Molecular mechanism of KIF21B in pediatric acute T lymphoblastic leukemia

Main Article Content

Yu Sun
Yuhao Xu
Chao Lu

Abstract

Our study aims to explore the molecular mechanism of KIF21B (Kinesin family member 21B, KIF21B) in pediatric acute T-lymphocytic leukemia. Jurkat cell lines were selected into over-expression group and knockdown knockdown group. western blotting, cell flow cytometry, CCK-8 and immunofluorescence were used to detect our results. The protein level of KIF21b in over-expression group was significantly higher than knockdown group (P<0.05); The G1 phase of KIF21B cells in over-expression group was obviously shortened, while the G1 phase of KIF21B cells in knockdown group was distinctly prolonged (P<0.05); The proliferation rate of cells in over-expression group was distinctly higher than knockdown group (P<0.05); The TORC1 signaling pathway related proteins in over-expression group were obviously higher than knockdown group (P<0.05); Over-expression of KIF21b can activate the MTORC1 signaling pathway, while knocking down KIF21b significantly inhibits the activity of the MTORC1 signaling pathway; KIF21B makes regulations on activating the MTORC1 pathway by affecting the localization of the MTORC1 complex in cells. Our results indicated that Over-expression of KIF21b affects the localization of mTOR protein cells and activates the MTORC1 signaling pathway to promote the occurrence and development of T-ALL. KIF21B has important potential value in disease diagnosis and treatment.

Article Details

Section
Research Articles

References

[1] Lato MW, Przysucha A, Grosman S, Zawitkowska J, Lejman M. The New Therapeutic Strategies in Pediatric T-Cell Acute Lymphoblastic Leukemia. Int J Mol Sci. 2021;22(9):4502.

[2] Inaba H, Pui C-H. Immunotherapy in pediatric acute lymphoblastic leukemia. Cancer Metastasis Rev. 2019;38(4):595-610.

[3] Ni S, Li J, Qiu S, Xie Y, Gong K, Duan Y. KIF21B Expression in Osteosarcoma and Its Regulatory Effect on Osteosarcoma Cell Proliferation and 595-Apoptosis Through the PI3K/AKT Pathway. Front Oncol. 2021;10:606765.

[4] Yang K, Xu J, Liu Q, Li J, Xi Y. Expression and significance of CD47, PD1 and PDL1 in T-cell acute lymphoblastic lymphoma/leukemia. Pathol Res Pract. 2019;215(2):265-71.

[5] Whitlock JA, Malvar J, Dalla-Pozza L, Goldberg JM, Silverman LB, Ziegler DS. Nelarabine, etoposide, and cyclophosphamide in relapsed pediatric T-acute lymphoblastic leukemia and T-lymphoblastic lymphoma (study T2008-002 NECTAR). Pediatr Blood Cancer. 2022;69(11):e29901.

[6] Rujkijyanont P, Inaba H. Diagnostic and treatment strategies for pediatric acute lymphoblastic leukemia in low- and middle-income countries. Leukemia. 2024;38(8):1649-62.

[7] Teachey DT, Devidas M, Wood BL, Chen Z, Hayashi RJ. Children’s Oncology Group Trial AALL1231: A Phase III Clinical Trial Testing Bortezomib in Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia and Lymphoma. J Clin Oncol. 2022;40(19):2106-18.

[8] Pinazza M, Ghisi M, Minuzzo S, Agnusdei V, Fossati G, Ciminale V, et al. Histone deacetylase 6 controls Notch3 trafficking and degradation in T-cell acute lymphoblastic leukemia cells. Oncogene. 2018;37(28):3839-51.

[9] Laukkanen S, Veloso A, Yan C, Oksa L, Alpert EJ. Therapeutic targeting of LCK tyrosine kinase and mTOR signaling in T-cell acute lymphoblastic leukemia. Blood. 2022;140(17):1891-906.

[10] Khan M, Siddiqi R, Tran TH. Philadelphia chromosome-like acute lymphoblastic leukemia: A review of the genetic basis, clinical features, and therapeutic options. Semin Hematol. 2018;55(4):235-41.

[11] Xue Y, Wang Y, Lu A, Jia Y, Zuo Y. Clinical Analysis of Pediatric T-Cell Acute Lymphoblastic Leukemia Using the MRD-Oriented Strategy System. Clin Lymphoma Myeloma Leuk. 2023;23(7):477-83.

[12] Liu K, Chu J, Dai Y, Jiang A, Yang L, Xie Z, et al. Long-term follow-up of acute lymphoblastic leukemia in young children treated by the SCMC-ALL-2009 protocol. Leuk Lymphoma. 2020;61(12):2850-8.

[13] Bontoux C, Simonin M, Garnier N, Lhermitte L, Touzart A, Andrieu G. Oncogenetic landscape of T-cell lymphoblastic lymphomas compared to T-cell acute lymphoblastic leukemia. Mod Pathol. 2022;35(9):1227-35.

[14] Zwet JCGvd, Cordo' V, Canté-Barrett K, Meijerink JPP. Multi-omic approaches to improve outcome for T-cell acute lymphoblastic leukemia patients. Adv Biol Regul. 2019;74:100647.

[15] Jia M, Hu B, Xu X, Zhang J, Li S, Tang Y. Clinical features and prognostic impact of TCF3-PBX1 in childhood acute lymphoblastic leukemia: A single-center retrospective study of 837 patients from China. Curr Probl Cancer. 2021;45(6):100758.

[16] Senthilkumar R, Chen B, Cai X, Fu R. Anticancer and multidrug-resistance reversing potential of traditional medicinal plants and their bioactive compounds in leukemia cell lines. Chin J Nat Med. 2014;12(12):881-94.

[17] Pikman Y, Alexe G, Roti G, Conway AS, Furman A, Lee ES, et al. Synergistic Drug Combinations with a CDK4/6 Inhibitor in T-cell Acute Lymphoblastic Leukemia. Clin Cancer Res. 2017;23(4):1012-24.

[18] Wilhelmina E van Riel AR, Sarah Bianchi, Eugene A Katrukha, Qingyang Liu, Albert Jr Heck, Casper C Hoogenraad, Michel O Steinmetz, Lukas C Kapitein, Anna Akhmanova. Kinesin-4 KIF21B is a potent microtubule pausing factor. Elife. 2017;6:e24746.

[19] Paolino J, Dimitrov B, Winger BA, Sandoval-Perez A, Rangarajan AV, Ocasio-Martinez N. Integration of Genomic Sequencing Drives Therapeutic Targeting of PDGFRA in T-Cell Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma. Clin Cancer Res. 2023;29(22):4613-26.

[20] Cordo' V, Zwet JCGvd, Canté-Barrett K, Pieters R, Meijerink JPP. T-cell Acute Lymphoblastic Leukemia: A Roadmap to Targeted Therapies. Blood Cancer Discov. 2021;2(1):19-31.