Advances of target therapy on NOTCH1 signaling pathway in T-cell acute lymphoblastic leukemia
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(2020) 9:31 Zheng et al. Exp Hematol Oncol https://doi.org/10.1186/s40164-020-00187-x
Open Access
REVIEW
Advances of target therapy on NOTCH1 signaling pathway in T‑cell acute lymphoblastic leukemia Ruyue Zheng†, Menglin Li†, Shujuan Wang* and Yanfang Liu*
Abstract T-cell acute lymphoblastic leukemia (T-ALL) is one of the hematological malignancies. With the applications of chemotherapy regimens and allogeneic hematopoietic stem cell transplantation, the cure rate of T-ALL has been significantly improved. However, patients with relapsed and refractory T-ALL still lack effective treatment options. Gene mutations play an important role in T-ALL. The NOTCH1 gene mutation is the important one among these genetic mutations. Since the mutation of NOTCH1 gene is considered as a driving oncogene in T-ALL, targeting the NOTCH1 signaling patheway may be an effective option to overcome relapsed and refractory T-ALL. This review mainly summarizes the recent research advances of targeting on NOTCH1 signaling pathway in T-ALL. Keywords: T-cell acute lymphoblastic leukemia, NOTCH1, γ-Secretase inhibitors, SERCA inhibitors, Monoclonal antibody Background T-cell acute lymphoblastic leukemia (T-ALL) is a hematological malignancy originating from T-lymphocytes in bone marrow. In recent years, with the advances of chemotherapy and the application of allogeneic hematopoietic stem cell transplantation in the management of T-ALL, the outcomes of this disease have been significantly improved. At the same time, the use of chimeric antigen receptor modified T cell (CAR-T) therapy also provides new and effective immunotherapy for T-ALL [1]. However, some T-ALL patients are refractory to induction therapy, and others responding to induction therapy may relapse and become refractory to salvage therapy. There are no effective treatment options for those patients with poor prognosis. Thus the underlying molecular mechanisms and therapy for refractory and relapsed T-ALL are the main focuses of current researches. With the advance *Correspondence: [email protected]; [email protected] † Ruyue Zheng and Menglin Li contributed equally to this work Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
of state-of-art molecular technology such as next generation DNA sequencing, studies have found that germline or somatic mutations of some genes may play important roles in the occurrence, development, and drug-resistance of T-ALL [2]. The mutation in NOTCH1 gene is one of the important genetic mutations in T-ALL [3, 4]. Studies have shown that NOTCH1 mutations play a role in carcinogenesis or tumor suppression under different cell backgrounds [5, 6]. In T-ALL, NOTCH1 is a driving oncogene, and the dominant active mutations induce the development of pre-T cells to leukemia [7–9]. Therefore, further understandings of the NOTCH1 mutation in T-ALL will shed light on developing targeting therapy for T-ALL patients. Targeting the NOTCH1 signaling pathway may be an optimal management for the trea
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