Hematopoietic stem cells express multiple myeloid markers: implications for the origin and targeted therapy of acute myeloid leukemia.
Human hematopoietic stem cells (HSCs) are generally regarded as being devoid of the markers expressed by differentiated blood cells, the lineage-specific antigens. However, recent work suggests that genes associated with the myeloid lineage are transcribed in mouse HSCs. Here, we explore whether myeloid genes are actually translated in human HSCs. We show that CD33, CD13, and CD123, well-established myeloid markers, are expressed on human long-term repopulating cells from cord blood and bone marrow. In addition, we demonstrate that nonobese diabetic/severe combined immunodeficiency (NOD/SCID) leukemia-initiating cells (SL-ICs) are restricted to the CD33+ fraction in 11 of 12 acute myeloid leukemia (AML) samples studied, indicating that leukemic stem cells (LSCs) express this antigen. This study changes our view of HSCs and the process of differentiation. Furthermore, based on the phenotypic similarity of HSCs and LSCs, our data provide support for the hypothesis that AML derives from an HSC. Our findings also provide a challenge to contemporary attempts to improve the outcome of AML using myeloid antigen-targeted therapies, given the potential for HSC killing.
Taussig
David C
DC
Haematopoietic Stem Cell Laboratory, Cancer Research UK, London Research Institute.
Pearce
Daniel J
DJ
Simpson
Catherine
C
Rohatiner
Ama Z
AZ
Lister
T Andrew
TA
Kelly
Gavin
G
Luongo
Jennifer L
JL
Danet-Desnoyers
Gwenn-Aël H
GA
Bonnet
Dominique
D
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D005312:Fetal Blood / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism* / Q000628:therapy*; D051379:Mice; D016513:Mice, SCID; D010641:Phenotype; D012680:Sensitivity and Specificity
D015703:Antigens, CD; D014408:Biomarkers, Tumor