Proteomic profiling identifies distinct protein patterns in acute myelogenous leukemia CD34+CD38- stem-like cells.

Acute myeloid leukemia (AML) is believed to arise from leukemic stem-like cells (LSC) making understanding the biological differences between LSC and normal stem cells (HSC) or common myeloid progenitors (CMP) crucial to understanding AML biology. To determine if protein expression patterns were dif...

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Autores principales: Steven M Kornblau, Amina Qutub, Hui Yao, Heather York, Yi Hua Qiu, David Graber, Farhad Ravandi, Jorge Cortes, Michael Andreeff, Nianxiang Zhang, Kevin R Coombes
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Publicado: Public Library of Science (PLoS) 2013
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spelling oai:doaj.org-article:38799d6c55234a568892bf62691729512021-11-18T08:49:33ZProteomic profiling identifies distinct protein patterns in acute myelogenous leukemia CD34+CD38- stem-like cells.1932-620310.1371/journal.pone.0078453https://doaj.org/article/38799d6c55234a568892bf62691729512013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24223100/?tool=EBIhttps://doaj.org/toc/1932-6203Acute myeloid leukemia (AML) is believed to arise from leukemic stem-like cells (LSC) making understanding the biological differences between LSC and normal stem cells (HSC) or common myeloid progenitors (CMP) crucial to understanding AML biology. To determine if protein expression patterns were different in LSC compared to other AML and CD34+ populations, we measured the expression of 121 proteins by Reverse Phase Protein Arrays (RPPA) in 5 purified fractions from AML marrow and blood samples: Bulk (CD3/CD19 depleted), CD34-, CD34+(CMP), CD34+CD38+ and CD34+CD38-(LSC). LSC protein expression differed markedly from Bulk (n =31 cases, 93/121 proteins) and CD34+ cells (n = 30 cases, 88/121 proteins) with 54 proteins being significantly different (31 higher, 23 lower) in LSC than in either Bulk or CD34+ cells. Sixty-seven proteins differed significantly between CD34+ and Bulk blasts (n = 69 cases). Protein expression patterns in LSC and CD34+ differed markedly from normal CD34+ cells. LSC were distinct from CD34+ and Bulk cells by principal component and by protein signaling network analysis which confirmed individual protein analysis. Potential targetable submodules in LSC included the proteins PU.1(SP1), P27, Mcl1, HIF1α, cMET, P53, Yap, and phospho-Stats 1, 5 and 6. Protein expression and activation in LSC differs markedly from other blast populations suggesting that studies of AML biology should be performed in LSC.Steven M KornblauAmina QutubHui YaoHeather YorkYi Hua QiuDavid GraberFarhad RavandiJorge CortesMichael AndreeffNianxiang ZhangKevin R CoombesPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 10, p e78453 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Steven M Kornblau
Amina Qutub
Hui Yao
Heather York
Yi Hua Qiu
David Graber
Farhad Ravandi
Jorge Cortes
Michael Andreeff
Nianxiang Zhang
Kevin R Coombes
Proteomic profiling identifies distinct protein patterns in acute myelogenous leukemia CD34+CD38- stem-like cells.
description Acute myeloid leukemia (AML) is believed to arise from leukemic stem-like cells (LSC) making understanding the biological differences between LSC and normal stem cells (HSC) or common myeloid progenitors (CMP) crucial to understanding AML biology. To determine if protein expression patterns were different in LSC compared to other AML and CD34+ populations, we measured the expression of 121 proteins by Reverse Phase Protein Arrays (RPPA) in 5 purified fractions from AML marrow and blood samples: Bulk (CD3/CD19 depleted), CD34-, CD34+(CMP), CD34+CD38+ and CD34+CD38-(LSC). LSC protein expression differed markedly from Bulk (n =31 cases, 93/121 proteins) and CD34+ cells (n = 30 cases, 88/121 proteins) with 54 proteins being significantly different (31 higher, 23 lower) in LSC than in either Bulk or CD34+ cells. Sixty-seven proteins differed significantly between CD34+ and Bulk blasts (n = 69 cases). Protein expression patterns in LSC and CD34+ differed markedly from normal CD34+ cells. LSC were distinct from CD34+ and Bulk cells by principal component and by protein signaling network analysis which confirmed individual protein analysis. Potential targetable submodules in LSC included the proteins PU.1(SP1), P27, Mcl1, HIF1α, cMET, P53, Yap, and phospho-Stats 1, 5 and 6. Protein expression and activation in LSC differs markedly from other blast populations suggesting that studies of AML biology should be performed in LSC.
format article
author Steven M Kornblau
Amina Qutub
Hui Yao
Heather York
Yi Hua Qiu
David Graber
Farhad Ravandi
Jorge Cortes
Michael Andreeff
Nianxiang Zhang
Kevin R Coombes
author_facet Steven M Kornblau
Amina Qutub
Hui Yao
Heather York
Yi Hua Qiu
David Graber
Farhad Ravandi
Jorge Cortes
Michael Andreeff
Nianxiang Zhang
Kevin R Coombes
author_sort Steven M Kornblau
title Proteomic profiling identifies distinct protein patterns in acute myelogenous leukemia CD34+CD38- stem-like cells.
title_short Proteomic profiling identifies distinct protein patterns in acute myelogenous leukemia CD34+CD38- stem-like cells.
title_full Proteomic profiling identifies distinct protein patterns in acute myelogenous leukemia CD34+CD38- stem-like cells.
title_fullStr Proteomic profiling identifies distinct protein patterns in acute myelogenous leukemia CD34+CD38- stem-like cells.
title_full_unstemmed Proteomic profiling identifies distinct protein patterns in acute myelogenous leukemia CD34+CD38- stem-like cells.
title_sort proteomic profiling identifies distinct protein patterns in acute myelogenous leukemia cd34+cd38- stem-like cells.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/38799d6c55234a568892bf6269172951
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