Maturation and apoptosis of primary human acute myeloblastic leukemia cells are determined by TNF-alpha exclusively through CD120A stimulation.
OBJECTIVE
Tumor necrosis factor-a plays an important role in hematopoiesis. Its effects are mediated through two membrane-bound receptors: TNF-R I (p55; CD 120a) and TNF-R II (p75; CD 120b). The aim of our study was to investigate the relative roles of these receptors.


METHODS
We analyzed in 16 acute myeloid leukemia cases whether TNF-alpha could induce in vitro maturation and apoptosis. We then investigated which of the two receptors was provoking monocytic maturation and which was responsible for apoptosis by using the agonistic MoAb HTR-9, directed at CD120a, and the CD120b antagonistic MoAb UTR-1.


RESULTS
Monocytic maturation (morphologic and immunologic) was induced in all cases studied, although to different rates, by TNF-alpha and by HTR-9 incubation. The addition of UTR-1 to TNF-alpha did not abolish maturation, nor did it affect apoptosis, which was present in primary AML cultures after 4 and 10 days.


CONCLUSIONS
We present here evidence that the sole stimulation of CD 120a, but not of CD120b, by TNF-alpha is responsible for bot monocytic maturation and apoptosis of primary AML blasts.
Santini
V
V
Dept. of Hematology, Policlinico di Careggi, viale Morgagni 85, 50134 Florence, Italy. santini@unifi.it
Gozzini
A
A
Scappini
B
B
Rossi Ferrini
P
P
D015703:Antigens, CD / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects*; D018845:CD11 Antigens; D002454:Cell Differentiation / Q000187:drug effects; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000473:pathology*; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology* / Q000627:therapeutic use
D015703:Antigens, CD; D018845:CD11 Antigens; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha