B-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 that ECM1 transcript 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 of ECM1transcript level at diagnosis was 0.89 (P <0.001). Patients with BCR::ABL1and IKZF1 deletion show highest expression level (210.78%) compared with KMT2A rearrangement (39.48%) and TCF3::PBX1 rearrangement ones (30.02%) (all P <0.05). Also, the expression level of ECM1 was highly correlated with the clinical course, as 20 consecutive follow-up cases indicated. The 5-year OS of patients (non-KMT2A and non-TCF3::PBX1rearrangement) with high ECM1 transcript level was significantly worse than the lower ones (18.7% vs. 72.9%, P <0.001) and high ECM1transcript level was an independent risk factor for OS (HR=5.77 [1.75-19.06], P=0.004). After considering transplantation, high ECM1 transcript level was not an independent risk factor, although OS was still poor (low vs.high, 71.1% vs. 56.8%, P =0.038). Our findings suggested that ECM1may be a potential molecular marker for diagnosis, minimal residual disease (MRD) monitoring, and prognosis prediction of B-cell ALL.
Trial Registration
Trial 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.