Wolach Ofir, Stone Richard M
aLeukemia Service, Davidoff Cancer Center, Rabin Medical Center, Petah-Tikva, Israel bDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Curr Opin Hematol. 2017 Mar;24(2):139-145. doi: 10.1097/MOH.0000000000000322.
Mixed-phenotype acute leukemia (MPAL) is a rare disease that poses many diagnostic and therapeutic challenges. Patients with MPAL are considered to have poor outcomes. The difficulties in classifying this leukemia, the lack of prospectively collected data concerning therapeutic outcomes, and rare incidence result in much uncertainty as to the best approach for patients with MPAL.
Recent studies demonstrated that most MPALs are associated with cytogenetic abnormalities; genetic sequencing studies disclose a high frequency of somatic mutations in genes encoding epigenetic regulators, tumor suppressors, and transcription factors. The limited available data suggest that higher remission rates are achieved with acute lymphoblastic leukemia-like induction regimens compared with acute myeloid leukemia-type approaches. Allogeneic transplantation in first remission may be associated with improved survival compared with consolidation chemotherapy.
Advances in understanding the genetic landscape of MPAL may allow a more biologically driven classification of this heterogeneous group of leukemias in the future that will lead to optimized therapies for individual patients. Most data that inform therapy are based on retrospective, uncontrolled studies; prospective trials that incorporate targeted approaches based on genetics and immunophenotype are needed.
混合表型急性白血病（MPAL）是一种罕见疾病，带来了诸多诊断和治疗挑战。MPAL患者的预后被认为较差。这种白血病分类困难、缺乏关于治疗结果的前瞻性收集数据以及发病率低，导致对于MPAL患者的最佳治疗方法存在诸多不确定性。
近期研究表明，大多数MPAL与细胞遗传学异常相关；基因测序研究揭示，编码表观遗传调节因子、肿瘤抑制因子和转录因子的基因中存在高频体细胞突变。有限的现有数据表明，与急性髓系白血病类型的治疗方案相比，急性淋巴细胞白血病样诱导方案可实现更高的缓解率。与巩固化疗相比，首次缓解时进行异基因移植可能与生存率提高相关。
对MPAL基因格局认识的进展可能使未来对这一异质性白血病群体进行更具生物学驱动性的分类，从而为个体患者带来优化治疗。为治疗提供依据的大多数数据基于回顾性、非对照研究；需要开展纳入基于遗传学和免疫表型的靶向治疗方法的前瞻性试验。
