Clonal Heterogeneity Reflected by PI3K-AKT-mTOR Signaling in Human Acute Myeloid Leukemia Cells and Its Association with Adverse Prognosis

Cancers
Ina NepstadO Bruserud

Abstract

Clonal heterogeneity detected by karyotyping is a biomarker associated with adverse prognosis in acute myeloid leukemia (AML). Constitutive activation of the phosphatidylinositol-3-kinase-Akt-mechanistic target of rapamycin (PI3K-Akt-mTOR) pathway is present in AML cells, and this pathway integrates signaling from several upstream receptors/mediators. We suggest that this pathway reflects biologically important clonal heterogeneity. We investigated constitutive PI3K-Akt-mTOR pathway activation in primary human AML cells derived from 114 patients, together with 18 pathway mediators. The cohort included patients with normal karyotype or single karyotype abnormalities and with an expected heterogeneity of molecular genetic abnormalities. Clonal heterogeneity reflected as pathway mediator heterogeneity was detected for 49 patients. Global gene expression profiles of AML cell populations with and without clonal heterogeneity differed with regard to expression of ectopic olfactory receptors (a subset of G-protein coupled receptors) and proteins involved in G-protein coupled receptor signaling. Finally, the presence of clonal heterogeneity was associated with adverse prognosis for patients receiving intensive antileukemic treatment. T...Continue Reading

References

Aug 20, 2002·Journal of Hematotherapy & Stem Cell Research·Bjørn Tore GjertsenØystein Bruserud
Sep 18, 2007·Nature·Andreas KellerHiroaki Matsunami
Jan 10, 2009·Nature Protocols·Da Wei HuangRichard A Lempicki
Apr 25, 2009·The Journal of Biological Chemistry·Eva M NeuhausHanns Hatt
Sep 26, 2013·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Tilmann BochtlerAlwin Krämer
Dec 17, 2014·Archives of Biochemistry and Biophysics·Désirée MaßbergHanns Hatt
Sep 17, 2015·The New England Journal of Medicine·Hartmut DöhnerClara D Bloomfield
Feb 11, 2016·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Rena MoritaNoriyuki Sato
Mar 2, 2016·Methods in Cell Biology·Gabriela Antunes, Fabio Marques Simoes de Souza
May 27, 2016·Proteomics. Clinical Applications·Mercedes Lachén-MontesEnrique Santamaría
Jun 9, 2016·The New England Journal of Medicine·Elli PapaemmanuilPeter J Campbell
Jul 28, 2016·Frontiers in Aging Neuroscience·Isidro FerrerStefano Gustincich
Aug 26, 2016·The Journal of Comparative Neurology·James E SchwobJulie Hewitt Coleman
May 12, 2017·Wellcome Open Research·Marco RanzaniDavid J Adams
May 24, 2017·Drug Discovery Today·Barbara PavanAlessandro Dalpiaz
May 26, 2017·Expert Opinion on Therapeutic Targets·Yoko TabeMarina Konopleva
Dec 26, 2017·Blood Reviews·Lauren Herschbein, Jane L Liesveld
Jun 14, 2018·Physiological Reviews·Désirée Maßberg, Hanns Hatt

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Citations

Feb 7, 2020·International Journal of Environmental Research and Public Health·Yunqiu PuYuepu Pu
Mar 21, 2020·Cancers·Elise AasebøMaria Hernandez-Valladares
Apr 25, 2020·International Journal of Molecular Sciences·Ina NepstadHåkon Reikvam
Sep 23, 2020·International Journal of Molecular Sciences·Maria Hernandez-ValladaresFrode Selheim
Mar 19, 2021·Frontiers in Cell and Developmental Biology·Dong-Hu YuXiao-Lan Ruan
Aug 18, 2021·Neoplasia : an International Journal for Oncology Research·Afsar Ali MianEl-Nasir M A Lalani
Aug 25, 2021·Scientific Reports·Can YueYiming Luo

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Methods Mentioned

BETA
flow cytometry
on flow
density gradient separation

Software Mentioned

Statistical Package for the Social Sciences ( SPSS )
DAVID Bioinformatics Resources
FlowJo
Express
GenomeStudio

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