Cytosine arabinoside does not cause differentiation in vitro of CFU-GM in marrow from normal, myelodysplastic or ANLL subjects.
This study examines the effect of cytosine arabinoside (Ara-C) on CFU-GM progenitor cells grown in methylcellulose culture from normal and myelodysplastic subjects and patients with acute non-lymphoblastic leukaemia. Light density marrow cells were incubated during culture with Ara-C concentrations ranging from 10(-4) M to 10(-12) M. After counting, colonies were cytospun and cells within the colonies examined for alkaline phosphatase positivity and expression of HLA-DR antigen, as indices of differentiation. Monocytes/macrophages were also enumerated in colonies using the monoclonal antibody CD14. In all subjects, 10(-4) M to 10(-6) M Ara-C caused significant reduction in CFU-GM colony formation compared with control (no Ara-C). In no instance did colony numbers increase. Ara-C across the dose curve had no effect on myeloid differentiation markers in any of the groups studied. Similarly, percentages of CD14 positive cells in colonies were not altered by exposure to Ara-C. Using this clonogenic model, these data suggest that Ara-C does not induce differentiation of CFU-GM stem cells in normal subjects or patients with myelodysplasia/acute non lymphoblastic leukemia.
Smith
M A
MA
Department of Haematology, Royal United Hospital, Combe Park, Bath, U.K.
Taylor
P C
PC
Smith
J G
JG
D000469:Alkaline Phosphatase / Q000032:analysis; D001853:Bone Marrow / Q000473:pathology; D001854:Bone Marrow Cells; D002454:Cell Differentiation / Q000187:drug effects; D003561:Cytarabine / Q000494:pharmacology*; D006098:Granulocytes / Q000166:cytology / Q000187:drug effects*; D006684:HLA-DR Antigens / Q000032:analysis; D006651:Histocytochemistry; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D015470:Leukemia, Myeloid, Acute / Q000473:pathology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects*; D009190:Myelodysplastic Syndromes / Q000473:pathology*; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects*
D006684:HLA-DR Antigens; D003561:Cytarabine; D000469:Alkaline Phosphatase