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PXD031916-1

PXD031916 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleEarly response evaluation by single cell signaling profiling in acute myeloid leukemia
DescriptionBackground: A fundamental hallmark of cancer cells is their ability to sustain proliferative signaling and cell survival, reflected in a cellular chemotherapy response that is poorly understood. We questioned whether chemotherapy modulated phospho-signaling at 4 and 24 h in vivo could provide information about long-term survival in acute myeloid leukemia (AML), and if the signaling response to therapy was more informative than analysis at time of diagnosis. Methods: Peripheral blood was collected from 32 younger AML patients (age 16-74 years), before, 4- and 24 hours after start of induction chemotherapy. Samples were analyzed by 36-dimensional mass cytometry for assessment of alterations in immunophenotypes and intracellular signaling using unsupervised and supervised machine learning approaches. Results were validated by RNA sequencing and mass spectrometry proteomics (Super SILAC). Targeted sequencing was used to characterize patient samples for recurrent AML mutations. Drug sensitivity and resistance testing ex vivo was compared to activation of relevant signal transduction pathways and mutational profile. Findings: 5-year patient survival was accurately predicted in the leukemic cell population at 24 hours after therapy onset by phospho-proteins p-ERK1/2 (T202/Y204) and p-p38 (T180/Y182). RNA sequencing showed induction of MAPK target gene expression and the AP-1 transcription complex in patients with high p-ERK1/2. Super-SILAC proteomics confirmed an increase in the abundance of p38 prime target MAPKAPK2(MK2) 24 hours after start of induction therapy. Ex vivo drug sensitivity testing demonstrated high sensitivity to MEK inhibitors in the patient cells with high p-ERK1/2 measured at diagnosis or 24 hours after start of chemotherapy. Interpretation: Early single cell signaling response to chemotherapy provided precise prognostic information independent of stratification by genetics. We propose that early functional measurement of chemotherapy-potentiated MAPK pathway signaling could identify non-responders to intensive chemotherapy allowing precise treatment adjustment.
HostingRepositoryPRIDE
AnnounceDate2022-10-26
AnnouncementXMLSubmission_2022-10-26_06:33:37.151.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterEvenBirkeland
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListiodoacetamide derivatized residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-02-28 01:30:56ID requested
12022-10-26 06:33:37announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: AML, ERK, single cell
Contact List
Bjørn ToreGjertsen
contact affiliationCentre for Cancer Biomarkers (CCBIO), Department of Clinical Science, University of Bergen, Bergen, Norway. 2Department of Medicine, Hematology Section, Haukeland University Hospital, Helse Bergen HF, Bergen, Norway
contact emailBjorn.Gjertsen@uib.no
lab head
EvenBirkeland
contact affiliationInstitute of biomedicine, University of BErgen
contact emaileven.birkeland@uib.no
dataset submitter
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