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Proliferation Response of Leukemic Cells to CD70 Ligation Oscillates with Recurrent Remission and Relapse in a Low-Grade Lymphoma¹

Yael Kaufmann^2,*,, Ninette Amariglio^*,, Esther Rosenthal^*, Yasmine Jacob Hirsch, Amira Many^* and Gideon Rechavi^3,*,,

^* Institute of Hematology and Pediatric Hematology-Oncology, Safra Children’s Hospital, Chaim Sheba Medical Center, Tel-Hashomer, Israel; and Sackler School of Medicine Tel-Aviv University, Tel-Aviv, Israel

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.