PMID- 29772458
OWN - NLM
STAT- MEDLINE
DCOM- 20181126
LR  - 20181126
IS  - 1476-5586 (Electronic)
IS  - 1522-8002 (Print)
IS  - 1476-5586 (Linking)
VI  - 20
IP  - 6
DP  - 2018 Jun
TI  - Phenotyping and Target Expression Profiling of CD34(+)/CD38(-) and 
      CD34(+)/CD38(+) Stem- and Progenitor cells in Acute Lymphoblastic Leukemia.
PG  - 632-642
LID - S1476-5586(18)30088-5 [pii]
LID - 10.1016/j.neo.2018.04.004 [doi]
AB  - 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/ABL1(p210), whereas in Ph(+) ALL with BCR/ABL1(p190), 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/ABL1(p210), 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.
CI  - Copyright (c) 2018 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Blatt, Katharina
AU  - Blatt K
AD  - Ludwig Boltzmann Cluster Oncology, Medical University of Vienna, Waehringer 
      Guertel 18-20, 1090 Vienna, Austria; Department of Internal Medicine I, Division 
      of Hematology and Hemostaseology, Medical University of Vienna, Waehringer 
      Guertel 18-20, 1090 Vienna, Austria.
FAU - Menzl, Ingeborg
AU  - Menzl I
AD  - Department of Biomedical Science, Institute of Pharmacology and Toxicology, 
      University of Veterinary Medicine Vienna, Veterinaerplatz 1, 1210 Vienna, 
      Austria.
FAU - Eisenwort, Gregor
AU  - Eisenwort G
AD  - Ludwig Boltzmann Cluster Oncology, Medical University of Vienna, Waehringer 
      Guertel 18-20, 1090 Vienna, Austria; Department of Internal Medicine I, Division 
      of Hematology and Hemostaseology, Medical University of Vienna, Waehringer 
      Guertel 18-20, 1090 Vienna, Austria.
FAU - Cerny-Reiterer, Sabine
AU  - Cerny-Reiterer S
AD  - Ludwig Boltzmann Cluster Oncology, Medical University of Vienna, Waehringer 
      Guertel 18-20, 1090 Vienna, Austria; Department of Internal Medicine I, Division 
      of Hematology and Hemostaseology, Medical University of Vienna, Waehringer 
      Guertel 18-20, 1090 Vienna, Austria.
FAU - Herrmann, Harald
AU  - Herrmann H
AD  - Ludwig Boltzmann Cluster Oncology, Medical University of Vienna, Waehringer 
      Guertel 18-20, 1090 Vienna, Austria; Department of Internal Medicine I, Division 
      of Hematology and Hemostaseology, Medical University of Vienna, Waehringer 
      Guertel 18-20, 1090 Vienna, Austria; Department of Radiotherapy, Medical 
      University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
FAU - Herndlhofer, Susanne
AU  - Herndlhofer S
AD  - Ludwig Boltzmann Cluster Oncology, Medical University of Vienna, Waehringer 
      Guertel 18-20, 1090 Vienna, Austria; Department of Internal Medicine I, Division 
      of Hematology and Hemostaseology, Medical University of Vienna, Waehringer 
      Guertel 18-20, 1090 Vienna, Austria.
FAU - Stefanzl, Gabriele
AU  - Stefanzl G
AD  - Department of Internal Medicine I, Division of Hematology and Hemostaseology, 
      Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
FAU - Sadovnik, Irina
AU  - Sadovnik I
AD  - Department of Internal Medicine I, Division of Hematology and Hemostaseology, 
      Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
FAU - Berger, Daniela
AU  - Berger D
AD  - Department of Internal Medicine I, Division of Hematology and Hemostaseology, 
      Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
FAU - Keller, Alexandra
AU  - Keller A
AD  - Department of Internal Medicine I, Division of Hematology and Hemostaseology, 
      Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
FAU - Hauswirth, Alexander
AU  - Hauswirth A
AD  - Ludwig Boltzmann Cluster Oncology, Medical University of Vienna, Waehringer 
      Guertel 18-20, 1090 Vienna, Austria; Department of Internal Medicine I, Division 
      of Hematology and Hemostaseology, Medical University of Vienna, Waehringer 
      Guertel 18-20, 1090 Vienna, Austria.
