Edahiro Yoko
Department of Hematology, Juntendo University School of Medicine.
Rinsho Ketsueki. 2023;64(9):970-980. doi: 10.11406/rinketsu.64.970.
The discovery of driver genes such as JAK2 in myeloproliferative neoplasms (MPN) led to a better understanding of MPN pathogenesis as a constitutive activation of the JAK/STAT signal. Following these findings, several types of JAK inhibitors have been developed. Ruxolitinib, a JAK1/2 inhibitor licensed for polycythemia vera and myelofibrosis, demonstrated efficacy in regulating hematocrit levels, lowering spleen volume, and relieving MPN-related symptoms. However, some patients with myelofibrosis are refractory to JAK inhibitors, and some are intolerant due to cytopenia. Furthermore, JAK inhibitors did not slow the progression of acute leukemia, indicating the need for new therapeutic methods for myelofibrosis. Novel medicines, including BCL inhibitor, MDM2 inhibitor, LSD1 inhibitor, PI3K inhibitor, BET inhibitor and telomerase inhibitor, are presently being evaluated in clinical studies for myelofibrosis with the potential to enhance clinical outcomes.
骨髓增殖性肿瘤（MPN）中JAK2等驱动基因的发现，使人们对MPN发病机制有了更好的理解，即JAK/STAT信号的组成性激活。基于这些发现，已开发出几种类型的JAK抑制剂。芦可替尼是一种被批准用于真性红细胞增多症和骨髓纤维化的JAK1/2抑制剂，在调节血细胞比容水平、降低脾脏体积以及缓解MPN相关症状方面显示出疗效。然而，一些骨髓纤维化患者对JAK抑制剂耐药，还有一些患者因血细胞减少而不耐受。此外，JAK抑制剂并未减缓急性白血病的进展，这表明需要针对骨髓纤维化开发新的治疗方法。包括BCL抑制剂、MDM2抑制剂、LSD1抑制剂、PI3K抑制剂、BET抑制剂和端粒酶抑制剂在内的新型药物目前正在骨髓纤维化的临床研究中进行评估，有望改善临床疗效。
