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 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.

• Publication year

  2013

• Venue

  PLoS ONE

• Publication date

  2013-10-24

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1371/journal.pone.0078453PMID 24223100PMCID 3816767
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• What are stem cells?

  2021cited by this paper
• Surface Adjustment of Reverse Phase Protein Arrays using Positive Control Spots

  2012cited by this paper
• Network analysis of reverse phase protein expression data: Characterizing protein signatures in acute myeloid leukemia cytogenetic categories t(8;21) and inv(16)

  2012cited by this paper
• The hallmarks of cancer

  2012cited by this paper
• A clinically relevant population of leukemic CD34(+)CD38(-) cells in acute myeloid leukemia.

  2012cited by this paper
• Densely interconnected transcriptional circuits control cell states in human hematopoiesis.

  2011influential reference
• Stem cell gene expression programs influence clinical outcome in human leukemia

  2011cited by this paper
• Turning up the heat on colorectal cancer

  2011cited by this paper
• Leukemia stem cells and microenvironment: biology and therapeutic targeting.

  2011cited by this paper
• Targeting HIF1α eliminates cancer stem cells in hematological malignancies.

  2011cited by this paper
• Dynamic single cell network profiles in AML are associated with patient response to standard induction therapy Running Title: SCNP in AML Induction Therapy Response

  2010cited by this paper
• Identification of a small subpopulation of candidate leukemia initiating cells in the side population (SP) of patients with acute myeloid leukemia

  2010cited by this paper
• Dynamic Single-Cell Network Profiles in Acute Myelogenous Leukemia Are Associated with Patient Response to Standard Induction Therapy

  2010cited by this paper
• Persistent malignant stem cells in del(5q) myelodysplasia in remission.

  2010cited by this paper
• FLT3-ITD up-regulates MCL-1 to promote survival of stem cells in acute myeloid leukemia via FLT3-ITD–specific STAT5 activation

  2010cited by this paper
• Leukemia-initiating cells from some acute myeloid leukemia patients with mutated nucleophosmin reside in the CD34(-) fraction.

  2010cited by this paper
• Mass cytometry: technique for real time single cell multitarget immunoassay based on inductively coupled plasma time-of-flight mass spectrometry.

  2009cited by this paper
• Aldehyde dehydrogenase activity among primary leukemia cells is associated with stem cell features and correlates with adverse clinical outcomes.

  2009cited by this paper
• Integrating and annotating the interactome using the MiMI plugin for cytoscape

  2009cited by this paper
• Dysregulated gene expression networks in human acute myelogenous leukemia stem cells

  2009cited by this paper
• FLT3-ITD up-regulates MCL-1 to promote survival of stem cells in acute myeloid leukemia via FLT3-ITD-specific STAT5 activation.

  2009cited by this paper
• Functional proteomic profiling of AML predicts response and survival.

  2009cited by this paper
• Lyl1 and Scl Dosage Is Critical for Adult Hematopoietic Stem Cell Function and Survival

  2008cited by this paper
• Identification of a Small Subpopulation of Candidate Leukemia‐Initiating Cells in the Side Population of Patients with Acute Myeloid Leukemia

  2008cited by this paper
• Anti-CD38 antibody-mediated clearance of human repopulating cells masks the heterogeneity of leukemia-initiating cells.

  2008cited by this paper
• In childhood acute lymphoblastic leukemia, blasts at different stages of immunophenotypic maturation have stem cell properties.

  2008cited by this paper
• Leukemia stem cells in acute myeloid leukemia.

  2008cited by this paper
• Proteomic Profiling of 150 Proteins in 511 Acute Myelogenous Leukemia (AML) Patient Samples Using Reverse Phase Proteins Arrays (RPPA) Reveals Recurrent Proteins Expression Signatures with Prognostic Implications

  2008cited by this paper
• Non-parametric quantification of protein lysate arrays

  2007cited by this paper
• Tumor Growth Need Not Be Driven by Rare Cancer Stem Cells

  2007cited by this paper
• A distal single nucleotide polymorphism alters long-range regulation of the PU.1 gene in acute myeloid leukemia.

  2007cited by this paper
• Transcriptional dysregulation during myeloid transformation in AML

  2007cited by this paper
• Reverse phase protein array: validation of a novel proteomic technology and utility for analysis of primary leukemia specimens and hematopoietic stem cells

  2006cited by this paper
• Gene expression profiles of AML derived stem cells; similarity to hematopoietic stem cells

  2006cited by this paper
• Evaluation of clustering algorithms for protein-protein interaction networks

  2006cited by this paper
• Obligate Role of Anti-Apoptotic MCL-1 in the Survival of Hematopoietic Stem Cells

  2005cited by this paper
• High Stem Cell Frequency in Acute Myeloid Leukemia at Diagnosis Predicts High Minimal Residual Disease and Poor Survival

  2005cited by this paper
• Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1

  2004cited by this paper
• Simultaneous activation of multiple signal transduction pathways confers poor prognosis in acute myelogenous leukemia.

