Constitutive expression and abnormal glycosylation of transferrin receptor in acute T-cell leukemia.
The expression of transferrin receptors (TrfRs) was investigated in acute T-cell leukemia (T-ALL) blasts at the molecular, biochemical, immunological, and functional level. TrfRs, although not detected on quiescent T-cells from normal adults, are constitutively expressed at high level on the blasts from all T-ALL patients and bind normally to transferrin. Their number is modulated by the intracellular iron level, but is independent of exogenous interleukin 2. They also exhibit immunological and biochemical abnormalities, in that: (a) they react preferentially with monoclonal antibodies (MAb) that recognize ligand-binding domains of TrfR (42/6 and 43/31), as compared to MAbs (B3/25, OKT9) that interact with the nonligand binding domains; (b) they have a reduced molecular weight, as compared to TrfR on normal thymocytes and activated T-lymphocytes: this phenomenon is apparently related to a defective glycosylation. It is noteworthy that expression of TrfR was not observed in a large series of other types of acute leukemias, i.e., pre-B, B, and myeloid leukemias, excluding erythroleukemias. The constitutive, high level expression of TrfRs on T-ALL blasts may play a key role in the stepwise progression of this malignancy and particularly provide a proliferative advantage to T-ALL blasts as compared to normal T-lymphocytes. Furthermore, indirect evidence suggests that the glycosylation defect of TrfR on T-ALL blasts contributes to their tumorigenic capacity.
Petrini
M
M
Department of Hematology-Oncology, Istituto Superiore di Sanità, Rome, Italy.
Pelosi-Testa
E
E
Sposi
N M
NM
Mastroberardino
G
G
Camagna
A
A
Bottero
L
L
Mavilio
F
F
Testa
U
U
Peschle
C
C
D000911:Antibodies, Monoclonal / Q000276:immunology; D015152:Blotting, Northern; D004591:Electrophoresis, Polyacrylamide Gel; D006031:Glycosylation; D006801:Humans; D007501:Iron / Q000494:pharmacology; D007502:Iron Chelating Agents / Q000494:pharmacology; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D011990:Receptors, Transferrin / Q000187:drug effects / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D007502:Iron Chelating Agents; D012333:RNA, Messenger; D011990:Receptors, Transferrin; D007501:Iron