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Phenotypic Characterization of Leukemia-Initiating Stem Cells in Chronic Myelomonocytic Leukemia
Chronic myelomonocytic leukemia (CMML) is a stem cell-derived neoplasm characterized by dysplasia, uncontrolled expansion of monocytes and a substantial risk to transform to secondary acute myeloid leukemia (sAML). So far, little is known about CMML-initiating cells. We found that leukemic stem cell...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611912/ https://www.ncbi.nlm.nih.gov/pubmed/33785864 http://dx.doi.org/10.1038/s41375-021-01227-z |
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author | Eisenwort, Gregor Sadovnik, Irina Keller, Alexandra Ivanov, Daniel Peter, Barbara Berger, Daniela Stefanzl, Gabriele Bauer, Karin Slavnitsch, Katharina Greiner, Georg Gleixner, Karoline V. Sperr, Wolfgang R. Willmann, Michael Sill, Heinz Bettelheim, Peter Geissler, Klaus Deininger, Michael Rülicke, Thomas Valent, Peter |
author_facet | Eisenwort, Gregor Sadovnik, Irina Keller, Alexandra Ivanov, Daniel Peter, Barbara Berger, Daniela Stefanzl, Gabriele Bauer, Karin Slavnitsch, Katharina Greiner, Georg Gleixner, Karoline V. Sperr, Wolfgang R. Willmann, Michael Sill, Heinz Bettelheim, Peter Geissler, Klaus Deininger, Michael Rülicke, Thomas Valent, Peter |
author_sort | Eisenwort, Gregor |
collection | PubMed |
description | Chronic myelomonocytic leukemia (CMML) is a stem cell-derived neoplasm characterized by dysplasia, uncontrolled expansion of monocytes and a substantial risk to transform to secondary acute myeloid leukemia (sAML). So far, little is known about CMML-initiating cells. We found that leukemic stem cells (LSC) in CMML reside in a CD34(+)/CD38(–) fraction of the malignant clone. Whereas CD34(+)/CD38(–) cells engrafted NSGS mice with overt CMML, no CMML was produced by CD34(+)/CD38(+) progenitors or the bulk of CD34(–) monocytes. CMML LSC invariably expressed CD33, CD117, CD123 and CD133. In a subset of patients, CMML LSC also displayed CD52, IL-1RAP and/or CLL-1. CMML LSC did not express CD25 or CD26. However, in sAML following CMML, the LSC also expressed CD25 and high levels of CD114, CD123 and IL-1RAP. No correlations between LSC phenotypes, CMML-variant, mutation-profiles, or clinical course were identified. Pre-incubation of CMML LSC with gemtuzumab-ozogamicin or venetoclax resulted in decreased growth and impaired engraftment in NSGS mice. Together, CMML LSC are CD34(+)/CD38(–) cells that express a distinct profile of surface markers and target-antigens. During progression to sAML, LSC acquire or upregulate certain cytokine receptors, including CD25, CD114 and CD123. Characterization of CMML LSC should facilitate their enrichment and the development of LSC-eradicating therapies. |
format | Online Article Text |
id | pubmed-7611912 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
record_format | MEDLINE/PubMed |
spelling | pubmed-76119122021-11-01 Phenotypic Characterization of Leukemia-Initiating Stem Cells in Chronic Myelomonocytic Leukemia Eisenwort, Gregor Sadovnik, Irina Keller, Alexandra Ivanov, Daniel Peter, Barbara Berger, Daniela Stefanzl, Gabriele Bauer, Karin Slavnitsch, Katharina Greiner, Georg Gleixner, Karoline V. Sperr, Wolfgang R. Willmann, Michael Sill, Heinz Bettelheim, Peter Geissler, Klaus Deininger, Michael Rülicke, Thomas Valent, Peter Leukemia Article Chronic myelomonocytic leukemia (CMML) is a stem cell-derived neoplasm characterized by dysplasia, uncontrolled expansion of monocytes and a substantial risk to transform to secondary acute myeloid leukemia (sAML). So far, little is known about CMML-initiating cells. We found that leukemic stem cells (LSC) in CMML reside in a CD34(+)/CD38(–) fraction of the malignant clone. Whereas CD34(+)/CD38(–) cells engrafted NSGS mice with overt CMML, no CMML was produced by CD34(+)/CD38(+) progenitors or the bulk of CD34(–) monocytes. CMML LSC invariably expressed CD33, CD117, CD123 and CD133. In a subset of patients, CMML LSC also displayed CD52, IL-1RAP and/or CLL-1. CMML LSC did not express CD25 or CD26. However, in sAML following CMML, the LSC also expressed CD25 and high levels of CD114, CD123 and IL-1RAP. No correlations between LSC phenotypes, CMML-variant, mutation-profiles, or clinical course were identified. Pre-incubation of CMML LSC with gemtuzumab-ozogamicin or venetoclax resulted in decreased growth and impaired engraftment in NSGS mice. Together, CMML LSC are CD34(+)/CD38(–) cells that express a distinct profile of surface markers and target-antigens. During progression to sAML, LSC acquire or upregulate certain cytokine receptors, including CD25, CD114 and CD123. Characterization of CMML LSC should facilitate their enrichment and the development of LSC-eradicating therapies. 2021-11-01 2021-03-30 /pmc/articles/PMC7611912/ /pubmed/33785864 http://dx.doi.org/10.1038/s41375-021-01227-z Text en http://www.nature.com/authors/editorial_policies/license.html#termsUsers may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Eisenwort, Gregor Sadovnik, Irina Keller, Alexandra Ivanov, Daniel Peter, Barbara Berger, Daniela Stefanzl, Gabriele Bauer, Karin Slavnitsch, Katharina Greiner, Georg Gleixner, Karoline V. Sperr, Wolfgang R. Willmann, Michael Sill, Heinz Bettelheim, Peter Geissler, Klaus Deininger, Michael Rülicke, Thomas Valent, Peter Phenotypic Characterization of Leukemia-Initiating Stem Cells in Chronic Myelomonocytic Leukemia |
title | Phenotypic Characterization of Leukemia-Initiating Stem Cells in Chronic Myelomonocytic Leukemia |
title_full | Phenotypic Characterization of Leukemia-Initiating Stem Cells in Chronic Myelomonocytic Leukemia |
title_fullStr | Phenotypic Characterization of Leukemia-Initiating Stem Cells in Chronic Myelomonocytic Leukemia |
title_full_unstemmed | Phenotypic Characterization of Leukemia-Initiating Stem Cells in Chronic Myelomonocytic Leukemia |
title_short | Phenotypic Characterization of Leukemia-Initiating Stem Cells in Chronic Myelomonocytic Leukemia |
title_sort | phenotypic characterization of leukemia-initiating stem cells in chronic myelomonocytic leukemia |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611912/ https://www.ncbi.nlm.nih.gov/pubmed/33785864 http://dx.doi.org/10.1038/s41375-021-01227-z |
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