FAU - Hoermann, Gregor
AU  - Hoermann G
AD  - Ludwig Boltzmann Cluster Oncology, Medical University of Vienna, Waehringer 
      Guertel 18-20, 1090 Vienna, Austria; Department of Laboratory Medicine, Medical 
      University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
FAU - Willmann, Michael
AU  - Willmann M
AD  - Ludwig Boltzmann Cluster Oncology, Medical University of Vienna, Waehringer 
      Guertel 18-20, 1090 Vienna, Austria; Department/Clinic for Companion Animals and 
      Horses, Clinic for Small Animals, Clinical Unit of Internal Medicine, University 
      of Veterinary Medicine Vienna, Veterinaerplatz 1, 1210 Vienna, Austria.
FAU - Rulicke, Thomas
AU  - Rulicke T
AD  - Institute of Laboratory Animal Science, University of Veterinary Medicine Vienna, 
      Veterinaerplatz 1, 1210 Vienna, Austria.
FAU - Sill, Heinz
AU  - Sill H
AD  - Department of Internal Medicine, Division of Hematology, Medical University of 
      Graz, Auenbruggerplatz 2, 8036 Graz, Austria.
FAU - Sperr, Wolfgang R
AU  - Sperr WR
AD  - Ludwig Boltzmann Cluster Oncology, Medical University of Vienna, Waehringer 
      Guertel 18-20, 1090 Vienna, Austria; Department of Internal Medicine I, Division 
      of Hematology and Hemostaseology, Medical University of Vienna, Waehringer 
      Guertel 18-20, 1090 Vienna, Austria.
FAU - Mannhalter, Christine
AU  - Mannhalter C
AD  - Department of Laboratory Medicine, Medical University of Vienna, Waehringer 
      Guertel 18-20, 1090 Vienna, Austria.
FAU - Melo, Junia V
AU  - Melo JV
AD  - Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, South 
      Australia 5005, Australia; Department of Haematology, Imperial College London, 
      Kensington, London SW7 2AZ, United Kingdom.
FAU - Jager, Ulrich
AU  - Jager U
AD  - Ludwig Boltzmann Cluster Oncology, Medical University of Vienna, Waehringer 
      Guertel 18-20, 1090 Vienna, Austria; Department of Internal Medicine I, Division 
      of Hematology and Hemostaseology, Medical University of Vienna, Waehringer 
      Guertel 18-20, 1090 Vienna, Austria.
FAU - Sexl, Veronika
AU  - Sexl V
AD  - Department of Biomedical Science, Institute of Pharmacology and Toxicology, 
      University of Veterinary Medicine Vienna, Veterinaerplatz 1, 1210 Vienna, 
      Austria.
FAU - Valent, Peter
AU  - Valent P
AD  - Ludwig Boltzmann Cluster Oncology, Medical University of Vienna, Waehringer 
      Guertel 18-20, 1090 Vienna, Austria; Department of Internal Medicine I, Division 
      of Hematology and Hemostaseology, Medical University of Vienna, Waehringer 
      Guertel 18-20, 1090 Vienna, Austria. Electronic address: 
      peter.valent@meduniwien.ac.at.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180515
PL  - United States
TA  - Neoplasia
JT  - Neoplasia (New York, N.Y.)
JID - 100886622
RN  - 0 (Antigens, CD34)
RN  - 0 (Biomarkers, Tumor)
RN  - EC 3.2.2.6 (ADP-ribosyl Cyclase 1)
SB  - IM
MH  - ADP-ribosyl Cyclase 1/*metabolism
MH  - Animals
MH  - Antigens, CD34/*metabolism
MH  - Biomarkers, Tumor/metabolism
MH  - Cell Line
MH  - Female
MH  - Gene Expression Regulation, Leukemic/physiology
MH  - Humans
MH  - Leukemia, Myelogenous, Chronic, BCR-ABL Positive/metabolism
MH  - Leukemia, Myeloid, Acute/*metabolism
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Neoplastic Stem Cells/*metabolism
MH  - Stem Cells/*metabolism
PMC - PMC5994777
EDAT- 2018/05/18 06:00
MHDA- 2018/11/27 06:00
PMCR- 2018/05/15
CRDT- 2018/05/18 06:00
PHST- 2018/02/08 00:00 [received]
PHST- 2018/04/12 00:00 [revised]
PHST- 2018/04/13 00:00 [accepted]
PHST- 2018/05/18 06:00 [pubmed]
PHST- 2018/11/27 06:00 [medline]
PHST- 2018/05/18 06:00 [entrez]
PHST- 2018/05/15 00:00 [pmc-release]
AID - S1476-5586(18)30088-5 [pii]
AID - 10.1016/j.neo.2018.04.004 [doi]
PST - ppublish
SO  - Neoplasia. 2018 Jun;20(6):632-642. doi: 10.1016/j.neo.2018.04.004. Epub 2018 May 
      15.