Genthon A, Killian M, Mertz P, Cathebras P, Gimenez De Mestral S, Guyotat D, Chalayer E
Service d'hématologie clinique et de thérapie cellulaire, hôpital Saint-Antoine, AP-HP, Paris, France; Médecine Sorbonne université, Paris, France.
Service de médecine interne, hôpital Nord, CHU de Saint-Étienne, 42055 Saint-Étienne cedex 02, France.
Rev Med Interne. 2021 Feb;42(2):101-109. doi: 10.1016/j.revmed.2020.08.018. Epub 2020 Nov 23.
Myelofibrosis is a BCR-ABL1-negative chronic myeloproliferative neoplasm that includes primary myelofibrosis, post-polycythemia vera myelofibrosis, and post-essential thrombocythemia myelofibrosis. It is characterized by stem cell-derived clonal proliferation that is often, but not always, accompanied by somatic mutations, which are classified into driver mutations (JAK2, CALR, or MPL), subclonal mutations and fibrosis on bone marrow biopsy. Myelofibrosis commonly demonstrates splenomegaly, constitutional symptoms, anemia, thrombocytosis, or thrombocytopenia. Patients may also be asymptomatic. Complications as thromboembolic or hemorrhagic events can reveal the disease. Primary myelofibrosis is the least common myeloproliferative neoplasm but is associated with poor survival and acute leukemic transformation. In contrast to the significant progress made in understanding the disease's pathogenesis, treatment for myelofibrosis remains largely palliative. The JAK2 inhibitor, ruxolitinib is not sufficient in eliminating the underlying myeloid progenitor clone, as disease inevitably returns with therapy discontinuation. Allogeneic hematopoietic stem cell transplantation is the only therapeutic option that offers potential cure. The development of novel treatment strategies aimed at slowing or even reversing disease progression, prolonging patient survival and preventing evolution to blast-phase are still lacking.
骨髓纤维化是一种 BCR-ABL1 阴性的慢性骨髓增殖性肿瘤,包括原发性骨髓纤维化、真性红细胞增多症后骨髓纤维化和原发性血小板增多症后骨髓纤维化。其特征是干细胞来源的克隆性增殖,通常但并非总是伴有体细胞突变,这些突变可分为驱动突变(JAK2、CALR 或 MPL)、亚克隆突变以及骨髓活检显示的纤维化。骨髓纤维化通常表现为脾肿大、全身症状、贫血、血小板增多或血小板减少。患者也可能无症状。血栓栓塞或出血事件等并发症可能会揭示该疾病。原发性骨髓纤维化是最不常见的骨髓增殖性肿瘤,但与较差的生存率和急性白血病转化相关。与在理解该疾病发病机制方面取得的显著进展形成对比的是,骨髓纤维化的治疗在很大程度上仍然是姑息性的。JAK2 抑制剂鲁索替尼不足以消除潜在的髓系祖细胞克隆,因为随着治疗中断,疾病不可避免地会复发。异基因造血干细胞移植是唯一有可能治愈的治疗选择。目前仍缺乏旨在减缓甚至逆转疾病进展、延长患者生存期并防止进展至急变期的新型治疗策略。