Zeitschriftenaufsatz
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2020
Delineation of target expression profiles in CD34+/CD38- and CD34+/CD38+ stem and progenitor cells in AML and CML
Autor:in
Hermann, Harald; Sadovnik, Irina; Eisenwort, Gregor; Ruelicke, Thomas; Blatt, Katharina; Herndlhofer, Susanne; Willman, Michael; Stefanzl, G.; Baumgartner, Sigrid; Greiner, G.; Schulenburg, Axel; Mueller, Niklas; Rabitsch, Werner; Bilban, Martin; Hoermann, Gregor; Streube, Berthold; Vallera, DA; Sperr, Wolfgang R.; Valent, Peter
Publikationen als Autor:in / Herausgeber:in der Vetmeduni
Journal
Abstrakt
In an attempt to identify novel markers and immunological targets in leukemic stem cells (LSCs) in acute myeloid leukemia (AML) and chronic myeloid leukemia (CML), we screened bone marrow (BM) samples from patients with AML (n = 274) or CML (n = 97) and controls (n = 288) for expression of cell membrane antigens on CD34(+)/CD38(-) and CD34(+)/CD38(+) cells by multicolor flow cytometry. In addition, we established messenger RNA expression profiles in purified sorted CD34(+)/CD38(-) and CD34(+)/CD38(+) cells using gene array and quantitative polymerase chain reaction. Aberrantly expressed markers were identified in all cohorts. In CML, CD34(+)/CD38(-) LSCs exhibited an almost invariable aberration profile, defined as CD25(+)/CD26(+)/CD56(+)/CD93(+)/IL-1RAP(+). By contrast, in patients with AML, CD34(+)/CD38(-) cells variably expressed "aberrant" membrane antigens, including CD25 (48%), CD96 (40%), CD371 (CLL-1; 68%), and IL-1RAP (65%). With the exception of a subgroup of FLT3 internal tandem duplication-mutated patients, AML LSCs did not exhibit CD26. All other surface markers and target antigens detected on AML and/or CML LSCs, including CD33, CD44, CD47, CD52, CD105, CD114, CD117, CD133, CD135, CD184, and roundabout-4, were also found on normal BM stem cells. However, several of these surface targets, including CD25, CD33, and CD123, were expressed at higher levels on CD34(+)/CD38(-) LSCs comparedwith normal BMstem cells. Moreover, antibody-mediated immunological targeting through CD33 or CD52 resulted in LSC depletion in vitro and a substantially reduced LSC engraftment in NOD.Cg-Prkdc(scid) Il2rg(tm1Wjl)/SzJ (NSG) mice. Together, we have established surface marker and target expression profiles of AML LSCs and CML LSCs, which should facilitate LSC enrichment, diagnostic LSC phenotyping, and development of LSC-eradicating immunotherapies.
Schlagwörter
ADP-ribosyl Cyclase 1genetics; Animals; Antigens, CD34; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positivegenetics; Leukemia, Myeloid, Acutegenetics; Mice; Mice, Inbred NOD; Neoplastic Stem Cells
Dokumententyp
Originalarbeit
ISSN/eISSN
2473-9529 - 2473-9537
10.1182/bloodadvances.2020001742
WoS ID
PubMed ID