pain occurs in approximately 30% of CML patients after stopping imatinib. To ascertain the factors underlying musculoskeletal events after TKI cessation, we investigated exosomal miRNA in five CML patients who did not experience musculoskeletal events and five patients with musculoskeletal pain after stopping TKIs.

2016-12-15 | GSE85903 | GEO

Expression profiling in extracellular miRNAs of CML patients after imatinib discontinuation (STOP-IM)

Project description:Expression profiling in extracellular miRNAs of CML patients after imatinib discontinuation (STOP-IM)

| PRJNA304101 | ENA

Homo sapiens

Project description:Expression profiling in extracellular miRNAs (exosomal miRNAs) of CML patients after imatinib discontinuation (STOP-IM)

| PRJNA304103 | ENA

Homo sapiens

Project description:Expression profiling in extracellular miRNAs (plasma miRNAs) of CML patients after imatinib discontinuation (STOP-IM)

| PRJNA304102 | ENA

Quantitative proteomic analysis of plasma exosomes to identify the candidate biomarker of Imatinib Resistance in Chronic Myeloid Leukemia patients

Project description:Imatinib (IM), a tyrosine kinase inhibitor (TKI), has markedly improved the survival and life quality of chronic myeloid leukemia (CML) patients. However, the lack of speciﬁc biomarkers for IM resistance remains a serious clinical challenge. Recently, growing evidence has suggested that exosome-harbored proteins were involved in tumor drug resistance and could be novel biomarkers for the diagnosis and drug sensitivity prediction of cancer. Therefore, we aimed to investigate the proteomic proﬁle of plasma exosomes derived from CML patients to identify ideal biomarkers for IM resistance. We extracted exosomes from pooled plasma samples of 9 imatinib-resistant CML patients and 9 imatinib-sensitive CML patients by ultracentrifugation. Then, we identified the expression levels of exosomal proteins by liquid chromatography-tandem mass spectrometry (LC-MS/MS) based label free quantification. Bioinformatics analyses were used to analyze the proteomic data. we found that RPL13 and RPL14 exhibited exceptional upregulation in imatinib-resistant CML patients, which were further confirmed by PRM and WB. Proteomic analysis of plasma exosomes provides new ideas and important information for the study of IM resistance in CML. Especially the exosomal proteins (RPL13 and RPL14), which may have great potential as biomarkers of IM resistance.

2022-02-16 | PXD028779 | Pride

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