Phenotyping and target expression profiling of CD34+/CD38- and CD34+/CD38+ stem- and progenitor cells in acute lymphoblastic leukemia
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
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.
Date Issued
2018-06-01
Date Acceptance
2018-04-13
Citation
Neoplasia, 2018, 20 (6), pp.632-642
ISSN
0212-9787
Publisher
Ediciones Doyma S.A.
Start Page
632
End Page
642
Journal / Book Title
Neoplasia
Volume
20
Issue
6
Copyright Statement
© 2018 The Authors. Published by Elsevier Inc. on behalf of Neoplasia Press, Inc.
This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/
)
This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/
)
Sponsor
Imperial College Trust
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/29772458
PII: S1476-5586(18)30088-5
Grant Number
PC3532ICT
Subjects
1103 Clinical Sciences
Oncology & Carcinogenesis
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2018-05-15