Phenotyping and Target Expression Profiling of CD34+/CD38− and CD34+/CD38+ Stem- and Progenitor cells in Acute Lymphoblastic Leukemia
Leukemic stem cells (LSCs) are an emerging target of curative anti-leukemia therapy. In acute lymphoblastic leukemia (ALL), LSCs frequently express CD34 and often lack CD38. However, little is known about markers and targets expressed in ALL LSCs. We have examined marker- and target expression profi...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2018-06-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558618300885 |
| _version_ | 1818340936601567232 |
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| author | Katharina Blatt Ingeborg Menzl Gregor Eisenwort Sabine Cerny-Reiterer Harald Herrmann Susanne Herndlhofer Gabriele Stefanzl Irina Sadovnik Daniela Berger Alexandra Keller Alexander Hauswirth Gregor Hoermann Michael Willmann Thomas Rülicke Heinz Sill Wolfgang R. Sperr Christine Mannhalter Junia V. Melo Ulrich Jäger Veronika Sexl Peter Valent |
| author_facet | Katharina Blatt Ingeborg Menzl Gregor Eisenwort Sabine Cerny-Reiterer Harald Herrmann Susanne Herndlhofer Gabriele Stefanzl Irina Sadovnik Daniela Berger Alexandra Keller Alexander Hauswirth Gregor Hoermann Michael Willmann Thomas Rülicke Heinz Sill Wolfgang R. Sperr Christine Mannhalter Junia V. Melo Ulrich Jäger Veronika Sexl Peter Valent |
| author_sort | Katharina Blatt |
| collection | DOAJ |
| description | Leukemic stem cells (LSCs) are an emerging target of curative anti-leukemia therapy. In acute lymphoblastic leukemia (ALL), LSCs frequently express CD34 and often lack CD38. However, little is known about markers and targets expressed in ALL LSCs. We have examined marker- and target expression profiles in CD34+/CD38− LSCs in patients with Ph+ ALL (n = 22) and Ph− ALL (n = 27) by multi-color flow cytometry and qPCR. ALL LSCs expressed CD19 (B4), CD44 (Pgp-1), CD123 (IL-3RA), and CD184 (CXCR4) in all patients tested. Moreover, in various subgroups of patients, LSCs also displayed CD20 (MS4A1) (10/41 = 24%), CD22 (12/20 = 60%), CD33 (Siglec-3) (20/48 = 42%), CD52 (CAMPATH-1) (17/40 = 43%), IL-1RAP (13/29 = 45%), and/or CD135 (FLT3) (4/20 = 20%). CD25 (IL-2RA) and CD26 (DPPIV) were expressed on LSCs in Ph+ ALL exhibiting BCR/ABL1p210, whereas in Ph+ ALL with BCR/ABL1p190, LSCs variably expressed CD25 but did not express CD26. In Ph− ALL, CD34+/CD38− LSCs expressed IL-1RAP in 6/18 patients (33%), but did not express CD25 or CD26. Normal stem cells stained negative for CD25, CD26 and IL-1RAP, and expressed only low amounts of CD52. In xenotransplantation experiments, CD34+/CD38− and CD34+/CD38+ cells engrafted NSG mice after 12–20 weeks, and targeting with antibodies against CD33 and CD52 resulted in reduced engraftment. Together, LSCs in Ph+ and Ph− ALL display unique marker- and target expression profiles. In Ph+ ALL with BCR/ABL1p210, the LSC-phenotype closely resembles the marker-profile of CD34+/CD38− LSCs in chronic myeloid leukemia, confirming the close biologic relationship of these neoplasms. Targeting of LSCs with specific antibodies or related immunotherapies may facilitate LSC eradication in ALL. |
| first_indexed | 2024-12-13T15:50:49Z |
| format | Article |
| id | doaj.art-1452d10d7e4546a986e7d94a5ac51778 |
| institution | Directory Open Access Journal |
| issn | 1476-5586 1522-8002 |
| language | English |
| last_indexed | 2024-12-13T15:50:49Z |
| publishDate | 2018-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-1452d10d7e4546a986e7d94a5ac517782022-12-21T23:39:29ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022018-06-0120663264210.1016/j.neo.2018.04.004Phenotyping and Target Expression Profiling of CD34+/CD38− and CD34+/CD38+ Stem- and Progenitor cells in Acute Lymphoblastic LeukemiaKatharina Blatt0Ingeborg Menzl1Gregor Eisenwort2Sabine Cerny-Reiterer3Harald Herrmann4Susanne Herndlhofer5Gabriele Stefanzl6Irina Sadovnik7Daniela Berger8Alexandra Keller9Alexander Hauswirth10Gregor Hoermann11Michael Willmann12Thomas Rülicke13Heinz Sill14Wolfgang R. Sperr15Christine Mannhalter16Junia V. Melo17Ulrich Jäger18Veronika Sexl19Peter Valent20Ludwig Boltzmann Cluster Oncology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, AustriaDepartment of Biomedical Science, Institute of Pharmacology and Toxicology, University of Veterinary Medicine Vienna, Veterinaerplatz 1, 1210 Vienna, AustriaLudwig Boltzmann Cluster Oncology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, AustriaLudwig Boltzmann Cluster Oncology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, AustriaLudwig Boltzmann Cluster Oncology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, AustriaLudwig Boltzmann Cluster Oncology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, AustriaDepartment