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Gene expression profiles of AML derived stem cells; similarity to hematopoietic stem cells
by
Rechavi, G
, Ein-Dor, L
, Domany, E
, Lapidot, T
, Amariglio, N
, Margalit, O
, Jacob-Hirsh, J
, Gal, H
, Trakhtenbrot, L
, Nagler, A
, Givol, D
, Tavor, S
, Avigdor, A
in
Acute myeloid leukemia
/ Biological and medical sciences
/ Biology
/ Cancer
/ Cancer Research
/ CD34 antigen
/ CD38 antigen
/ Cell cycle
/ Cell Cycle - genetics
/ Cell self-renewal
/ Chromosome aberrations
/ Critical Care Medicine
/ DNA microarrays
/ DNA repair
/ DNA Repair - genetics
/ Female
/ gamma-Aminobutyric Acid - analogs & derivatives
/ gamma-Aminobutyric Acid - pharmacology
/ Gene expression
/ Gene Expression Profiling
/ Genes
/ Hematologic and hematopoietic diseases
/ Hematology
/ Hematopoietic stem cells
/ Hematopoietic Stem Cells - metabolism
/ Humans
/ Intensive
/ Internal Medicine
/ Leukemia
/ Leukemia, Myeloid, Acute - drug therapy
/ Leukemia, Myeloid, Acute - metabolism
/ Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
/ Male
/ Medical prognosis
/ Medical sciences
/ Medicine
/ Medicine & Public Health
/ Mutation
/ Neoplastic Stem Cells - metabolism
/ Oncology
/ original-article
/ Progenitor cells
/ Proteinase inhibitors
/ Receptors, Notch - antagonists & inhibitors
/ Receptors, Notch - physiology
/ Secretase
/ Signal Transduction
/ Stem cells
/ Triglycerides - pharmacology
/ Tumors
2006
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Gene expression profiles of AML derived stem cells; similarity to hematopoietic stem cells
by
Rechavi, G
, Ein-Dor, L
, Domany, E
, Lapidot, T
, Amariglio, N
, Margalit, O
, Jacob-Hirsh, J
, Gal, H
, Trakhtenbrot, L
, Nagler, A
, Givol, D
, Tavor, S
, Avigdor, A
in
Acute myeloid leukemia
/ Biological and medical sciences
/ Biology
/ Cancer
/ Cancer Research
/ CD34 antigen
/ CD38 antigen
/ Cell cycle
/ Cell Cycle - genetics
/ Cell self-renewal
/ Chromosome aberrations
/ Critical Care Medicine
/ DNA microarrays
/ DNA repair
/ DNA Repair - genetics
/ Female
/ gamma-Aminobutyric Acid - analogs & derivatives
/ gamma-Aminobutyric Acid - pharmacology
/ Gene expression
/ Gene Expression Profiling
/ Genes
/ Hematologic and hematopoietic diseases
/ Hematology
/ Hematopoietic stem cells
/ Hematopoietic Stem Cells - metabolism
/ Humans
/ Intensive
/ Internal Medicine
/ Leukemia
/ Leukemia, Myeloid, Acute - drug therapy
/ Leukemia, Myeloid, Acute - metabolism
/ Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
/ Male
/ Medical prognosis
/ Medical sciences
/ Medicine
/ Medicine & Public Health
/ Mutation
/ Neoplastic Stem Cells - metabolism
/ Oncology
/ original-article
/ Progenitor cells
/ Proteinase inhibitors
/ Receptors, Notch - antagonists & inhibitors
/ Receptors, Notch - physiology
/ Secretase
/ Signal Transduction
/ Stem cells
/ Triglycerides - pharmacology
/ Tumors
2006
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Gene expression profiles of AML derived stem cells; similarity to hematopoietic stem cells
by
Rechavi, G
, Ein-Dor, L
, Domany, E
, Lapidot, T
, Amariglio, N
, Margalit, O
, Jacob-Hirsh, J
, Gal, H
, Trakhtenbrot, L
, Nagler, A
, Givol, D
, Tavor, S
, Avigdor, A
in
Acute myeloid leukemia
/ Biological and medical sciences
/ Biology
/ Cancer
/ Cancer Research
/ CD34 antigen
/ CD38 antigen
/ Cell cycle
/ Cell Cycle - genetics
/ Cell self-renewal
/ Chromosome aberrations
/ Critical Care Medicine
/ DNA microarrays
/ DNA repair
/ DNA Repair - genetics
/ Female
/ gamma-Aminobutyric Acid - analogs & derivatives
/ gamma-Aminobutyric Acid - pharmacology
/ Gene expression
/ Gene Expression Profiling
/ Genes
/ Hematologic and hematopoietic diseases
/ Hematology
/ Hematopoietic stem cells
/ Hematopoietic Stem Cells - metabolism
/ Humans
/ Intensive
/ Internal Medicine
/ Leukemia
/ Leukemia, Myeloid, Acute - drug therapy
/ Leukemia, Myeloid, Acute - metabolism
/ Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
/ Male
/ Medical prognosis
/ Medical sciences
/ Medicine
/ Medicine & Public Health
/ Mutation
/ Neoplastic Stem Cells - metabolism
/ Oncology
/ original-article
/ Progenitor cells
/ Proteinase inhibitors
/ Receptors, Notch - antagonists & inhibitors
/ Receptors, Notch - physiology
/ Secretase
/ Signal Transduction
/ Stem cells
/ Triglycerides - pharmacology
/ Tumors
2006
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Gene expression profiles of AML derived stem cells; similarity to hematopoietic stem cells
Journal Article
Gene expression profiles of AML derived stem cells; similarity to hematopoietic stem cells
2006
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Overview
Tumors contain a fraction of cancer stem cells that maintain the propagation of the disease. The CD34+CD38− cells, isolated from acute myeloid leukemia (AML), were shown to be enriched leukemic stem cells (LSC). We isolated the CD34+CD38− cell fraction from AML and compared their gene expression profiles to the CD34+CD38+ cell fraction, using microarrays. We found 409 genes that were at least twofold over- or underexpressed between the two cell populations. These include underexpression of DNA repair, signal transduction and cell cycle genes, consistent with the relative quiescence of stem cells, and chromosomal aberrations and mutations of leukemic cells. Comparison of the LSC expression data to that of normal hematopoietic stem cells (HSC) revealed that 34% of the modulated genes are shared by both LSC and HSC, supporting the suggestion that the LSC originated within the HSC progenitors. We focused on the Notch pathway since Jagged-2, a Notch ligand was found to be overexpressed in the LSC samples. We show that DAPT, an inhibitor of gamma-secretase, a protease that is involved in Jagged and Notch signaling, inhibits LSC growth in colony formation assays. Identification of additional genes that regulate LSC self-renewal may provide new targets for therapy.
Publisher
Nature Publishing Group UK,Nature Publishing,Nature Publishing Group
Subject
/ Biological and medical sciences
/ Biology
/ Cancer
/ Female
/ gamma-Aminobutyric Acid - analogs & derivatives
/ gamma-Aminobutyric Acid - pharmacology
/ Genes
/ Hematologic and hematopoietic diseases
/ Hematopoietic Stem Cells - metabolism
/ Humans
/ Leukemia
/ Leukemia, Myeloid, Acute - drug therapy
/ Leukemia, Myeloid, Acute - metabolism
/ Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis
/ Male
/ Medicine
/ Mutation
/ Neoplastic Stem Cells - metabolism
/ Oncology
/ Receptors, Notch - antagonists & inhibitors
/ Receptors, Notch - physiology
/ Triglycerides - pharmacology
/ Tumors
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