Winters Amanda C, Bernt Kathrin M
Division of Pediatric Hematology/Oncology/BMT, University of Colorado School of Medicine and Children's Hospital Colorado , Aurora, CO , USA.
Front Pediatr. 2017 Feb 9;5:4. doi: 10.3389/fped.2017.00004. eCollection 2017.
The mixed-lineage leukemia 1 (MLL1) gene (now renamed or ) on chromosome 11q23 is disrupted in a unique group of acute leukemias. More than 80 different partner genes in these fusions have been described, although the majority of leukemias result from fusions with one of about six common partner genes. Approximately 10% of all leukemias harbor translocations. Of these, two patient populations comprise the majority of cases: patients younger than 1 year of age at diagnosis (primarily acute lymphoblastic leukemias) and young- to-middle-aged adults (primarily acute myeloid leukemias). A much rarer subgroup of patients with rearrangements develop leukemia that is attributable to prior treatment with certain chemotherapeutic agents-so-called therapy-related leukemias. In general, outcomes for all of these patients remain poor when compared to patients with non- rearranged leukemias. In this review, we will discuss the normal biological roles of MLL1 and its fusion partners, how these roles are hypothesized to be dysregulated in the context of rearrangements, and the clinical manifestations of this group of leukemias. We will go on to discuss the progress in clinical management and promising new avenues of research, which may lead to more effective targeted therapies for affected patients.
位于11号染色体q23区域的混合谱系白血病1（MLL1）基因（现重新命名为 或 ）在一组独特的急性白血病中发生了改变。在这些融合中已描述了80多种不同的伙伴基因，尽管大多数白血病是由与大约六种常见伙伴基因之一的融合所致。所有白血病中约10%存在 易位。其中，两个患者群体占病例的大多数：诊断时年龄小于1岁的患者（主要是急性淋巴细胞白血病）和中青年成年人（主要是急性髓细胞白血病）。一小部分更为罕见的 重排患者会发生白血病，这归因于先前使用某些化疗药物——即所谓的治疗相关白血病。总体而言，与无 重排白血病的患者相比，所有这些患者的预后仍然很差。在本综述中，我们将讨论MLL1及其融合伙伴的正常生物学作用、这些作用在 重排情况下被假设为失调的方式，以及这组白血病的临床表现。我们将接着讨论临床管理方面的进展和有前景的新研究途径，这可能会为受影响的患者带来更有效的靶向治疗。
