骨髓增生性肿瘤（MPN）是一组克隆的造血干细胞障碍，其中一个或多个造血细胞系（包括髓系、红系和巨核系）未受到成熟的最小限制而不受控制地增殖。大多数MPN与编码蛋白酪氨酸激酶基因的明确定义的分子异常相关，这些异常导致下游信号转导通路的常规激活，并赋予细胞增殖和生存优势。全基因组测序分析发现了次要协同突变，这些突变由大多数MPN亚型以及其他髓系肿瘤共享，并在疾病进展中发挥重要作用。如果没有适当的治疗，大多数MPN的自然历史包括一个初始的慢进展期和一个末期的爆发期。涉及蛋白质酪氨酸激酶的分子异常已被用于诊断、分类、检测最小/可测残留病以及靶向治疗。我们重点评述了与酪氨酸激酶通路相关的基因重排或突变的MPN分子遗传异常的最新进展。版权所有 © 2023 Elsevier Inc.。

Myeloproliferative neoplasms (MPN) are a group of clonal hematopoietic stem cell disorders with uncontrolled proliferation of one or more hematopoietic cell types, including myeloid, erythroid and megakaryocytic lineages, and minimal defect in maturation. Most MPN are associated with well-defined molecular abnormalities involving genes that encode protein tyrosine kinases that lead to constitutive activation of the downstream signal transduction pathways and confer cells proliferative and survival advantage. Genome-wide sequencing analyses have discovered secondary cooperating mutations that are shared by most of the MPN subtypes as well as other myeloid neoplasms and play a major role in disease progression. Without appropriate management, the natural history of most MPN consists of an initial chronic phase and a terminal blast phase. Molecular aberrations involving protein tyrosine kinases have been used for the diagnosis, classification, detection of minimal/measurable residual disease, and target therapy. We review recent advances in molecular genetic aberrations in MPN with a focus on MPN associated with gene rearrangements or mutations involving tyrosine kinase pathways.Copyright © 2023 Elsevier Inc. All rights reserved.