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Prospective separation of normal and leukemic stem cells based on differential expression of TIM3, a human acute myeloid leukemia stem cell marker

Hematopoietic tissues in acute myeloid leukemia (AML) patients contain both leukemia stem cells (LSC) and residual normal hematopoietic stem cells (HSC). The ability to prospectively separate residual HSC from LSC would enable important scientific and clinical investigation including the possibility... Full description

Journal Title: Proceedings of the National Academy of Sciences of the United States of America 22 March 2011, Vol.108(12), pp.5009-14
Main Author: Jan, Max
Other Authors: Chao, Mark P , Cha, Adriel C , Alizadeh, Ash A , Gentles, Andrew J , Weissman, Irving L , Majeti, Ravindra
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: E-ISSN: 1091-6490 ; PMID: 21383193 Version:1 ; DOI: 10.1073/pnas.1100551108
Link: http://pubmed.gov/21383193
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recordid: medline21383193
title: Prospective separation of normal and leukemic stem cells based on differential expression of TIM3, a human acute myeloid leukemia stem cell marker
format: Article
creator:
  • Jan, Max
  • Chao, Mark P
  • Cha, Adriel C
  • Alizadeh, Ash A
  • Gentles, Andrew J
  • Weissman, Irving L
  • Majeti, Ravindra
subjects:
  • Gene Expression Regulation, Leukemic
  • Neoplastic Stem Cells
  • Biomarkers, Tumor -- Biosynthesis
  • Cell Separation -- Methods
  • Leukemia, Myeloid, Acute -- Metabolism
  • Membrane Proteins -- Biosynthesis
ispartof: Proceedings of the National Academy of Sciences of the United States of America, 22 March 2011, Vol.108(12), pp.5009-14
description: Hematopoietic tissues in acute myeloid leukemia (AML) patients contain both leukemia stem cells (LSC) and residual normal hematopoietic stem cells (HSC). The ability to prospectively separate residual HSC from LSC would enable important scientific and clinical investigation including the possibility of purged autologous hematopoietic cell transplants. We report here the identification of TIM3 as an AML stem cell surface marker more highly expressed on multiple specimens of AML LSC than on normal bone marrow HSC. TIM3 expression was detected in all cytogenetic subgroups of AML, but was significantly higher in AML-associated with core binding factor translocations or mutations in CEBPA. By assessing engraftment in NOD/SCID/IL2Rγ-null mice, we determined that HSC function resides predominantly in the TIM3-negative fraction of normal bone marrow, whereas LSC function from multiple AML specimens resides predominantly in the TIM3-positive compartment. Significantly, differential TIM3 expression enabled the prospective separation of HSC from LSC in the majority of AML specimens with detectable residual HSC function.
language: eng
source:
identifier: E-ISSN: 1091-6490 ; PMID: 21383193 Version:1 ; DOI: 10.1073/pnas.1100551108
fulltext: fulltext
issn:
  • 10916490
  • 1091-6490
url: Link


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titleProspective separation of normal and leukemic stem cells based on differential expression of TIM3, a human acute myeloid leukemia stem cell marker
creatorJan, Max ; Chao, Mark P ; Cha, Adriel C ; Alizadeh, Ash A ; Gentles, Andrew J ; Weissman, Irving L ; Majeti, Ravindra
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subjectGene Expression Regulation, Leukemic ; Neoplastic Stem Cells ; Biomarkers, Tumor -- Biosynthesis ; Cell Separation -- Methods ; Leukemia, Myeloid, Acute -- Metabolism ; Membrane Proteins -- Biosynthesis
descriptionHematopoietic tissues in acute myeloid leukemia (AML) patients contain both leukemia stem cells (LSC) and residual normal hematopoietic stem cells (HSC). The ability to prospectively separate residual HSC from LSC would enable important scientific and clinical investigation including the possibility of purged autologous hematopoietic cell transplants. We report here the identification of TIM3 as an AML stem cell surface marker more highly expressed on multiple specimens of AML LSC than on normal bone marrow HSC. TIM3 expression was detected in all cytogenetic subgroups of AML, but was significantly higher in AML-associated with core binding factor translocations or mutations in CEBPA. By assessing engraftment in NOD/SCID/IL2Rγ-null mice, we determined that HSC function resides predominantly in the TIM3-negative fraction of normal bone marrow, whereas LSC function from multiple AML specimens resides predominantly in the TIM3-positive compartment. Significantly, differential TIM3 expression enabled the prospective separation of HSC from LSC in the majority of AML specimens with detectable residual HSC function.
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titleProspective separation of normal and leukemic stem cells based on differential expression of TIM3, a human acute myeloid leukemia stem cell marker
descriptionHematopoietic tissues in acute myeloid leukemia (AML) patients contain both leukemia stem cells (LSC) and residual normal hematopoietic stem cells (HSC). The ability to prospectively separate residual HSC from LSC would enable important scientific and clinical investigation including the possibility of purged autologous hematopoietic cell transplants. We report here the identification of TIM3 as an AML stem cell surface marker more highly expressed on multiple specimens of AML LSC than on normal bone marrow HSC. TIM3 expression was detected in all cytogenetic subgroups of AML, but was significantly higher in AML-associated with core binding factor translocations or mutations in CEBPA. By assessing engraftment in NOD/SCID/IL2Rγ-null mice, we determined that HSC function resides predominantly in the TIM3-negative fraction of normal bone marrow, whereas LSC function from multiple AML specimens resides predominantly in the TIM3-positive compartment. Significantly, differential TIM3 expression enabled the prospective separation of HSC from LSC in the majority of AML specimens with detectable residual HSC function.
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titleProspective separation of normal and leukemic stem cells based on differential expression of TIM3, a human acute myeloid leukemia stem cell marker
authorJan, Max ; Chao, Mark P ; Cha, Adriel C ; Alizadeh, Ash A ; Gentles, Andrew J ; Weissman, Irving L ; Majeti, Ravindra
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abstractHematopoietic tissues in acute myeloid leukemia (AML) patients contain both leukemia stem cells (LSC) and residual normal hematopoietic stem cells (HSC). The ability to prospectively separate residual HSC from LSC would enable important scientific and clinical investigation including the possibility of purged autologous hematopoietic cell transplants. We report here the identification of TIM3 as an AML stem cell surface marker more highly expressed on multiple specimens of AML LSC than on normal bone marrow HSC. TIM3 expression was detected in all cytogenetic subgroups of AML, but was significantly higher in AML-associated with core binding factor translocations or mutations in CEBPA. By assessing engraftment in NOD/SCID/IL2Rγ-null mice, we determined that HSC function resides predominantly in the TIM3-negative fraction of normal bone marrow, whereas LSC function from multiple AML specimens resides predominantly in the TIM3-positive compartment. Significantly, differential TIM3 expression enabled the prospective separation of HSC from LSC in the majority of AML specimens with detectable residual HSC function.
doi10.1073/pnas.1100551108
pmid21383193
issn00278424
oafree_for_read
date2011-03-22