Department of Internal Medicine, Division of Hematology, The Ohio State University, Columbus, OH 43210, USA.
Department of Biomedical Informatics, The Ohio State University, Columbus, OH 43210, USA.
Nutrients. 2023 Dec 18;15(24):5138. doi: 10.3390/nu15245138.
Chronic lymphocytic leukemia (CLL) is a disease characterized by the accumulation of mature CD19CD5CD23 B cells in the bloodstream and in lymphoid organs. It usually affects people over 70 years of age, which limits the options for treatments. The disease is typically well-managed, but to date is still incurable. Hence, the need for novel therapeutic strategies remains. Nurse-like cells (NLCs) are major components of the microenvironment for CLL, supporting tumor cell survival, proliferation, and even drug resistance. They are of myeloid lineage, guided toward differentiating into their tumor-supportive role by the CLL cells themselves. As such, they are analogous to tumor-associated macrophages and represent a major therapeutic target. Previously, it was found that a mushroom extract, Active Hexose-Correlated Compound (AHCC), promoted the death of acute myeloid leukemia cells while preserving normal monocytes. Given these findings, it was asked whether AHCC might have a similar effect on the abnormally differentiated myeloid-lineage NLCs in CLL. CLL-patient PBMCs were treated with AHCC, and it was found that AHCC treatment showed a direct toxic effect against isolated CLL cells. In addition, it significantly reduced the number of tumor-supportive NLCs and altered their phenotype. The effects of AHCC were then tested in the Eµ-TCL1 mouse model of CLL and the Mll Flt3 model of AML. Results showed that AHCC not only reduced tumor load and increased survival in the CLL and AML models, but it also enhanced antitumor antibody treatment in the CLL model. These results suggest that AHCC has direct and indirect effects against CLL and that it may be of benefit when combined with existing treatments.
慢性淋巴细胞白血病（CLL）是一种以血液和淋巴器官中成熟的 CD19CD5CD23 B 细胞积累为特征的疾病。它通常发生在 70 岁以上的人群中，这限制了治疗的选择。这种疾病通常可以得到很好的控制，但迄今为止仍然无法治愈。因此，仍然需要新的治疗策略。类淋巴样细胞（NLCs）是 CLL 微环境的主要组成部分，支持肿瘤细胞的存活、增殖，甚至耐药性。它们是髓系细胞，由 CLL 细胞自身引导分化为支持肿瘤的作用。因此，它们类似于肿瘤相关巨噬细胞，是一个主要的治疗靶点。以前发现，一种蘑菇提取物，活性己糖相关化合物（AHCC），在保留正常单核细胞的同时促进急性髓系白血病细胞的死亡。鉴于这些发现，人们询问 AHCC 是否可能对 CLL 中异常分化的髓系 NLC 具有类似的作用。用 AHCC 处理 CLL 患者的 PBMC，发现 AHCC 治疗对分离的 CLL 细胞具有直接毒性作用。此外，它还显著减少了支持肿瘤的 NLC 数量并改变了它们的表型。然后在 CLL 的 Eµ-TCL1 小鼠模型和 AML 的 Mll Flt3 模型中测试了 AHCC 的作用。结果表明，AHCC 不仅减少了 CLL 和 AML 模型中的肿瘤负荷并提高了存活率，而且还增强了 CLL 模型中的抗肿瘤抗体治疗效果。这些结果表明，AHCC 对 CLL 具有直接和间接作用，与现有治疗方法联合使用可能会有获益。
