Abstract：
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.
摘要：
骨髓增殖性肿瘤（MPN）是一组克隆性造血干细胞疾病，一种或多种造血细胞类型的增殖不受控制。包括骨髓,红细胞和巨核细胞谱系，和最小的成熟缺陷。大多数MPN与明确定义的分子异常相关,所述分子异常涉及编码蛋白酪氨酸激酶的基因,所述蛋白酪氨酸激酶导致下游信号转导途径的组成型激活并赋予细胞增殖和存活优势。全基因组测序分析发现了大多数MPN亚型以及其他骨髓性肿瘤共有的继发性协同突变，并在疾病进展中发挥重要作用。如果没有适当的管理，大多数MPN的自然史包括初始慢性期和终末期。涉及蛋白酪氨酸激酶的分子畸变已用于诊断，分类，检测最小/可测量的残留疾病，和靶向治疗。我们回顾了MPN分子遗传畸变的最新进展，重点是与涉及酪氨酸激酶途径的基因重排或突变相关的MPN。
