The Progression of Acute Myeloid Leukemia from First Diagnosis to Chemoresistant Relapse: A Comparison of Proteomic and Phosphoproteomic Profiles

Cancers
Elise AasebøMaria Hernandez-Valladares

Abstract

Acute myeloid leukemia (AML) is an aggressive hematological malignancy. Nearly 50% of the patients who receive the most intensive treatment develop chemoresistant leukemia relapse. Although the leukemogenic events leading to relapse seem to differ between patients (i.e., regrowth from a clone detected at first diagnosis, progression from the original leukemic or preleukemic stem cells), a common characteristic of relapsed AML is increased chemoresistance. The aim of the present study was to investigate at the proteomic level whether leukemic cells from relapsed patients present overlapping molecular mechanisms that contribute to this chemoresistance. We used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to compare the proteomic and phosphoproteomic profiles of AML cells derived from seven patients at the time of first diagnosis and at first relapse. At the time of first relapse, AML cells were characterized by increased levels of proteins important for various mitochondrial functions, such as mitochondrial ribosomal subunit proteins (MRPL21, MRPS37) and proteins for RNA processing (DHX37, RNA helicase; RPP40, ribonuclease P component), DNA repair (ERCC3, DNA repair factor IIH helicase; GTF2F1, general transcription ...Continue Reading

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Citations

Sep 23, 2020·International Journal of Molecular Sciences·Maria Hernandez-ValladaresFrode Selheim
Nov 27, 2020·International Journal of Molecular Sciences·Guomin HuangHong Zhang
Aug 28, 2021·Journal of Personalized Medicine·Ida Sofie GrønningsæterKimberley Joanne Hatfield

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Datasets Mentioned

BETA
PXD018359

Methods Mentioned

BETA
flow cytometry
density gradient separation

Software Mentioned

Cytoscape
Image J
iceLogo
KSEA App
ClusterONE
Perseus
MaxQuant
GraphPad Prism
SILAC

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