Increased ADAM28 Levels In Plasma and Bone Marrow Cells of Patients With Adult Acute Leukemia

ADAM28, a member of the ADAM (A Disintegrin And Metalloproteinase) family, cleaves various substrates including von Willebrand factor. Two isoforms of ADAM28: the membrane associated (ADAM28m) and the secreted (ADAM28s) were identified. Both were overexpressed in solid tumors including breast carcinoma, non-small cell lung cancer, and bladder transitional cell carcinoma. Overexpression of ADAM28 has been shown to promote cell growth, invasion, and metastasis of solid tumors in humans. However, little is known about expression and potential role of ADAM28 in hematological malignancies. In this study, we determined ADAM28 protein and/or mRNA expression in plasma and/or bone marrow cells of patients with various acute and chronic leukemia. An informed consent was obtained from all participants. Plasma and bone marrow aspirates were obtained from a total of 65 patients including 24 patients with acute lymphoblastic leukemia (ALL), 23 patients acute myelocytic leukemia (AML), and 18 patients with other leukemia. Twenty one healthy volunteers were also included in the study (Table 1). By flow cytometry, we showed that mean fluorescent index ratios that are specific for ADAM28m were significantly <>

<>increased in the bone marrow malignant cells in patients with ALL (2.9±0.13) and AML (2.1±0.17) compared with those in the control (0.4±0.06). The p values were <0.01 and <0.05, respectively. In addition, plasma levels of ADAM28s antigen assessed by a specific sandwich ELISA were significantly higher in patients with ALL (386.1±44.6 pg/ml) (p<0.01) and AML (291.3±24.0 pg/ml) (p<0.05) than those in the control (120.7±12.1 pg/ml). Furthermore, the mRNA levels encoding ADAM28m (1.7±0.0) and ADAM28s (2.9±0.1) in the bone marrow cells were significantly higher than those in the control (p< 0.05) (Table 1). Interestingly, cellular ADAM28 overexpression was inversely associated with cellular apoptosis in ALL patients. In four ALL patients with an early relapse, ADAM28 levels (both protein and mRNA) in bone marrow cells were significantly higher than those in patients with complete remission. In conclusion, our data indicate for the first time that a measurement of plasma and bone marrow ADAM28 levels may help identify patients with high risk of early relapse. Whether a treatment that targets ADAM28 has an effect in adult acute leukemia remains to be determined.

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