Oncology Research Unit, Oncology Hospital, Instituto Mexicano del Seguro Social, Mexico City, Mexico; Departamento de Biomedicina Molecular, CINVESTAV, México City, México.
Hospital para el Niño, Instituto Materno Infantil del Estado de México, México.
Arch Med Res. 2016 Nov;47(8):629-643. doi: 10.1016/j.arcmed.2016.12.004.
Childhood acute leukemias (AL) are characterized by the excessive production of malignant precursor cells at the expense of effective blood cell development. The dominance of leukemic cells over normal progenitors may result in either direct suppression of functional hematopoiesis or remodeling of microenvironmental niches, contributing to BM failure and AL-associated mortality. We undertook this study to investigate the contents and functional activity of hematopoietic stem/progenitor cells (HSPC) and their relationship to immune cell production and risk status in AL pediatric patients.
Multiparametric flow cytometry of BM aspirates was performed to classify AL on the basis of lineage and differentiation stages and to analyze HSPC and immune cell frequencies. Controlled co-culture systems were conducted to evaluate functional lineage potentials of primitive cells. Statistical correlations and inter-group significant differences were established.
Among 113 AL BM aspirates, 26.5% corresponded to ProB, 19.5% to PreB and 32% contain ProB and PreB differentiation stages, whereas nearly 9% of the cases were T- and 13% myeloid-lineage leukemias. We identified ProB-ALL as the subtype endowed with the highest relative contents of HSPC, whereas T-ALL and PreB-ALL showed a critically reduced size of both HSC and MLP compartments. Notably, lower cell frequencies of HSPC in ProB-ALL correlated to high-risk prognosis at disease debut.
HSPC abundance at initial diagnosis may aid to predict the clinical course of ALL and to identify high-risk patients. A clearer understanding of their population dynamics and functional properties in the leukemia setting will potentially pave the way for targeted therapies.
儿童急性白血病（AL）的特征是恶性前体细胞的过度产生，而有效血细胞的发育则受到损害。白血病细胞对正常祖细胞的优势可能导致功能性造血的直接抑制，或骨髓微环境龛的重塑，导致骨髓衰竭和与 AL 相关的死亡。我们进行这项研究，旨在调查 AL 患儿骨髓中造血干/祖细胞（HSPC）的含量和功能活性，及其与免疫细胞产生和风险状况的关系。
通过对骨髓抽吸物进行多参数流式细胞术，根据谱系和分化阶段对 AL 进行分类，并分析 HSPC 和免疫细胞的频率。进行受控共培养系统以评估原始细胞的功能谱系潜能。建立了统计相关性和组间显著性差异。
在 113 例 AL 骨髓抽吸物中，26.5%对应于 ProB，19.5%对应于 PreB，32%包含 ProB 和 PreB 分化阶段，而近 9%的病例为 T 系白血病，13%为髓系白血病。我们发现 ProB-ALL 是具有最高 HSPC 相对含量的亚型，而 T-ALL 和 PreB-ALL 则显示出 HSC 和 MLP 区室的临界缩小。值得注意的是，ProB-ALL 中 HSPC 的细胞频率较低与疾病初诊时的高危预后相关。
初始诊断时 HSPC 的丰度可能有助于预测 ALL 的临床过程，并识别高危患者。更清楚地了解它们在白血病环境中的群体动力学和功能特性，将有可能为靶向治疗铺平道路。
