Proliferation response of leukemic cells to CD70 ligation oscillates with recurrent remission and relapse in a low-grade lymphoma.
Interactions of the TNF-related cell surface ligand CD70 with its receptor CD27 provide a costimulatory signal in B and T cell activation. Functional CD70-CD27 interactions could contribute to lymphoma and leukemia progression. This possibility was studied using DNA microarrays on a unique case of low-grade lymphoma/leukemia characterized by recurrent cycles of acute leukemic phase alternating with spontaneous remission. Upon induction of the acute phase expression of CD70 and CD27 in the leukemic cells increased 38- and 25-fold, respectively. Coexpression of membrane CD70 and CD27 on the leukemic (CD5+CD19+) cells was maximal 2-3 days following initiation of the attack. Soluble CD27 in the patient's serum was elevated during remission and further increased in the attack. Functional tests showed that neither anti-CD70 nor anti-CD27 Abs affect the rate of apoptosis. However, the anti-CD70 Ab specifically enhanced proliferation of the remission phase leukemic cells, whereas proliferation of the acute-phase counterparts that express higher level of membrane CD70 was unaffected. Hence, in this lymphoma/leukemia, membrane CD70 is presented on the leukemic cells in a responsive state during the remission and a nonresponsive state during the attack. Presumably, CD70 in its responsive state provides a costimulatory receptor for initiating the next acute phase while its nonresponsive state enables the remission.
Kaufmann
Yael
Y
Institute of Hematology, Safra Children's Hospital, Tel-Hashomer, Israel. yaelka@sheba.health.gov.il
Amariglio
Ninette
N
Rosenthal
Esther
E
Hirsch
Yasmine Jacob
YJ
Many
Amira
A
Rechavi
Gideon
G
D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis; D001483:Base Sequence; D053282:CD27 Ligand; D002462:Cell Membrane / Q000276:immunology; D049109:Cell Proliferation; D004273:DNA, Neoplasm / Q000235:genetics; D020869:Gene Expression Profiling; D006801:Humans; D007938:Leukemia / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D008024:Ligands; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D012008:Recurrence; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000097:blood / Q000235:genetics; D048069:Tumor Necrosis Factors / Q000235:genetics / Q000378:metabolism*
D015703:Antigens, CD; D053282:CD27 Ligand; C505771:CD70 protein, human; D004273:DNA, Neoplasm; D008024:Ligands; D008565:Membrane Proteins; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D048069:Tumor Necrosis Factors