Department of Pediatrics, Division of Hematology-Oncology, Montreal Children's Hospital, McGill University Health Centre, Montreal, Quebec, Canada.
Department of Child Health and Human Development, Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
Clin Genet. 2024 Aug;106(2):193-198. doi: 10.1111/cge.14537. Epub 2024 Apr 24.
Acute promyelocytic leukemia (APL) represents 5%-10% of childhood acute myeloid leukemia (AML) and is the most curable subtype of AML. Fanconi anemia (FA) is one of the most common inherited bone marrow failure syndromes caused by biallelic pathogenic variants (PV) in specific DNA-repair genes. Biallelic PVs in FANCD1/BRCA2 (FA-D1) account for 3% of FA and are associated with early-onset leukemia and a high risk of solid tumors. We report a 4 year-old boy from non-consanguineous parents diagnosed with standard risk APL. This child had café-au-lait spots and an extra thumb remnant. Genomic sequencing revealed two PV in FANCD1/BRCA2 confirming a diagnosis of FA-D1. Chromosomal breakage studies were compatible with FA. Each parent carried one variant and had no personal history of cancer. Morphological then molecular remissions were achieved with all-trans retinoic acid and Arsenic trioxide. This patient underwent haploidentical stem cell transplant. In addition to our patient, a literature search revealed four additional patients with APL/FA, with a total of three patients with FA-D1. This raises the possibility of an association between such rare disorders. Practical management of APL in the setting of FA-D1 is discussed with an overview of current evidence and knowledge gaps.
急性早幼粒细胞白血病（APL）占儿童急性髓细胞白血病（AML）的 5%-10%，是 AML 中最可治愈的亚型。范可尼贫血（FA）是最常见的遗传性骨髓衰竭综合征之一，由特定 DNA 修复基因中的双等位致病性变异（PV）引起。FANCD1/BRCA2（FA-D1）中的双等位 PV 占 FA 的 3%，与早发性白血病和实体瘤的高风险相关。我们报告了一名来自非近亲父母的 4 岁男孩，被诊断为标准风险 APL。该患儿有咖啡牛奶斑和多余的拇指残端。基因组测序显示 FANCD1/BRCA2 中有两个 PV，证实了 FA-D1 的诊断。染色体断裂研究与 FA 相符。每位父母携带一个变异体，且无癌症个人史。全反式维甲酸和三氧化二砷使形态和分子达到缓解。该患者接受了半相合干细胞移植。除了我们的患者，文献检索还发现了另外 4 例 APL/FA 患者，其中 3 例为 FA-D1。这增加了这些罕见疾病之间存在关联的可能性。讨论了 FA-D1 患者中 APL 的实际管理，并概述了当前的证据和知识空白。
