新技术的出现使更频繁地识别骨髓增生异常综合征(MDS)和急性白血病(AL)的遗传易感性成为可能。目前最常见和最有特点的是CEBPA突变,RUNX1、GATA2、ETV6和DDX41,在存在这些具有高等位基因频率的突变之一的情况下,或在个人或家族史提示血液异常的情况下,如非免疫性血小板减少症,建议寻找遗传性血液系统恶性肿瘤(HHM)的可能性。的确,对这些HHM的早期识别可以更好地适应患者及其亲属的管理,因为异基因造血干细胞移植(HSCT)经常被提出用于这些病理。根据目前的数据,除了GATA2突变,突变的体质或体细胞性质似乎并不影响血液病的预后。因此,同种异体移植物的适应症将根据通常的标准确定。然而,在寻找家庭捐赠者时,重要的是要确保捐赠者没有遗传性疾病。为了保证在短时间内进行HSC同种异体移植的可能性,可能有必要启动平行程序以寻找无关的供体.鉴于在这种情况下HSC移植方式的信息有限,重要的是评估疾病的获益/风险以及决定条件处理类型(清髓性或降低强度)的程序.鉴于中期和长期继发性癌症风险的经验有限,建议降低强度调理可能是合适的,如在更好表征的综合征性血液系统疾病如范可尼贫血或端粒疾病的情况下。总之,更频繁地唤起HHM似乎很重要,特别是在有家族史的情况下,某些突变或持续性血液异常,为了讨论HSC同种异体移植的具体模式,特别是在寻找捐助者和评估程序的某些方式方面,比如调理。应该注意的是,HHM的发现,特别是如果同种异体HSC移植的迹象被保留,将提高伦理和心理的考虑,不仅为病人,还有他的家人.涉及分子生物学家的多学科方法,遗传学家,血液学家和心理学家是必不可少的。
The advent of new technologies has made it possible to identify genetic predispositions to myelodysplastic syndromes (MDS) and acute leukemias (AL) more frequently. The most frequent and best characterized at present are mutations in CEBPA, RUNX1, GATA2, ETV6 and DDX41 and, either in the presence of one of these mutations with a high allelic frequency, or in the case of a personal or family history suggestive of blood abnormalities such as non-immune thrombocytopenia, it is recommended to look for the possibility of a hereditary hematological malignancy (HHM). Indeed, early recognition of these HHMs allows better adaptation of the management of patients and their relatives, as allogeneic hematopoietic stem cell transplantation (HSCT) is very often proposed for these pathologies. According to current data, with the exception of the GATA2 mutation, the constitutional or somatic nature of the mutations does not seem to influence the prognosis of hematological diseases. Therefore, the indication for an allograft will be determined according to the usual criteria. However, when searching for a family donor, it is important to ensure that there is no hereditary disease in the donor. In order to guarantee the possibility of performing the HSC allograft within a short period of time, it may be necessary to initiate a parallel procedure to find an unrelated donor. Given the limited information on the modalities of HSC transplantation in this setting, it is important to assess the benefit/risk of the disease and the procedure to decide on the type of conditioning (myeloablative or reduced intensity). In view of the limited experience with the risk of secondary cancers in the medium and long-term, it may be appropriate to recommend reduced intensity conditioning, as in the case of better characterized syndromic hematological diseases such as Fanconi anemia or telomere diseases. In summary, it seems important to evoke HHM more frequently, particularly in the presence of a family history, certain mutations or persistent blood abnormalities, in order to discuss the specific modalities of HSC allografting, particularly with regard to the search for a donor and the evaluation of certain modalities of the procedure, such as conditioning. It should be noted that the discovery of HHM, especially if the indication of an allogeneic HSC transplant is retained, will raise ethical and psychological considerations not only for the patient, but also for his family. A multidisciplinary approach involving molecular biologists, geneticists, hematologists and psychologists is essential.