Abstract
Background: Acute myeloblastic leukemia (AML) can be viewed as newly formed, abnormal hemopoeitic tissue initiated by few leukemic stem cells (LSCs). Recognizing the LSC and identifying their behavior, plays a pivotal role in the approach of a targeted therapy.Colony-stimulating factor 1 (CSF-1), also known as M-CSF, is a protein ligand that acts on the CSF1R promotes mononuclear phagocytes survival, proliferation and differentiation.
Aim of the work: Defining the self-renewing [Thy1-, CD34+, CD38-] LICs in AML cases before and after induction chemotherapy as a predictor for relapse and to determine how CSF1R (Fms) and CD34 markers affect the growth and survival of human leukemic cells in the CD38- Thy1- population.
Patients and methods: This study was carried out on 30 samples from the peripheral blood of adult patients with de-novo acute myeloid leukemia. The majority of the patients were monocytic AML
Samples were sorted into four populations (Fms+CD34-, Fms+CD34+, Fms-CD34+ and Fms-CD34-) according to the surface markers of the cells. Cells were cultured on mouse stromal cells transfected with a plasmid containing human CSF-1. Samples were cultured using Iscove's modified Dulbecc's medium (IMDM).The cultures were assessed for survival of leukemic cells in days.
Results: The mean survival in days of the cells was 13.9 before chemotherapy and 14.1 after chemotherapy. The difference in growth was insignificant (p>0.05). The Fms-CD34+ population in all but two samples tested had the longest survival time in culture.
Conclusion: Our results suggest that leukemic stem cells may survive chemotherapy mainly due to their quiescence.
Human CSF-1 was shown to increase the number of leukemic cells in co-culture with mouse stroma after 5 weeks. A novel leukemic stem cell (Fms-CD34+) has been identified and is the cell responsible for the growth and maintenance of the leukemic bulk.
No relevant conflicts of interest to declare.
Author notes
Asterisk with author names denotes non-ASH members.
