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High GPR56 surface expression correlates with a leukemic stem cell gene signature in CD34‐positive AML.

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Title: High GPR56 surface expression correlates with a leukemic stem cell gene signature in CD34‐positive AML.
Authors: Daga, Shruti1,2 (AUTHOR), Rosenberger, Angelika1,2 (AUTHOR), Quehenberger, Franz3 (AUTHOR), Krisper, Nina2 (AUTHOR), Prietl, Barbara2,4 (AUTHOR), Reinisch, Andreas1 (AUTHOR), Zebisch, Armin1 (AUTHOR), Sill, Heinz1 (AUTHOR), Wölfler, Albert1,2 (AUTHOR) albert.woelfler@medunigraz.at
Source: Cancer Medicine. Apr2019, Vol. 8 Issue 4, p1771-1778. 8p.
Subject Terms: *STEM cells, *ACUTE myeloid leukemia, *SURFACE analysis, *GENE expression, *DISEASE relapse
Abstract: Acute myeloid leukemia (AML) is driven by a minor fraction of leukemic stem cells (LSCs) whose persistence is considered being the primary cause of disease relapse. A detailed characterization of the surface immunophenotype of LSCs to discriminate them from bulk leukemic blasts may enable successful targeting of this population thereby improving patient outcomes in AML. To identify surface markers, which may reflect LSC activity at diagnosis, we performed a detailed analysis of 16 putative LSC markers in CD34/38 leukemic subcompartments of 150 diagnostic AML samples using multicolor flow cytometry. The most promising markers were then selected to determine a possible correlation of their expression with a recently published LSC gene signature. We found GPR56 and CLL‐1 to be the most prominently differently expressed surface markers in AML subcompartments. While GPR56 was highest expressed within the LSC‐enriched CD34+38− subcompartment as compared to CD34+38+ and CD34− leukemic bulk cells, CLL‐1 expression was lowest in CD34+38− leukemic cells and increased in CD34+38+ and CD34− blasts. Furthermore, high GPR56 surface expression in CD34+38− leukemic cells correlated with a recently published LSC gene expression signature and was associated with decreased overall survival in patients receiving intensive chemotherapy. In contrast, CLL‐1 expression correlated inversely with the LSC gene signature and was not informative on outcome. Our data strongly support GPR56 as a promising clinically relevant marker for identifying leukemic cells with LSC activity at diagnosis in CD34‐positive AML. [ABSTRACT FROM AUTHOR]
Copyright of Cancer Medicine is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: High GPR56 surface expression correlates with a leukemic stem cell gene signature in CD34‐positive AML.
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  Data: <searchLink fieldCode="AR" term="%22Daga%2C+Shruti%22">Daga, Shruti</searchLink><relatesTo>1,2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Rosenberger%2C+Angelika%22">Rosenberger, Angelika</searchLink><relatesTo>1,2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Quehenberger%2C+Franz%22">Quehenberger, Franz</searchLink><relatesTo>3</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Krisper%2C+Nina%22">Krisper, Nina</searchLink><relatesTo>2</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Prietl%2C+Barbara%22">Prietl, Barbara</searchLink><relatesTo>2,4</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Reinisch%2C+Andreas%22">Reinisch, Andreas</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Zebisch%2C+Armin%22">Zebisch, Armin</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Sill%2C+Heinz%22">Sill, Heinz</searchLink><relatesTo>1</relatesTo> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Wölfler%2C+Albert%22">Wölfler, Albert</searchLink><relatesTo>1,2</relatesTo> (AUTHOR)<i> albert.woelfler@medunigraz.at</i>
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  Data: <searchLink fieldCode="JN" term="%22Cancer+Medicine%22">Cancer Medicine</searchLink>. Apr2019, Vol. 8 Issue 4, p1771-1778. 8p.
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  Data: *<searchLink fieldCode="DE" term="%22STEM+cells%22">STEM cells</searchLink><br />*<searchLink fieldCode="DE" term="%22ACUTE+myeloid+leukemia%22">ACUTE myeloid leukemia</searchLink><br />*<searchLink fieldCode="DE" term="%22SURFACE+analysis%22">SURFACE analysis</searchLink><br />*<searchLink fieldCode="DE" term="%22GENE+expression%22">GENE expression</searchLink><br />*<searchLink fieldCode="DE" term="%22DISEASE+relapse%22">DISEASE relapse</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Acute myeloid leukemia (AML) is driven by a minor fraction of leukemic stem cells (LSCs) whose persistence is considered being the primary cause of disease relapse. A detailed characterization of the surface immunophenotype of LSCs to discriminate them from bulk leukemic blasts may enable successful targeting of this population thereby improving patient outcomes in AML. To identify surface markers, which may reflect LSC activity at diagnosis, we performed a detailed analysis of 16 putative LSC markers in CD34/38 leukemic subcompartments of 150 diagnostic AML samples using multicolor flow cytometry. The most promising markers were then selected to determine a possible correlation of their expression with a recently published LSC gene signature. We found GPR56 and CLL‐1 to be the most prominently differently expressed surface markers in AML subcompartments. While GPR56 was highest expressed within the LSC‐enriched CD34+38− subcompartment as compared to CD34+38+ and CD34− leukemic bulk cells, CLL‐1 expression was lowest in CD34+38− leukemic cells and increased in CD34+38+ and CD34− blasts. Furthermore, high GPR56 surface expression in CD34+38− leukemic cells correlated with a recently published LSC gene expression signature and was associated with decreased overall survival in patients receiving intensive chemotherapy. In contrast, CLL‐1 expression correlated inversely with the LSC gene signature and was not informative on outcome. Our data strongly support GPR56 as a promising clinically relevant marker for identifying leukemic cells with LSC activity at diagnosis in CD34‐positive AML. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Cancer Medicine is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1002/cam4.2053
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        Text: English
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        PageCount: 8
        StartPage: 1771
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      – SubjectFull: STEM cells
        Type: general
      – SubjectFull: ACUTE myeloid leukemia
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      – SubjectFull: SURFACE analysis
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      – SubjectFull: GENE expression
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      – SubjectFull: DISEASE relapse
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      – TitleFull: High GPR56 surface expression correlates with a leukemic stem cell gene signature in CD34‐positive AML.
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            – D: 01
              M: 04
              Text: Apr2019
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              Y: 2019
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