Abstract:
Updating the classification of hematologic neoplasia with germline predisposition, pediatric myelodysplastic syndrome (MDS), and juvenile myelomonocytic leukemia (JMML) is critical for diagnosis, therapy, research, and clinical trials. Advances in next-generation sequencing technology have led to the identification of an expanding group of genes that predispose to the development of hematolymphoid neoplasia when mutated in germline configuration and inherited. This review encompasses recent advances in the classification of myeloid and lymphoblastic neoplasia with germline predisposition summarizing important genetic and phenotypic information, relevant laboratory testing, and pathologic bone marrow features. Genes are organized into three major categories including (1) those that are not associated with constitutional disorder and include CEBPA, DDX41, and TP53; (2) those associated with thrombocytopenia or platelet dysfunction including RUNX1, ANKRD26, and ETV6; and (3) those associated with constitutional disorders affecting multiple organ systems including GATA2, SAMD9, and SAMD9L, inherited genetic mutations associated with classic bone marrow failure syndromes and JMML, and Down syndrome. A provisional category of germline predisposition genes is created to recognize genes with growing evidence that may be formally included in future revised classifications as substantial supporting data emerges. We also detail advances in the classification of pediatric myelodysplastic syndrome (MDS), expanding the definition of refractory cytopenia of childhood (RCC) to include early manifestation of MDS in patients with germline predisposition. Finally, updates in the classification of juvenile myelomonocytic leukemia are presented which genetically define JMML as a myeloproliferative/myelodysplastic disease harboring canonical RAS pathway mutations. Diseases with features overlapping with JMML that do not carry RAS pathway mutations are classified as JMML-like. The review is based on the International Consensus Classification (ICC) of Myeloid and Lymphoid Neoplasms as reported by Arber et al. (Blood 140(11):1200-1228, 2022).
摘要:
更新具有种系易感性的血液肿瘤的分类,小儿骨髓增生异常综合征(MDS),幼年型粒单核细胞白血病(JMML)对诊断至关重要,治疗,研究,和临床试验。下一代测序技术的进步已导致鉴定了一组扩展的基因,这些基因在种系构型中突变并遗传时容易发展为血淋巴样瘤变。这篇综述涵盖了具有种系易感性的髓样和淋巴母细胞瘤的分类的最新进展,总结了重要的遗传和表型信息。相关实验室测试,和病理性骨髓特征。基因分为三个主要类别,包括(1)那些与宪法障碍无关的基因,包括CEBPA,DDX41和TP53;(2)与血小板减少症或血小板功能障碍相关的患者,包括RUNX1,ANKRD26和ETV6;(3)与影响多器官系统的结构性疾病相关的患者,包括GATA2,SAMD9和SAMD9L,与经典骨髓衰竭综合征和JMML相关的遗传基因突变,和唐氏综合症。创建了种系易感性基因的临时类别,以识别具有越来越多证据的基因,随着大量支持数据的出现,这些证据可能正式包含在未来修订的分类中。我们还详细介绍了小儿骨髓增生异常综合征(MDS)的分类进展,扩大儿童难治性血细胞减少症(RCC)的定义,以包括具有种系易感性的患者中MDS的早期表现。最后,本文对幼年型粒单核细胞白血病的分类进行了更新,将JMML基因定义为具有经典RAS通路突变的骨髓增生性/骨髓增生异常疾病.具有与不携带RAS途径突变的JMML重叠的特征的疾病被分类为JMML样。该综述基于Arber等人报道的髓样和淋巴样肿瘤的国际共识分类(ICC)。(血脉140(11):1200-1228,2022)。