Salesi N, Bossone G, Della Longa G, Di Cocco B
Scuola di Specializzazione in Oncologia Medica, II Facoltà di Medicina e Chirurgia, Università degli Studi di Roma La Sapienza, Roma, Italy.
Minerva Med. 2003 Apr;94(2):71-6.
The therapy of chronic myeloid leukemia, characterized by the presence of the Philadelphia chromosome in the clonal hematopoietic stem cells, has changed dramatically in the last years with the development of a specific inhibitor of the BCR-ABL tyrosine kinase: tyrosine kinase inhibitor imatinib mesylate (formerly STI571, [Glivec]). Glivec selectively blocks cellular proliferation and induces apoptosis in Philadelphia chromosome-positive (Ph+) cells harbouring the Bcr-Abl tyrosine kinase. Clinical development of imatinib mesylate began with 3 large, multicenter, phase II trials. The majority (88%) of interferon-alpha-resistant or intolerant patients in chronic-phase CML, achieved a complete hematologic response to imatinib mesylate. More importantly, approximately half of the patients achieved a major cytogenetic response, a result historically associated with improved survival. Furthermore, 21% of patients in accelerated-phase CML and 13.5% of patients in blastic-phase CML (patient populations with typically poor prognosis before the advent of imatinib mesylate) achieved major cytogenetic responses.
慢性髓性白血病的治疗以克隆造血干细胞中存在费城染色体为特征，在过去几年中随着BCR-ABL酪氨酸激酶特异性抑制剂的开发发生了巨大变化：酪氨酸激酶抑制剂甲磺酸伊马替尼（原STI571，[格列卫]）。格列卫选择性地阻断细胞增殖，并在携带Bcr-Abl酪氨酸激酶的费城染色体阳性（Ph+）细胞中诱导凋亡。甲磺酸伊马替尼的临床开发始于3项大型多中心II期试验。慢性期慢性髓性白血病中大多数（88%）对α干扰素耐药或不耐受的患者对甲磺酸伊马替尼实现了完全血液学缓解。更重要的是，大约一半的患者实现了主要细胞遗传学缓解，这一结果在历史上与生存率提高相关。此外，加速期慢性髓性白血病患者中有21%以及急变期慢性髓性白血病患者中有13.5%（在甲磺酸伊马替尼出现之前通常预后较差的患者群体）实现了主要细胞遗传学缓解。
