Alarcón-Payer Carolina, Sánchez Suárez María Del Mar, Martín Roldán Alicia, Puerta Puerta José Manuel, Jiménez Morales Alberto
Servicio de Farmacia, Hospital Universitario Virgen de las Nieves, 18014 Granada, Spain.
Unidad de Gestión Clínica Hematología y Hemoterapia, Hospital Universitario Virgen de las Nieves, 18014 Granada, Spain.
J Pers Med. 2022 Sep 29;12(10):1607. doi: 10.3390/jpm12101607.
Most malignant hematological diseases are generally a consequence of acquired mutations or rearrangements in cell replication processes. Acute myeloid leukemia (AML) is a clinically and molecularly heterogeneous disease that results from acquired genetic and epigenetic alterations in hematopoietic progenitor cells. Despite the advances made in understanding the pathogenesis of this disease, the overall survival of patients remains very low due to the high relapse rate. Pharmacogenetics and massive sequencing studies have allowed the identification of new recurrent mutations with significant prognostic impact in AML; furthermore, it seems likely that whole genome sequencing will soon become a standard diagnostic test, which will allow the molecular diagnosis of patients. Therefore, it is necessary to develop molecular targets that open new therapeutic perspectives and allow individualized treatment of patients with this aggressive disease. Chronic myeloid leukemia (CML) is the first neoplastic disease for which a characteristic genetic alteration was described. It has, by definition, a genetic marker, the BCR::ABL1 rearrangement, as a consequence of the t9;22(q34;q11) translocation. Its study is essential for the diagnosis of this entity and also for monitoring the response to treatment. Drugs known as tyrosine kinase inhibitors (TKIs) that target the BCR::ABL1 protein (oral targeted therapy) are the conventional treatment of CML, representing a change of paradigm in the management of oncohematological patients.
大多数恶性血液病通常是细胞复制过程中获得性突变或重排的结果。急性髓系白血病（AML）是一种临床和分子层面均具有异质性的疾病，由造血祖细胞中获得性基因和表观遗传改变引起。尽管在理解该疾病发病机制方面取得了进展，但由于高复发率，患者的总体生存率仍然很低。药物遗传学和大规模测序研究已使人们能够识别出对AML具有显著预后影响的新的复发性突变；此外，全基因组测序似乎很快将成为一种标准诊断测试，这将有助于对患者进行分子诊断。因此，有必要开发分子靶点，以开拓新的治疗前景，并实现对这种侵袭性疾病患者的个体化治疗。慢性髓系白血病（CML）是第一种被描述有特征性基因改变的肿瘤性疾病。根据定义，它有一个遗传标记，即由于t9;22（q34;q11）易位导致的BCR::ABL1重排。对其进行研究对于诊断该疾病以及监测治疗反应都至关重要。靶向BCR::ABL1蛋白的称为酪氨酸激酶抑制剂（TKIs）的药物（口服靶向治疗）是CML的常规治疗方法，代表了血液肿瘤患者管理模式的转变。
