Extracellular matrix protein 1 (ECM1) is a potential biomarker in B-cell acute lymphoblastic leukemia

Abstract

AbstractB-cell acute lymphoblastic leukemia (ALL) is characterized by the highly heterogeneity of pathogenic genetic background, and there are still approximately 30-40% of patients without clear molecular markers. To identify the dysregulated genes in B-cell ALL, we screened 30 newly diagnosed B-cell ALL patients and 10 donors by gene expression profiling chip. We found thatECM1transcript level was abnormally elevated in newly diagnosed B-cell ALL and further verified in another 267 cases compared with donors (median, 124.57%vs.7.14%,P<0.001). ROC analysis showed that the area under the curve ofECM1transcript level at diagnosis was 0.89 (P<0.001). Patients withBCR::ABL1andIKZF1deletion show highest expression level (210.78%) compared withKMT2Arearrangement (39.48%) andTCF3::PBX1rearrangement ones (30.02%) (allP<0.05). Also, the expression level ofECM1was highly correlated with the clinical course, as 20 consecutive follow-up cases indicated. The 5-year OS of patients (non-KMT2Aand non-TCF3::PBX1rearrangement) with highECM1transcript level was significantly worse than the lower ones (18.7%vs.72.9%,P<0.001) and highECM1transcript level was an independent risk factor for OS (HR=5.77 [1.75-19.06],P=0.004). After considering transplantation, highECM1transcript level was not an independent risk factor, although OS was still poor (lowvs.high, 71.1%vs.56.8%,P=0.038). Our findings suggested thatECM1may be a potential molecular marker for diagnosis, minimal residual disease (MRD) monitoring, and prognosis prediction of B-cell ALL.Trial RegistrationTrial Registration Registered in the Beijing Municipal Health Bureau Registration N 2007–1007 and in the Chinese Clinical Trial Registry [ChiCTR-OCH-10000940 and ChiCTR-OPC-14005546]; http://www.chictr.org.cn.