of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, AustriaDepartment of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, AustriaDepartment of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, AustriaDepartment of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, AustriaLudwig Boltzmann Cluster Oncology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, AustriaLudwig Boltzmann Cluster Oncology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, AustriaLudwig Boltzmann Cluster Oncology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, AustriaInstitute of Laboratory Animal Science, University of Veterinary Medicine Vienna, Veterinaerplatz 1, 1210 Vienna, AustriaDepartment of Internal Medicine, Division of Hematology, Medical University of Graz, Auenbruggerplatz 2, 8036 Graz, AustriaLudwig Boltzmann Cluster Oncology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, AustriaDepartment of Laboratory Medicine, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, AustriaFaculty of Health and Medical Sciences, University of Adelaide, Adelaide, South Australia 5005, AustraliaLudwig Boltzmann Cluster Oncology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, AustriaDepartment of Biomedical Science, Institute of Pharmacology and Toxicology, University of Veterinary Medicine Vienna, Veterinaerplatz 1, 1210 Vienna, AustriaLudwig Boltzmann Cluster Oncology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, AustriaLeukemic stem cells (LSCs) are an emerging target of curative anti-leukemia therapy. In acute lymphoblastic leukemia (ALL), LSCs frequently express CD34 and often lack CD38. However, little is known about markers and targets expressed in ALL LSCs. We have examined marker- and target expression profiles in CD34+/CD38− LSCs in patients with Ph+ ALL (n = 22) and Ph− ALL (n = 27) by multi-color flow cytometry and qPCR. ALL LSCs expressed CD19 (B4), CD44 (Pgp-1), CD123 (IL-3RA), and CD184 (CXCR4) in all patients tested. Moreover, in various subgroups of patients, LSCs also displayed CD20 (MS4A1) (10/41 = 24%), CD22 (12/20 = 60%), CD33 (Siglec-3) (20/48 = 42%), CD52 (CAMPATH-1) (17/40 = 43%), IL-1RAP (13/29 = 45%), and/or CD135 (FLT3) (4/20 = 20%). CD25 (IL-2RA) and CD26 (DPPIV) were expressed on LSCs in Ph+ ALL exhibiting BCR/ABL1p210, whereas in Ph+ ALL with BCR/ABL1p190, LSCs variably expressed CD25 but did not express CD26. In Ph− ALL, CD34+/CD38− LSCs expressed IL-1RAP in 6/18 patients (33%), but did not express CD25 or CD26. Normal stem cells stained negative for CD25, CD26 and IL-1RAP, and expressed only low amounts of CD52. In xenotransplantation experiments, CD34+/CD38− and CD34+/CD38+ cells engrafted NSG mice after 12–20 weeks, and targeting with antibodies against CD33 and CD52 resulted in reduced engraftment. Together, LSCs in Ph+ and Ph− ALL display unique marker- and target expression profiles. In Ph+ ALL with BCR/ABL1p210, the LSC-phenotype closely resembles the marker-profile of CD34+/CD38− LSCs in chronic myeloid leukemia, confirming the close biologic relationship of these neoplasms. Targeting of LSCs with specific antibodies or related immunotherapies may facilitate LSC eradication in ALL.http://www.sciencedirect.com/science/article/pii/S1476558618300885 |
| spellingShingle | Katharina Blatt Ingeborg Menzl Gregor Eisenwort Sabine Cerny-Reiterer Harald Herrmann Susanne Herndlhofer Gabriele Stefanzl Irina Sadovnik Daniela Berger Alexandra Keller Alexander Hauswirth Gregor Hoermann Michael Willmann Thomas Rülicke Heinz Sill Wolfgang R. Sperr Christine Mannhalter Junia V. Melo Ulrich Jäger Veronika Sexl Peter Valent Phenotyping and Target Expression Profiling of CD34+/CD38− and CD34+/CD38+ Stem- and Progenitor cells in Acute Lymphoblastic Leukemia Neoplasia: An International Journal for Oncology Research |
| title | Phenotyping and Target Expression Profiling of CD34+/CD38− and CD34+/CD38+ Stem- and Progenitor cells in Acute Lymphoblastic Leukemia |
| title_full | Phenotyping and Target Expression Profiling of CD34+/CD38− and CD34+/CD38+ Stem- and Progenitor cells in Acute Lymphoblastic Leukemia |
| title_fullStr | Phenotyping and Target Expression Profiling of CD34+/CD38− and CD34+/CD38+ Stem- and Progenitor cells in Acute Lymphoblastic Leukemia |
| title_full_unstemmed | Phenotyping and Target Expression Profiling of CD34+/CD38− and CD34+/CD38+ Stem- and Progenitor cells in Acute Lymphoblastic Leukemia |
| title_short | Phenotyping and Target Expression Profiling of CD34+/CD38− and CD34+/CD38+ Stem- and Progenitor cells in Acute Lymphoblastic Leukemia |
| title_sort | phenotyping and target expression profiling of cd34 cd38 and cd34 cd38 stem and progenitor cells in acute lymphoblastic leukemia |
| url | http://www.sciencedirect.com/science/article/pii/S1476558618300885 |
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