  2004cited by this paper
• Estimating the Occurrence of False Positives and False Negatives in Microarray Studies by Approximating and Partitioning the Empirical Distribution of P-values

  2003influential reference
• Gene expression analysis of purified hematopoietic stem cells and committed progenitors.

  2003cited by this paper
• An automated method for finding molecular complexes in large protein interaction networks

  2003cited by this paper
• CXCR4 chemokine receptors (CD184) and α4β1 integrins mediate spontaneous migration of human CD34+ progenitors and acute myeloid leukaemia cells beneath marrow stromal cells (pseudoemperipolesis)

  2003cited by this paper
• Comparing protein abundance and mRNA expression levels on a genomic scale

  2003cited by this paper
• Expression profiling of CD34+ hematopoietic stem/ progenitor cells reveals distinct subtypes of therapy-related acute myeloid leukemia

  2002cited by this paper
• Involvement and functional impairment of the CD34(+)CD38(-)Thy-1(+) hematopoietic stem cell pool in myelodysplastic syndromes with trisomy 8.

  2002cited by this paper
• Relating whole-genome expression data with protein-protein interactions.

  2002cited by this paper
• Bootstrapping cluster analysis: Assessing the reliability of conclusions from microarray experiments

  2001cited by this paper
• Modeling pO(2) distributions in the bone marrow hematopoietic compartment. I. Krogh's model.

  2001cited by this paper
• Modeling pO(2) distributions in the bone marrow hematopoietic compartment. II. Modified Kroghian models.

  2001cited by this paper
• The interleukin-3 receptor alpha chain is a unique marker for human acute myelogenous leukemia stem cells

  2000cited by this paper
• Primitive acute myeloid leukemia cells with long-term proliferative ability in vitro and in vivo lack surface expression of c-kit (CD117).

  2000cited by this paper
• Correlation between Protein and mRNA Abundance in Yeast

  1999cited by this paper
• Most acute myeloid leukemia progenitor cells with long-term proliferative ability in vitro and in vivo have the phenotype CD34(+)/CD71(-)/HLA-DR-.

  1998cited by this paper
• The chemokine receptor CXCR-4 is expressed on CD34+ hematopoietic progenitors and leukemic cells and mediates transendothelial migration induced by stromal cell-derived factor-1.

  1998cited by this paper
• Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell

  1997cited by this paper
• Characterization of a hierarchy in human acute myeloid leukemia progenitor cells.

  1996cited by this paper
• A cell initiating human acute myeloid leukaemia after transplantation into SCID mice

  1994cited by this paper
• Sequential generations of hematopoietic colonies derived from single nonlineage-committed CD34+CD38- progenitor cells.

  1991cited by this paper
• The architecture of bone marrow cell populations.

  1990cited by this paper

• Proteogenomic characterization of highly enriched viable leukemic blasts in acute myeloid leukemia: A SWOG report

  2024cites this paper
• System analysis of Huang-Lian-Jie-Du-Tang and their key active ingredients for overcoming CML resistance by suppression of leukemia stem cells.

  2023cites this paper
• Proteomic and phosphoproteomic landscapes of acute myeloid leukemia

  2022cites this paper
• Clinical relevance of proteomic profiling in de novo pediatric acute myeloid leukemia: a Children’s Oncology Group study

  2022cites this paper
• c-Myc plays a critical role in the antileukemic activity of the Mcl-1-selective inhibitor AZD5991 in acute myeloid leukemia

  2022cites this paper
• Proteomic Profiling Identifies Specific Leukemic Stem Cell-Associated Protein Expression Patterns in Pediatric AML Patients

  2022cites this paper
• Leukemic stem cell signatures in Acute myeloid leukemia- targeting the Guardians with novel approaches

  2022cites this paper
• Properties of Leukemic Stem Cells in Regulating Drug Resistance in Acute and Chronic Myeloid Leukemias

  2022cites this paper
• LGALS3 is connected to CD74 in a previously unknown protein network that is associated with poor survival in patients with AML

  2019cites this paper
• A quantitative analysis of heterogeneities and hallmarks in acute myelogenous leukaemia

  2019cites this paper
• Proteomic Profiling of Acute Promyelocytic Leukemia Identifies Two Protein Signatures Associated with Relapse

  2019cites this paper
• Phosphoproteomic Landscaping Identifies Non-canonical cKIT Signaling in Polycythemia Vera Erythroid Progenitors

