Kuliev Anver, Rechitsky Svetlana, Tur-Kaspa Ilan, Verlinsky Yury
Reproductive Genetics Institute, 2825 N. Halsted St., Chicago, IL 60657, USA.
Ann N Y Acad Sci. 2005;1054:223-7. doi: 10.1196/annals.1345.028.
There has been progress in the application of stem cell transplantation for treatment of an increasing number of severe congenital and acquired bone marrow disorders, currently restricted by the availability of human leukocyte antigen (HLA)-matched related donors. Preimplantation HLA typing has recently been introduced to improve the access to stem cell therapy for inherited bone marrow failures. Preimplantation genetic diagnosis (PGD) provides an option not only for avoiding an affected pregnancy with thalassemia and other inherited disorders but also for preselection of the HLA-compatible donors for affected siblings. Multiple short tandem repeat markers throughout the HLA region are applied for this purpose, allowing 100% accuracy of HLA typing, through picking up possible recombination in the HLA region, as well as the copy number of chromosome 6, which affect accuracy of preimplantation HLA typing. Present experience of preimplantation HLA typing includes preimplantation HLA typing in 180 cycles, 122 of which were done as part of PGD for Fanconi anemia, thalassemia, Wiscott-Aldrich syndrome, hyper-immunoglobulin M syndrome, hypohidrotic ectodermal dysplasia with immune deficiency, and X-linked adrenoleukodystrophy, and 58 for the sole purpose of HLA typing for leukemias and for aplastic and Diamond-Blackfan anemia. The applied method resulted in the accurate preselection and transfer of 100% HLA-matched embryos, yielding already three dozen clinical pregnancies and the birth of two dozen HLA-matched children to the siblings requiring stem cell transplantation. Successful therapy with HLA-matched stem cells, obtained from these PGD children, has been achieved already for Diamond-Blackfan anemia hypohidrotic ectodermal dysplasia with immune deficiency and thalassemia.
干细胞移植在治疗越来越多的严重先天性和后天性骨髓疾病方面取得了进展，目前受到人类白细胞抗原（HLA）匹配的相关供体可用性的限制。最近引入了植入前HLA分型，以改善遗传性骨髓衰竭患者获得干细胞治疗的机会。植入前基因诊断（PGD）不仅为避免地中海贫血和其他遗传性疾病的受影响妊娠提供了一种选择，而且还为受影响的兄弟姐妹预先选择HLA兼容的供体。为此目的，在整个HLA区域应用了多个短串联重复标记，通过检测HLA区域可能的重组以及6号染色体的拷贝数，允许HLA分型的准确率达到100%，而这两者都会影响植入前HLA分型的准确性。目前植入前HLA分型的经验包括180个周期的植入前HLA分型，其中122个作为范可尼贫血、地中海贫血、威斯科特-奥尔德里奇综合征、高免疫球蛋白M综合征、免疫缺陷性少汗性外胚层发育不良和X连锁肾上腺脑白质营养不良的PGD的一部分进行，另外58个仅用于白血病、再生障碍性贫血和先天性纯红细胞再生障碍性贫血的HLA分型。所应用的方法导致100% HLA匹配胚胎的准确预选和移植，已经产生了三十多个临床妊娠，并为需要干细胞移植的兄弟姐妹生下了二十多个HLA匹配的孩子。从这些PGD儿童获得的HLA匹配干细胞已经成功治疗了先天性纯红细胞再生障碍性贫血、免疫缺陷性少汗性外胚层发育不良和地中海贫血。
