Aguiñiga-Sanchez Itzen, Ledesma-Martínez Edgar, Lara-Castañeda Jose Luis, Melendez-Ibarra Frida, Weiss-Steider Benny, Soto-Cruz Isabel, Fajardo-Orduña Guadalupe, Santiago-Osorio Edelmiro
Hematopoiesis and Leukemia Laboratory, Research Unit on Cell Differentiation and Cancer, Faculty of High Studies Zaragoza, National Autonomous University of Mexico, Mexico City, Mexico.
Department of Biomedical Sciences, School of Medicine, Faculty of High Studies Zaragoza, National Autonomous University of Mexico, Mexico City, Mexico.
Cancer Diagn Progn. 2022 Jul 3;2(4):496-502. doi: 10.21873/cdp.10133. eCollection 2022 Jul-Aug.
BACKGROUND/AIM: Although acute myeloid leukemia (AML) has traditionally been considered an oncological emergency and initiation of therapy is believed to be crucial to minimizing disease-related morbidity and mortality, it has also been suggested that a certain delay in treatment has no negative consequences in terms of response, early mortality, or survival. We aimed to determine the effect of administration of sodium caseinate (SC), a salt of casein, the main milk protein, with cytarabine or with daunorubicin on survival in mice with well-established leukemia.
To assay the time of establishment of leukemia in the bone marrow, Balb/c mice were inoculated with 2.5×10 WEHI-3 cells/mouse and after 3, 6 and 9 days were euthanized. Bone marrow mononuclear cells (BM-MNCs) of the femur were obtained and cultured for 120 h with or without rmIL-3 and cell proliferation was evaluated by the crystal violet technique. Then, the effect of administrating SC-cytarabine or SC-daunorubicin on survival rates of mice with well-established leukemia was assayed. Another group of Balb/c mice was inoculated with WEHI-3 cell and after 10 days mice were treated with SC-cytarabine or SC-daunorubicin for 40 days. Survival rates were recorded daily and in surviving mice, the prevalence of bone marrow proliferation after treatment was assayed by the crystal violet technique.
The assay on the time of establishment of leukemia shows that in 9 days leukemia cells accumulate in the bone marrow in sufficient quantities to sustain an in vitro culture in the absence of growth factors, and we, thus, used this as a criterion of well-established leukemia. When mice with a burden of leukemic cells of more than 9 days were treated with SC-cytarabine or SC-daunorubicin, this resulted in 55% survival for both treatments, and the proliferation assays showed that the bone marrow retained its normal proliferation capacity.
SC-cytarabine or SC-daunorubicin treatment prolonged the survival rate of Balb/c mice with a burden of well-established leukemia, and there was no negative impact on bone marrow functionality; however, SC-cytarabine or SC-daunorubicin combination options need to be sought to increase survival beyond 40 days.
背景/目的：尽管急性髓系白血病（AML）传统上被视为一种肿瘤急症，且人们认为开始治疗对于将疾病相关的发病率和死亡率降至最低至关重要，但也有人提出，在治疗上有一定延迟在反应、早期死亡率或生存率方面并无负面影响。我们旨在确定酪蛋白酸钠（SC）（一种主要乳蛋白酪蛋白的盐）与阿糖胞苷或柔红霉素联合给药对已确诊白血病小鼠生存率的影响。
为测定骨髓中白血病形成的时间，给Balb/c小鼠每只接种2.5×10⁶个WEHI-3细胞，在3、6和9天后实施安乐死。获取股骨的骨髓单个核细胞（BM-MNCs），在有或无重组人白细胞介素-3（rmIL-3）的情况下培养120小时，并通过结晶紫技术评估细胞增殖情况。然后，测定给予SC-阿糖胞苷或SC-柔红霉素对已确诊白血病小鼠生存率的影响。另一组Balb/c小鼠接种WEHI-3细胞，10天后用SC-阿糖胞苷或SC-柔红霉素治疗40天。每天记录生存率，对于存活的小鼠，通过结晶紫技术测定治疗后骨髓增殖的发生率。
白血病形成时间的测定表明，在9天时白血病细胞在骨髓中积累到足够数量，足以在无生长因子的情况下维持体外培养，因此，我们将此作为已确诊白血病的标准。当用SC-阿糖胞苷或SC-柔红霉素治疗白血病细胞负荷超过9天的小鼠时，两种治疗方法的生存率均为55%，增殖分析表明骨髓保留了其正常增殖能力。
SC-阿糖胞苷或SC-柔红霉素治疗延长了已确诊白血病负荷的Balb/c小鼠的生存率，且对骨髓功能没有负面影响；然而，需要寻求SC-阿糖胞苷或SC-柔红霉素的联合方案，以使生存期超过40天。