  2019cites this paper
• Peptide microarray of pediatric acute myeloid leukemia is related to relapse and reveals involvement of DNA damage response and repair

  2019cites this paper
• Shining a light on cell signaling in leukemia through proteomics: relevance for the clinic

  2018cites this paper
• Proteomics in Acute Myeloid Leukemia Proteomics in Acute Myeloid Leukemia

  2018influential citation
• Recognition of Recurrent Protein Expression Patterns in Pediatric Acute Myeloid Leukemia Identified New Therapeutic Targets

  2018cites this paper
• TARGETING APOPTOTIC PATHWAYS TO OVERCOME DRUG RESISTANCE IN ACUTE MYELOID LEUKEMIA

  2017cites this paper
• The novel BMI-1 inhibitor PTC596 downregulates MCL-1 and induces p53-independent mitochondrial apoptosis in acute myeloid leukemia progenitor cells

  2017cites this paper
• Focal Adhesion Kinase as a Potential Target in AML and MDS

  2017cites this paper
• Prognostic impact of the CD34+/CD38− cell burden in patients with acute myeloid leukemia receiving allogeneic stem cell transplantation

  2017cites this paper
• Proteomic analysis of mitochondria: biological and clinical progresses in cancer

  2017cites this paper
• Proteomics in Acute Myeloid Leukemia

  2017cites this paper
• Serum proteomic spectral characteristics of acute myeloid leukemia and their clinical significance.

  2017cites this paper
• Phosphoproteomic profiling of mouse primary HSPCs reveals new regulators of HSPC mobilization.

  2016cites this paper
• Current attempts to implement siRNA-based RNAi in leukemia models.

  2016cites this paper
• Evidence that high-migration drug-surviving MOLT4 leukemia cells exhibit cancer stem cell-like properties.

  2016cites this paper
• New treatment strategies in myelodysplastic syndromes and acute myeloid leukemia: Hypomethylating agents and proteasome inhibitors

  2016cites this paper
• MicroRNA-9 promotes proliferation of leukemia cells in adult CD34-positive acute myeloid leukemia with normal karyotype by downregulation of Hes1

  2016cites this paper
• Effective targeting of primitive AML CD 34 + cells by the second-generation proteasome inhibitor carfilzomib C h ap ter 6

  2016cites this paper
• Alantolactone selectively ablates acute myeloid leukemia stem and progenitor cells

  2016cites this paper
• MLN0128, a novel mTOR kinase inhibitor, disrupts survival signaling and triggers apoptosis in AML and AML stem/ progenitor cells

  2016cites this paper
• Leukemic progenitor cells are susceptible to targeting by stimulated cytotoxic T cells against immunogenic leukemia‐associated antigens

  2015cites this paper
• Inhibition of Mcl-1 with the pan-Bcl-2 family inhibitor (-)BI97D6 overcomes ABT-737 resistance in acute myeloid leukemia.

  2015cites this paper
• Phosphorylation of GSK3α/β correlates with activation of AKT and is prognostic for poor overall survival in acute myeloid leukemia patients

  2015cites this paper
• The Use of “Omics” to Guide the Selection of Targeted Therapy

  2015cites this paper
• Implications of CXCR4/CXCL12 Interaction for Cancer Stem Cell Maintenance and Cancer Progression

  2015cites this paper
• Homéostasie cellulaire du fer dans les cellules leucémiques myéloïdes

  2015cites this paper
• Progress in RNAi-mediated Molecular Therapy of Acute and Chronic Myeloid Leukemia.

  2015cites this paper
• Single‐cell mass cytometry reveals intracellular survival/proliferative signaling in FLT3‐ITD‐mutated AML stem/progenitor cells

  2015cites this paper
• Global Cell Proteome Profiling, Phospho-signaling and Quantitative 
Proteomics for Identification of New Biomarkers in Acute Myeloid 
Leukemia Patients

  2015cites this paper
• Immunocapture strategies in translational proteomics

  2015cites this paper
• STAT transcription factors in normal and cancer stem cells.

  2014cites this paper
• STAT activation status differentiates leukemogenic from non-leukemogenic stem cells in AML and is suppressed by arsenic in t(6;9)-positive AML

  2014cites this paper
• Biomarkers to assess the efficiency of treatment with platinum-based drugs: what can metallomics add?

  2014cites this paper
• Capillary nano-immunoassay for Akt 1/2/3 and 4EBP1 phosphorylation in acute myeloid leukemia

  2014cites this paper
• AKT-induced reactive oxygen species generate imatinib-resistant clones emerging from chronic myeloid leukemia progenitor cells

  2014cites this paper