Wang Guang Ping, Qi Zhen Hua, Chen Fang Ping
Department of Hematology, Xiangya Hospital of Central South University, Changsha, Hunan 410008, China.
Med Hypotheses. 2008;70(1):122-7. doi: 10.1016/j.mehy.2007.04.017. Epub 2007 Jun 12.
Acute myeloid leukemia (AML) is characterized by the accumulation of immature myeloid cells in the bone marrow and the suppression of normal hematopoiesis, chemotherapy is currently the most used method to treat AML. The standard chemotherapy results in a more than 50% complete remission rate in AML patients. However, treatment with drugs such as anthracyclines is associated with severe side effects and a high incidence of relapse, the long-term survival of AML is poor. The success of the treatment of acute promyelocytic leukemia with all trans retinoic acid and chronic myeloid leukemia with imatinib mesylate (Gleevec) has led to increased efforts to look for agents for AML targeted therapy. But, most of presented targeted therapy agents do only direct some oncogenic molecules involved in the leukemogenesis of AML, their anti-leukemic efficacy is unsatisfied. Thus, novel therapeutic approaches are required. In recent years, a leukemia stem cells (LSCs) origin for AML has been demonstrated, and some unique immunophenotype and specific molecular features of LSCs have also been identified. With the technique development of Immunoliposomes (antibody-coupled liposomes) and the recombination of the variable regions of heavy and light chains and their integration into a single polypeptide that offer the possibility of using single-chain antibody variable region fragments (scFv) for targeting purposes, here we put the hypothesis that treatment of AML by targeting both LSCs and oncogenic molecule participated in AML pathogenesis, with LSCs-specific scFv-immunolipoplexes as a deliverer, might be possible. If successfully using this approach in practice, LSCs might be selectively eradicated and AML might be cured.
急性髓系白血病（AML）的特征是骨髓中未成熟髓系细胞的积累以及正常造血功能的抑制，化疗是目前治疗AML最常用的方法。标准化疗使AML患者的完全缓解率超过50%。然而，使用阿霉素等药物进行治疗会带来严重的副作用和高复发率，AML患者的长期生存率较低。全反式维甲酸治疗急性早幼粒细胞白血病以及甲磺酸伊马替尼（格列卫）治疗慢性髓系白血病的成功促使人们加大了寻找AML靶向治疗药物的力度。但是，大多数已提出的靶向治疗药物仅针对一些参与AML白血病发生的致癌分子，其抗白血病疗效并不理想。因此，需要新的治疗方法。近年来，已证实AML起源于白血病干细胞（LSCs），并且还确定了LSCs的一些独特免疫表型和特定分子特征。随着免疫脂质体（抗体偶联脂质体）技术的发展以及重链和轻链可变区的重组并整合为单一多肽，这为使用单链抗体可变区片段（scFv）进行靶向提供了可能性，在此我们提出一个假设，即有可能以LSCs特异性scFv免疫脂质复合物作为载体，通过靶向LSCs和参与AML发病机制的致癌分子来治疗AML。如果在实践中成功应用这种方法，LSCs可能会被选择性根除，AML可能会被治愈。
