Circulating Ki-67 protein in plasma as a biomarker and prognostic indicator of acute lymphoblastic leukemia

Tissue-based determination of Ki-67, a marker of cellular proliferation, has shown prognostic value in solid tumors and hematological malignancies. We developed and validated an electrochemiluminescence-based method for sensitive measurement of circulating Ki-67 in plasma (cKi-67). This assay demonstrated significantly higher levels of cKi-67 in patients with newly diagnosed acute lymphoblastic leukemia (ALL) (n = 27; median, 762; range, 0–4574 U/100 μL) than in healthy control subjects (n = 114; median, 399; range, 36–2830 U/100 μL). Moreover, elevated plasma cKi-67 was associated with significantly shorter survival in ALL patients (P = 0.05). These findings suggest that Ki-67 can be detected in circulation and has potential for use as a biomarker for predicting clinical behavior in ALL.