Ajufo Helen O, Waksal Julian A, Mascarenhas John O, Rampal Raajit K
Memorial Sloan Kettering Cancer Center, New York, NY, USA.
The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Ther Adv Hematol. 2023 Jun 22;14:20406207231177282. doi: 10.1177/20406207231177282. eCollection 2023.
Myeloproliferative neoplasms (MPNs) are a group of clonal hematologic malignancies that include polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF). MPNs are characterized by activating mutations in the JAK/STAT pathway and an increased risk of transformation to an aggressive form of acute leukemia, termed MPN-blast phase (MPN-BP). MPN-BP is characterized by the presence of ⩾20% blasts in the blood or bone marrow and is almost always preceded by an accelerated phase (MPN-AP) defined as ⩾10-19% blasts in the blood or bone marrow. These advanced forms of disease are associated with poor prognosis with a median overall survival (mOS) of 3-5 months in MPN-BP and 13 months in MPN-AP. MPN-AP/BP has a unique molecular landscape characterized by increased intratumoral complexity. Standard therapies used in acute myeloid leukemia (AML) have not demonstrated improvement in OS. Allogeneic hematopoietic stem cell transplant (HSCT) remains the only curative therapy but is associated with significant morbidity and mortality and infrequently utilized in clinical practice. Therefore, an urgent unmet need persists for effective therapies in this advanced phase patient population. Here, we review the current management and future directions of therapy in MPN-AP/BP.
骨髓增殖性肿瘤（MPNs）是一组克隆性血液系统恶性肿瘤，包括真性红细胞增多症（PV）、原发性血小板增多症（ET）和骨髓纤维化（MF）。MPNs的特征是JAK/STAT通路中的激活突变以及转化为侵袭性急性白血病（称为MPN急变期，MPN-BP）的风险增加。MPN-BP的特征是血液或骨髓中存在≥20%的原始细胞，并且几乎总是先出现加速期（MPN-AP），加速期定义为血液或骨髓中原始细胞占10%-19%。这些疾病的晚期形式预后较差，MPN-BP的中位总生存期（mOS）为3-5个月，MPN-AP为13个月。MPN-AP/BP具有独特的分子格局，其特征是肿瘤内复杂性增加。急性髓系白血病（AML）中使用的标准疗法尚未显示总生存期有所改善。异基因造血干细胞移植（HSCT）仍然是唯一的治愈性疗法，但与显著的发病率和死亡率相关，在临床实践中很少使用。因此，对于这一晚期患者群体，迫切需要有效的治疗方法。在此，我们综述了MPN-AP/BP的当前管理和未来治疗方向。
