Machado-Neto João Agostinho, Rodrigues Alves Ana Paula Nunes, Fernandes Jaqueline Cristina, Coelho-Silva Juan Luiz, Scopim-Ribeiro Renata, Fenerich Bruna Alves, da Silva Fernanda Borges, Scheucher Priscila Santos, Simões Belinda Pinto, Rego Eduardo Magalhães, Traina Fabiola
Department of Internal Medicine, University of São Paulo at Ribeirão Preto Medical School, Ribeirão Preto, São Paulo, Brazil.
Heliyon. 2017 Sep 28;3(9):e00405. doi: 10.1016/j.heliyon.2017.e00405. eCollection 2017 Sep.
Acute lymphoblastic leukemia (ALL) is a hematological malignancy characterized by abnormal proliferation and accumulation of lymphoblasts in the hematopoietic system. Stathmin 1 is a proliferation marker for normal lymphocytes, which has been described as highly expressed in ALL patients and functionally important for leukemia phenotype. In the present study, we expand our previous observations and aim to investigate expression and its impact on laboratory features and clinical outcomes in an independent cohort of ALL patients, and to verify the effects of paclitaxel treatment on Stathmin 1 phosphorylation and cell viability in ALL cell lines. In ALL patients, expression was significantly increased, associated with lower age onset and positively correlated with white blood cell counts, but did not impact on clinical outcomes. Functional assays revealed that paclitaxel induces Stathmin 1 phosphorylation at serine 16 (an inhibitory site), microtubule stability and apoptosis in Jurkat and Namalwa cell lines. Paclitaxel treatment did not modulate cell viability of normal peripheral blood leukocytes. In conclusion, our data confirm increased levels of Stathmin 1 in ALL patients and that therapeutic doses of paclitaxel inhibits Stathmin 1 function and promote microtubule stability and apoptosis in ALL cells.
急性淋巴细胞白血病（ALL）是一种血液系统恶性肿瘤，其特征是造血系统中淋巴母细胞异常增殖和积聚。Stathmin 1是正常淋巴细胞的增殖标志物，在ALL患者中高表达，对白血病表型具有重要功能。在本研究中，我们扩展了之前的观察结果，旨在调查ALL患者独立队列中Stathmin 1的表达及其对实验室特征和临床结局的影响，并验证紫杉醇治疗对ALL细胞系中Stathmin 1磷酸化和细胞活力的影响。在ALL患者中，Stathmin 1表达显著增加，与发病年龄较低相关，与白细胞计数呈正相关，但不影响临床结局。功能分析表明，紫杉醇可诱导Jurkat和Namalwa细胞系中Stathmin 1丝氨酸16位点（一个抑制位点）的磷酸化、微管稳定性和细胞凋亡。紫杉醇治疗未调节正常外周血白细胞的细胞活力。总之，我们的数据证实ALL患者中Stathmin 1水平升高，且治疗剂量的紫杉醇可抑制ALL细胞中Stathmin 1功能，促进微管稳定性和细胞凋亡。
