TY - JOUR
T1 - Relationship between CD34/CD38 and side population (SP) defined leukemia stem cell compartments in acute myeloid leukemia
AU - Moshaver, Bijan
AU - Wouters, Rolf F.
AU - Kelder, Angèle
AU - Ossenkoppele, Gert J.
AU - Westra, Guus A. H.
AU - Kwidama, Zinia
AU - Rutten, Arjo R.
AU - Kaspers, Gert J. L.
AU - Zweegman, Sonja
AU - Cloos, Jacqueline
AU - Schuurhuis, Gerrit J.
PY - 2019
Y1 - 2019
N2 - Leukemic stem cells (LSCs), defined by CD34/CD38 expression, are believed to be essential for leukemia initiation and therapy resistance in acute myeloid leukemia. In addition, the side population (SP), characterized by high Hoechst 33342 efflux, reflecting therapy resistance, has leukemia initiating ability. The purpose of this study is, in both CD34-positive and CD34-negative AML, to integrate both types of LSC compartment into a new more restricted definition. Different CD34/CD38/SP defined putative LSC and normal hematopoietic compartments, with neoplastic or normal nature, respectively, were thus identified after cell sorting, and confirmed by FISH/PCR. Stem cell activity was assessed in the long-term liquid culture stem cell assay. SP fractions harbored the strongest functional stem cell activity in both normal and neoplastic cells in both CD34-positive and CD34-negative AML. Overall, inclusion of SP fraction decreased the size of the putative CD34/CD38 defined LSC compartment by a factor >500. For example, for the important CD34+CD38- LSC compartment, the median SP/CD34+CD38- frequency was 5.1 per million WBC (CD34-positive AML), and median SP/CD34-CD38+ frequency (CD34-negative AML) was 1796 per million WBC. Improved detection of LSC may enable identification of therapy resistant clones, and thereby identification of novel LSC specific, HSC sparing, therapies.
AB - Leukemic stem cells (LSCs), defined by CD34/CD38 expression, are believed to be essential for leukemia initiation and therapy resistance in acute myeloid leukemia. In addition, the side population (SP), characterized by high Hoechst 33342 efflux, reflecting therapy resistance, has leukemia initiating ability. The purpose of this study is, in both CD34-positive and CD34-negative AML, to integrate both types of LSC compartment into a new more restricted definition. Different CD34/CD38/SP defined putative LSC and normal hematopoietic compartments, with neoplastic or normal nature, respectively, were thus identified after cell sorting, and confirmed by FISH/PCR. Stem cell activity was assessed in the long-term liquid culture stem cell assay. SP fractions harbored the strongest functional stem cell activity in both normal and neoplastic cells in both CD34-positive and CD34-negative AML. Overall, inclusion of SP fraction decreased the size of the putative CD34/CD38 defined LSC compartment by a factor >500. For example, for the important CD34+CD38- LSC compartment, the median SP/CD34+CD38- frequency was 5.1 per million WBC (CD34-positive AML), and median SP/CD34-CD38+ frequency (CD34-negative AML) was 1796 per million WBC. Improved detection of LSC may enable identification of therapy resistant clones, and thereby identification of novel LSC specific, HSC sparing, therapies.
KW - AML
KW - CD34+CD38-
KW - Flowcytometry
KW - Leukemia stem cell
KW - Side population (SP)
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85064251553&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/31002948
U2 - https://doi.org/10.1016/j.leukres.2019.04.004
DO - https://doi.org/10.1016/j.leukres.2019.04.004
M3 - Article
C2 - 31002948
SN - 0145-2126
VL - 81
SP - 27
EP - 34
JO - Leukemia research
JF - Leukemia research
ER -