Department of Leukemia, UT MD Anderson Cancer Center, 1515 Holcombe Blvd (Unit 428), Houston, TX, 77030, USA.
Department of Internal Medicine, University of New Mexico, Albuquerque, NM, USA.
Ann Hematol. 2018 Nov;97(11):2071-2080. doi: 10.1007/s00277-018-3402-x. Epub 2018 Jun 27.
Myeloproliferative neoplasms (MPNs) are clonal disorders characterized by proliferation of one or more elements of the myeloid lineage. Key genetic aberrations include the BCR-ABL1 gene rearrangement in Philadelphia chromosome-positive chronic myelogenous leukemia (CML) and JAK2/MPL/CALR aberrations in Philadelphia chromosome-negative MPNs. While thought to be mutually exclusive, occasional isolated reports of coexistence of BCR-ABL1 and JAK2, and JAK2 with MPL or CALR aberrations have been described. Given the paucity of data, clinical characteristics and outcome of patients harboring concurrent Philadelphia-positive and Philadelphia-negative mutations or dual Philadelphia-negative driver mutations have not been systematically evaluated, and their clinical relevance is largely unknown. It is difficult to determine the true relevance of co-existing driver mutations on outcomes given the rarity of its occurrence. In this case series, we describe those patients who had dual driver mutations detected at any point during the course of their disease and characterized their clinical and laboratory features, bone marrow pathology, and overall disease course.
骨髓增殖性肿瘤（MPN）是一种以髓系细胞异常增生为特征的克隆性疾病。关键的遗传异常包括费城染色体阳性慢性髓系白血病（CML）中的 BCR-ABL1 基因重排和费城染色体阴性 MPN 中的 JAK2/MPL/CALR 异常。虽然认为它们是相互排斥的，但偶尔也有孤立的报告描述了 BCR-ABL1 和 JAK2 以及 JAK2 与 MPL 或 CALR 异常的共存。鉴于数据有限，同时携带费城阳性和费城阴性突变或双重费城阴性驱动突变的患者的临床特征和结局尚未得到系统评估，其临床相关性在很大程度上尚不清楚。由于其发生的罕见性，很难确定共存驱动突变对结局的真正相关性。在本病例系列中，我们描述了在疾病过程中的任何时间点检测到双重驱动突变的患者，并描述了他们的临床和实验室特征、骨髓病理学和整体疾病过程。
