National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of Hematology, Peking University People's Hospital, Peking University Institute of Hematology, Beijing, China.
Haematology Research Center, Division of Experimental Medicine, Department of Medicine, Imperial College London, London, UK.
Br J Haematol. 2020 Jul;190(1):67-78. doi: 10.1111/bjh.16505. Epub 2020 Feb 18.
Dehydropeptidase-1 (DPEP1) is a zinc-dependent metalloproteinase abnormally expressed in many cancers. However, its potential role in adults with B cell acute lymphoblastic leukaemia (ALL) is unknown. We found that in adults with common B cell ALL high DPEP1, transcript levels at diagnosis were independently associated with an increased cumulative incidence of relapse (CIR) and worse relapse-free survival (RFS) compared with subjects with low transcript levels. We show an increased proliferation and prosurvival role of DPEP1 in B cell ALL cells via regulation of phosphCREB and p53, which may be the biological basis of the clinical correlation we report. Our data implicate DPEP1 expression in the biology of common B cell ALL in adults. We report clinical correlates and provide a potential biological basis for these correlations. If confirmed, analysing DPEP1 transcript levels at diagnosis could help predict therapy outcomes. Moreover, regulation of DPEP1 expression could be a therapy target in B cell ALL.
脱肽酶-1（DPEP1）是一种锌依赖性金属蛋白酶，在许多癌症中异常表达。然而，其在成人 B 细胞急性淋巴细胞白血病（ALL）中的潜在作用尚不清楚。我们发现，在常见 B 细胞 ALL 成人患者中，高 DPEP1 转录水平与诊断时与低转录水平患者相比，累积复发率（CIR）增加和无复发生存率（RFS）降低独立相关。我们通过调节磷酸化 CREB 和 p53，证明了 DPEP1 在 B 细胞 ALL 细胞中的增殖和生存促进作用，这可能是我们报告的临床相关性的生物学基础。我们的数据表明 DPEP1 表达与成人常见 B 细胞 ALL 的生物学有关。我们报告了临床相关性，并为这些相关性提供了潜在的生物学基础。如果得到证实，分析诊断时的 DPEP1 转录水平可能有助于预测治疗结果。此外，DPEP1 表达的调节可能是 B 细胞 ALL 的治疗靶点。
