Hellström Lindberg Eva, Cavelier Lucia, Cammenga Jörg, Andersson Per-Ola, Fioretos Thoas, Rosenquist Richard
professor, överläkare, Karolinska institutet och Karolinska universitetssjukhuset.
docent, sjukhusgenetiker, Uppsala universitet och Akademiska sjukhuset, Uppsala.
Lakartidningen. 2021 May 10;118:20186.
Precision diagnostics and therapy have been implemented rather early in clinical hematology due to the easy accessibility of blood and bone marrow, allowing not only for consecutive genetic analysis at diagnosis, remission and relapse, but also for culturing these cells and testing new drugs in vitro. One contributing factor has also been the relatively low number of »driver« mutations in hematologic malignancies and that some of them are gain of function mutations that are relatively easy to target by drugs. Examples of this development are ABL1-, JAK2-, and FLT3-inhibitors for the treatment of chronic myeloid leukemia, myeloproliferative neoplasms, and acute myeloid leukemia, respectively. More recently, gene panel sequencing has been introduced in clinical routine to identify genetic alterations with diagnostic, prognostic and predictive impact, and more sensitive techniques to monitor minimal residual disease are emerging. Whole genome and transcriptome sequencing are currently evaluated as the next diagnostic tool. Finally, a large number of targeted therapies are currently under development and/or undergoing clinical trials.
由于血液和骨髓易于获取,精准诊断和治疗在临床血液学中很早就得以实施,这不仅使得在诊断、缓解期和复发期能够进行连续的基因分析,还能培养这些细胞并在体外测试新药。促成这一情况的一个因素是血液系统恶性肿瘤中“驱动”突变的数量相对较少,而且其中一些是功能获得性突变,相对容易被药物靶向。这一发展的实例包括分别用于治疗慢性髓性白血病、骨髓增殖性肿瘤和急性髓性白血病的ABL1抑制剂、JAK2抑制剂和FLT3抑制剂。最近,基因panel测序已被引入临床常规操作,以识别具有诊断、预后和预测意义的基因改变,并且正在出现更敏感的监测微小残留病的技术。全基因组和转录组测序目前正在作为下一个诊断工具进行评估。最后,大量的靶向治疗目前正在研发中和/或正在进行临床试验。