Barreto Igor Valentim, Pessoa Flávia Melo Cunha de Pinho, Machado Caio Bezerra, Pantoja Laudreísa da Costa, Ribeiro Rodrigo Monteiro, Lopes Germison Silva, Amaral de Moraes Maria Elisabete, de Moraes Filho Manoel Odorico, de Souza Lucas Eduardo Botelho, Burbano Rommel Mário Rodriguez, Khayat André Salim, Moreira-Nunes Caroline Aquino
Department of Medicine, Pharmacogenetics Laboratory, Drug Research and Development Center (NPDM), Federal University of Ceará, Fortaleza, Brazil.
Department of Pediatrics, Octávio Lobo Children's Hospital, Belém, Brazil.
Front Oncol. 2022 Jun 24;12:931050. doi: 10.3389/fonc.2022.931050. eCollection 2022.
Hematopoietic stem cells (HSCs) are known for their ability to proliferate and self-renew, thus being responsible for sustaining the hematopoietic system and residing in the bone marrow (BM). Leukemic stem cells (LSCs) are recognized by their stemness features such as drug resistance, self-renewal, and undifferentiated state. LSCs are also present in BM, being found in only 0.1%, approximately. This makes their identification and even their differentiation difficult since, despite the mutations, they are cells that still have many similarities with HSCs. Although the common characteristics, LSCs are heterogeneous cells and have different phenotypic characteristics, genetic mutations, and metabolic alterations. This whole set of alterations enables the cell to initiate the process of carcinogenesis, in addition to conferring drug resistance and providing relapses. The study of LSCs has been evolving and its application can help patients, where through its count as a biomarker, it can indicate a prognostic factor and reveal treatment results. The selection of a target to LSC therapy is fundamental. Ideally, the target chosen should be highly expressed by LSCs, highly selective, absence of expression on other cells, in particular HSC, and preferentially expressed by high numbers of patients. In view of the large number of similarities between LSCs and HSCs, it is not surprising that current treatment approaches are limited. In this mini review we seek to describe the immunophenotypic characteristics and mechanisms of resistance presented by LSCs, also approaching possible alternatives for the treatment of patients.
造血干细胞(HSCs)以其增殖和自我更新能力而闻名,因此负责维持造血系统并存在于骨髓(BM)中。白血病干细胞(LSCs)以其干性特征如耐药性、自我更新和未分化状态而被识别。LSCs也存在于骨髓中,大约仅占0.1%。这使得它们的识别甚至分化都很困难,因为尽管存在突变,但它们仍然是与HSCs有许多相似之处的细胞。尽管有共同特征,但LSCs是异质性细胞,具有不同的表型特征、基因突变和代谢改变。这一系列改变不仅使细胞能够启动致癌过程,还赋予了耐药性并导致复发。对LSCs的研究一直在发展,其应用可以帮助患者,通过将其计数作为生物标志物,可以指示预后因素并揭示治疗结果。选择LSC治疗的靶点至关重要。理想情况下,选择的靶点应该在LSCs中高表达,具有高度选择性,在其他细胞尤其是HSC上不表达,并且在大量患者中优先表达。鉴于LSCs和HSCs之间存在大量相似之处,当前的治疗方法有限也就不足为奇了。在这篇小型综述中,我们试图描述LSCs呈现的免疫表型特征和耐药机制,同时探讨治疗患者的可能替代方案。