Pamuk Gulsum E, Ehrlich Lori A
Office of Oncologic Diseases, Center for Drug Evaluation and Research-CDER, U.S. Food and Drug Administration, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA.
Cancers (Basel). 2024 Oct 26;16(21):3615. doi: 10.3390/cancers16213615.
Myeloid blast-phase chronic myeloid leukemia (MBP-CML) is a rare disease with a dismal prognosis. It is twice as common as lymphoid blast-phase CML, and its prognosis is poorer. Despite the success with tyrosine kinase inhibitors in the treatment of chronic-phase CML, the same does not hold true for MBP-CML. In addition to the Philadelphia chromosome, other chromosomal and molecular changes characterize rapid progression. Although some progress in elucidating the biology of MBP-CML has been made, there is need to discover more in order to develop more satisfactory treatment options. Currently, most common treatment options include tyrosine kinase inhibitors (TKIs) as monotherapy or in combination with acute myeloid leukemia-based intensive chemotherapy regimens. Some patients may develop resistance to TKIs via BCR-ABL1-dependent or BCR-ABL1-independent mechanisms. In this paper, we provide an overview of the biology of MBP-CML, the current treatment approaches, and mechanisms of resistance to TKIs. In order to improve treatment responses in these patients, more emphasis should be placed on understanding the biology of myeloid blastic transformation in CML and mechanisms of resistance to TKIs. Although patient numbers are small, randomized clinical trials should be considered.
髓系原始细胞期慢性髓系白血病(MBP-CML)是一种预后不佳的罕见疾病。它的发病率是淋巴系原始细胞期慢性髓系白血病的两倍,且预后更差。尽管酪氨酸激酶抑制剂在慢性期慢性髓系白血病的治疗中取得了成功,但在MBP-CML的治疗中情况并非如此。除了费城染色体外,其他染色体和分子变化也表征了疾病的快速进展。虽然在阐明MBP-CML的生物学特性方面已取得一些进展,但仍需要进一步探索,以开发更令人满意的治疗方案。目前,最常见的治疗方案包括酪氨酸激酶抑制剂(TKIs)单药治疗或与基于急性髓系白血病的强化化疗方案联合使用。一些患者可能通过BCR-ABL1依赖性或BCR-ABL1非依赖性机制对TKIs产生耐药性。在本文中,我们概述了MBP-CML的生物学特性、当前的治疗方法以及对TKIs的耐药机制。为了改善这些患者的治疗反应,应更加重视了解慢性髓系白血病髓系原始细胞转化的生物学特性以及对TKIs的耐药机制。尽管患者数量较少,但仍应考虑进行随机临床试验。