Vyas Paresh, Roberts Irene
Department of Haematology, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital and University of Oxford, Oxford, UK.
Early Hum Dev. 2006 Dec;82(12):767-73. doi: 10.1016/j.earlhumdev.2006.09.016. Epub 2006 Oct 24.
Newborns and children with Down Syndrome are predisposed to a range of blood disorders, which include acute lymphoblastic leukaemia and acute megakaryocytic leukaemia (AMKL). Over the last four years there has been considerable progress in our understanding of DS AMKL. Like other childhood leukaemias DS AMKL is initiated in utero and can present in the neonatal period as a clinically overt preleukaemic condition, transient myeloproliferative disorder (TMD). In addition to trisomy 21, fetal haemopoietic progenitors acquire N-terminal truncating mutations in the key megakaryocyte-erythroid transcription factor GATA1. These are the minimum required events for TMD to develop. In approximately 30% of TMD patients, additional as yet unidentified (epi)genetic mutations are required for progression to AMKL. Thus, DS TMD and AMKL provide a unique model of childhood leukaemia where the preleukaemic and leukaemic phases are ascertainable and separable allowing distinct steps in leukaemogenesis to be studied individually. These findings also have implications for the clinical management of DS TMD and AMKL specifically and also of childhood leukaemia more generally.
唐氏综合征患儿易患一系列血液疾病，其中包括急性淋巴细胞白血病和急性巨核细胞白血病（AMKL）。在过去四年里，我们对唐氏综合征相关的急性巨核细胞白血病的认识有了长足的进展。与其他儿童白血病一样，唐氏综合征相关的急性巨核细胞白血病在子宫内就已发病，在新生儿期可能表现为临床上明显的白血病前期状态，即暂时性骨髓增殖性疾病（TMD）。除了21号染色体三体之外，胎儿造血祖细胞在关键的巨核细胞-红系转录因子GATA1中获得N端截短突变。这些是TMD发生发展所需的最少事件。在大约30%的TMD患者中，进展为AMKL还需要其他尚未确定的（表观）基因突变。因此，唐氏综合征相关的TMD和AMKL为儿童白血病提供了一个独特的模型，其中白血病前期和白血病期是可以确定和区分的，从而能够分别研究白血病发生发展的不同阶段。这些发现对唐氏综合征相关的TMD和AMKL的临床管理具有重要意义，对儿童白血病的临床管理也具有更广泛的意义。
