Okamoto Yasuhiro
Department of Pediatrics, Kagoshima University School of Medical and Dental Science.
Rinsho Ketsueki. 2021;62(10):1465-1473. doi: 10.11406/rinketsu.62.1465.
In an analysis of 653 cases of acute lymphoblastic leukemia associated with Down syndrome (DS-ALL) collected from clinical research groups worldwide, the 8-year disease-free survival for DS-ALL was 64%, which was worse than the 81% for non-DS-ALL during the same period. This could be because DS-ALL has less hyperdiploidy and ETV6-RUNX1 abnormalities, which have a favorable prognosis, more Ph-like ALL, which has a poor prognosis, as well as more adverse deaths due to infectious complications. It has been reported that optimizing the treatment intensity using minimal residual disease and by strengthening the measures against adverse effects improve the treatment outcome of DS-ALL. The incidence of DS-ALL is reported to be 20 times higher than that of non-DS-ALL. The mechanism is believed to be through proliferation of the lymphoid system caused by HMGN1 on chromosome 21 as well as activation of JAK-STAT and proliferation of ALL cells caused by overexpression of CRLF2, such as P2RY8-CRLF2 fusion. The CRLF2 abnormality is found in 30-60% of DS-ALL cases. In the future, treatment of CRLF2, targeting JAKs downstream of CRLF2, and administration of blinatumomab or CAR-T therapy will be incorporated into DS-ALL treatment.
在一项对全球临床研究小组收集的653例与唐氏综合征相关的急性淋巴细胞白血病（DS-ALL）病例的分析中，DS-ALL的8年无病生存率为64%，低于同期非DS-ALL的81%。这可能是因为DS-ALL中具有良好预后的高倍体和ETV6-RUNX1异常较少，预后较差的Ph样ALL较多，以及感染并发症导致的不良死亡较多。据报道，利用微小残留病优化治疗强度并加强对抗不良反应的措施可改善DS-ALL的治疗结果。据报道，DS-ALL的发病率比非DS-ALL高20倍。其机制被认为是通过21号染色体上的HMGN1引起淋巴系统增殖，以及CRLF2过表达（如P2RY8-CRLF2融合）导致JAK-STAT激活和ALL细胞增殖。在30%-60%的DS-ALL病例中发现CRLF2异常。未来，针对CRLF2下游JAKs的治疗以及blinatumomab或CAR-T疗法的应用将纳入DS-ALL治疗。
