Human myeloid inhibitory C-lectin: a highly specific and stable acute myeloid leukemia marker.

Abstract

The prognosis of acute myeloid leukemia (AML) is poor because of relapses occurring on conventional chemotherapy. The distinction between leukemic and normal stem cells relies on the expression of antigen combinations defining leukemia-associated immunophenotypes (LAIPs), which are absent or extremely infrequent in normal bone marrow. However, LAIPs are very different from patient to patient and are not necessarily stable over the course of the disease. Accordingly, we addressed the applicability of human myeloid inhibitory C-lectin (hMICL) by flow cytometry as a specific leukemic myeloid stem cell marker for the diagnosis of AML in CD34+ and CD34- cases and evaluated the stability of hMICL during the course of the disease. hMICL expression was assessed in 78 bone marrow aspirate specimens obtained from AML patients at diagnosis (n=40), complete remission (CR) (n=28), and relapse (n=10). AML patients at diagnosis were compared to 20 newly diagnosed acute lymphoblastic leukemia (ALL) patients and 20 healthy controls. hMICL was reevaluated in CR and relapse specimens. hMICL was expressed in 100% AML patients at diagnosis (mean±standard deviation [SD], 60.3±19.9%), both CD34+ and CD34- , but not in ALL (mean±SD, 3.3±1.9%) or healthy controls (mean±SD, 3.4±2.6%) (P<.001). hMICL median fluorescence intensity ratio was higher in AML (mean±SD, 15.9±11.7) compared to ALL (mean±SD, 4.5±1.4) and healthy controls (mean±SD, 4.4±1.6) (P<.001). hMICL was expressed in all studied AML morphologic subtypes. Preserved stable expression of hMICL was found in CR and relapse specimens with no antigen loss. hMICL is a robust pan-AML-associated antigen with excellent diagnostic impact, extreme specificity to AML blasts, and stability throughout the course of the disease. hMICL could be incorporated into the routine flow cytometry setting within the initial diagnostic work-up and follow-up of AML.