CCL17/TARC is elevated in T-LBL but not T-ALL, with NOTCH1 fusions as a potential distinguishing factor.

Abstract

T-cell acute leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL) are regarded as a spectrum of the same disease. 80% of patients survive, but only 15-25% of relapsed patients can be rescued. Risk stratification is based on MRD (in T-ALL) and/or high risk genetics. However, additional biomarkers are needed to early identify high-risk patients who could benefit from more intensive or alternative treatment strategies. T-LBL patients with NOTCH1 gene fusions have recently been identified as a high-risk group with CCL17 as a possible biomarker. This study investigates CCL17 levels in patients with T-LBL as well as T-ALL. We included all children diagnosed with T-ALL between 2018-2024 in the Netherlands. Blood samples of 38 T-ALL patients were available for retrospective CCL17 measurements. Additionally, we included 36 T-LBL patients diagnosed between 2018-2024 for whom CCL17 values at time of diagnosis were available. CCL17 levels were measured by enzyme-linked immunosorbent assay. CCL17 was not elevated in T-ALL patients (range 38-593 pg/mL). 9 T-LBL patients had elevated levels of CCL17, which was strongly correlated with the presence of NOTCH1 fusions (p<0,001). Additionally, the incidence of relapse was significantly higher for T-LBL patients with elevated CCL17, compared to patients with normal CCL17 (p=0,002). Elevated CCL17 was not correlated with mediastinal enlargement in T-ALL (r=0,28) or T-LBL (r=0,14). These results suggest that CCL17 is a high risk biomarker for T-LBL but not T-ALL, with NOTCH1 fusions as a possible discriminator. Further research is necessary to translate these findings into clinical applications.