Expression of JL1 Antigen in Acute Leukemia and Myelodysplastic Syndrome

Background: The JL1 antigen is a novel epitope of CD43, a cell surface glycoprotein of mucin family. JL1 is a differentiation antigen expressed on stage II double positive (CD4+CD8+) human cortical thymocytes. The antigen is not expressed on mature peripheral blood cells or other normal tissues. The anti-JL1 monoclonal antibody binds to human leukemia MOLT-4 cells with 5,100-9,600 binding sites per cell. Preclinical studies have shown the cytotoxic effects of anti-JL1-based immunotoxin against JL1-positive leukemic cells, sparing most normal tissues other than thymocytes and some bone marrow mononuclear cells. Phase I clinical trial of new anti-leukemic agent with an anti-JL1 antibody (Leukotuximab; DiNonA, Korea) is now underway. In this study, we prospectively investigated the JL1 expression in patients with acute leukemia and myelodysplastic syndrome (MDS).

Patients & methods: Flow cytometric analysis for the JL1 expression on leukemic blasts was performed using a FACSCanto II (Becton-Dickinson, Sunnyvale, CA, USA). The percent expression of JL1 antigen among leukemic blasts was recorded. Positive JL1 expression was defined if 20% or more leukemic blasts expressed the antigen. Association of JL1 expression with clinical, pathologic, and genetic characteristics was analyzed. Influence of JL1 expression on clinical outcomes of patients was also explored.

Results: Between March 2014 and June 2015, a total of 245 adult patients with acute myeloid leukemia (AML, n=170), acute lymphoblastic leukemia (ALL, n=52), and MDS (n=23) were enrolled in this study. Positive JL1 expression was observed in 96 (57.1%) patients with AML, 28 (51.9%) with ALL, and 5 (21.7%) with MDS (P=0.006), while three normal controls showed negative JL1 antigen expression. Interestingly, JL1 expression was positive in all 14 patients with AML M3 with a median expression of 94.3% (range, 60.3-97.8%). In contrast, only 13 (39.4%) of 33 patients with AML with myelodysplasia-related changes (MRC) had positive JL1 expression. In AML patients, positive JL1 expression was significantly associated with CD34- (P=0.003), HLA-DR- (P=0.019), PML-RARA+ (P=0.001), FLT3-ITD+ (P=0.026), mutated NPM1 (P=0.003), and complex karyotype (3 or more clonal chromosomal abnormalities) (P=0.020). Cytarabine plus anthracycline based chemotherapy was given to 117 patients with AML, and the complete remission (CR) rate was significantly different between 63 JL1 expression positive patients and 54 negative patients (84.1% vs. 59.3%, P=0.003). Positivity of JL1 expression was not significantly associated with overall survival in all patients with AML (median survival, JL1 positive vs. negative, 20.6 vs. 18.2 months, P=0.489). In ALL patients, positive JL1 expression was significantly associated with CD13- (P=0.032) and the CR rate was not significantly different by JL1 expression. JL1 expression was measured twice or more in 85 patients during their clinical courses and positivity of JL1 expression was not changed in 61 (71.8%) (P=0.307). Five MDS patients progressed to AML and JL1 expression was changed in only one patient (JL1 positive to JL1 negative).

Conclusion: JL1 was expressed in around 50% of patients with AML or ALL while less frequent expression of JL1 was observed in MDS and AML with MRC. JL1 expression was significantly associated with some immunophenotypic and genetic features, especially PML-RARA+. JL1 expression was significantly associated with the CR rate of AML patients. Expression of JL1 seems to be stable during clinical courses. Our data suggest that immunotherapeutic approach targeting JL1 antigen may be feasible in significant proportion of patients with acute leukemia and MDS.