Lessons From Pediatric MDS: Approaches to Germline Predisposition to Hematologic Malignancies.
Lessons From Pediatric MDS: Approaches to Germline Predisposition to Hematologic Malignancies.
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DOI：
10.3389/fonc.2022.813149
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发表时间：
2022
影响因子：
4.7
通讯作者：
Shimamura A
中科院分区：
文献类型：
--
作者：
Avagyan S;Shimamura A
小儿骨髓增生异常综合征（MDS）通常引起对血液恶性肿瘤的潜在生殖系易感性（在本文中称为生殖系易感性）的关注。随着基因检测的可用性，现在很明显，综合征的特点可能缺乏生殖系易感性的患者。许多遗传性病变的基础生殖系易感性也可能发生突变体细胞在新发MDS和白血病，使其至关重要的是，以区分其生殖系起源。对疑似生殖系易感性的验证可以为治疗考虑提供信息，指导治疗前和治疗后的监测，并允许家庭咨询。由于生殖系易感性导致的MDS的表现不限于儿童，并且跨越广泛的年龄范围。事实上，MDS的风险可能会随着年龄的增长而增加，在许多生殖系易感性条件下，并可能出现在儿童时期缺乏经典标志的成年人中。此外，与DDX41突变相关的生殖系易感性与老年人发病的MDS有关。虽然有较高比例的儿童MDS患者具有生殖系易感性，但成人患者中MDS诊断的数量越多，可能导致具有潜在生殖系易感性的患者总数越多。在这篇综述中，我们提出了一个评估所有年龄段MDS生殖系易感性的框架。我们讨论了个人和家族史，临床检查和实验室检查结果的特点，并整合基因测序结果，以协助诊断评估。我们解决的生殖系易感性的诊断对个人的影响，为他们的护理后MDS治疗，并为家庭成员。对具有生殖系易感性的MDS的研究为恶性血液病的发病机制和体细胞遗传拯救与疾病进展的机制提供了独特的见解。在成人患者中增加识别将告知医疗管理，并可能为预防或拦截恶性肿瘤提供潜在的机会。
Pediatric myelodysplastic syndromes (MDS) often raise concern for an underlying germline predisposition to hematologic malignancies, referred to as germline predisposition herein. With the availability of genetic testing, it is now clear that syndromic features may be lacking in patients with germline predisposition. Many genetic lesions underlying germline predisposition may also be mutated somatically in de novo MDS and leukemias, making it critical to distinguish their germline origin. The verification of a suspected germline predisposition informs therapeutic considerations, guides monitoring pre- and post-treatment, and allows for family counseling. Presentation of MDS due to germline predisposition is not limited to children and spans a wide age range. In fact, the risk of MDS may increase with age in many germline predisposition conditions and can present in adults who lack classical stigmata in their childhood. Furthermore, germline predisposition associated with DDX41 mutations presents with older adult-onset MDS. Although a higher proportion of pediatric patients with MDS will have a germline predisposition, the greater number of MDS diagnoses in adult patients may result in a larger overall number of those with an underlying germline predisposition. In this review, we present a framework for the evaluation of germline predisposition to MDS across all ages. We discuss characteristics of personal and family history, clinical exam and laboratory findings, and integration of genetic sequencing results to assist in the diagnostic evaluation. We address the implications of a diagnosis of germline predisposition for the individual, for their care after MDS therapy, and for family members. Studies on MDS with germline predisposition have provided unique insights into the pathogenesis of hematologic malignancies and mechanisms of somatic genetic rescue vs. disease progression. Increasing recognition in adult patients will inform medical management and may provide potential opportunities for the prevention or interception of malignancy.
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影响因子：
30.8
作者：
Cordeddu, Viviana;Di Schiavi, Elia;Pennacchio, Len A.;Ma'ayan, Avi;Sarkozy, Anna;Fodale, Valentina;Cecchetti, Serena;Cardinale, Alessio;Martin, Joel;Schackwitz, Wendy;Lipzen, Anna;Zampino, Giuseppe;Mazzanti, Laura;Digilio, Maria C.;Martinelli, Simone;Flex, Elisabetta;Lepri, Francesca;Bartholdi, Deborah;Kutsche, Kerstin;Ferrero, Giovanni B.;Anichini, Cecilia;Selicorni, Angelo;Rossi, Cesare;Tenconi, Romano;Zenker, Martin;Merlo, Daniela;Dallapiccola, Bruno;Iyengar, Ravi;Bazzicalupo, Paolo;Gelb, Bruce D.;Tartaglia, Marco
通讯作者：
Tartaglia, Marco
DOI：
10.1016/j.clml.2016.04.001
发表时间：
2016-07
期刊：
Clinical lymphoma, myeloma & leukemia
影响因子：
--
作者：
DiNardo CD;Bannon SA;Routbort M;Franklin A;Mork M;Armanios M;Mace EM;Orange JS;Jeff-Eke M;Churpek JE;Takahashi K;Jorgensen JL;Garcia-Manero G;Kornblau S;Bertuch A;Cheung H;Bhalla K;Futreal A;Godley LA;Patel KP
通讯作者：
Patel KP
影响因子：
3.6
作者：
Brown, Anna L.;Churpek, Jane E.;Godley, Lucy A.
通讯作者：
Godley, Lucy A.
影响因子：
11.4
作者：
Choi, JW;Yim, Y;Ito, M
通讯作者：
Ito, M
影响因子：
10.1
作者：
Donadieu, Jean;Lamant, Marie;Pasquet, Marlene
通讯作者：
Pasquet, Marlene