Monreal Mariela B, Pardo Maria L, Pavlovsky Miguel A, Fernandez Isolda, Corrado Claudia S, Giere Isabel, Sapia Sandra, Pavlovsky Santiago
FUNDALEU (Foundation to Fight Leukemia) and Centro de Investigacion Clinica A. Ocampo, Buenos Aires, Argentina.
Cytometry B Clin Cytom. 2006 Mar;70(2):63-70. doi: 10.1002/cyto.b.20088.
Myelodysplastic syndromes (MDS) are clonal disorders affecting hematopoietic progenitor cells (HPC). Despite the relevance of clonal CD34+ cells in developing MDS, only few studies analyze the phenotype of this cell population. The aim of this study was to evaluate phenotypic changes on HPC in MDS that could reflect abnormalities in the differentiation process of stem cells.
We analyzed the expression of CD38 and HLA-DR on CD34+ cells by flow cytometry in 36 patients with MDS, as well as in healthy donors (n = 12) and patients with other hematological disorders: non-Hodgkin lymphomas and multiple myeloma, both in complete remission (CR) (n = 32); acute lymphoblastic leukemia in CR (n = 17); de novo acute myeloblastic leukemia (AML) at diagnosis (n = 22) and in CR (n = 37); and AML secondary to MDS at diagnosis (n = 19). Cases with available karyotype were grouped according to the International Prognostic Scoring System (IPSS).
Compared to normal BM, the fraction of immature HPC, characterized as CD34+bright, intermediate FSC/SSC, and CD38dim, was significantly increased in high risk MDS and secondary AML, but not in low risk MDS, (P < or = 0.001, P = 0.03, and P = 0.7). De novo AML showed decreased immature HPC. High numbers of immature HPC correlated with higher IPSS risk groups (P = 0.05) and showed significant impact on disease progression (P = 0.03).
Our study confirms that evaluation of CD38 expression pattern on HPC is an easy and reproducible test that allows evaluating the immature subset of progenitor cells. Increased immature HPC in high risk MDS and secondary AML may reflect blocked differentiation of CD34+ cells in these diseases.
骨髓增生异常综合征（MDS）是影响造血祖细胞（HPC）的克隆性疾病。尽管克隆性CD34+细胞在MDS发生过程中具有重要意义，但仅有少数研究分析了这一细胞群体的表型。本研究的目的是评估MDS中HPC的表型变化，这些变化可能反映干细胞分化过程中的异常。
我们通过流式细胞术分析了36例MDS患者、12例健康供者以及患有其他血液系统疾病患者的CD34+细胞上CD38和HLA-DR的表达，这些其他血液系统疾病包括：完全缓解（CR）的非霍奇金淋巴瘤和多发性骨髓瘤（n = 32）；CR的急性淋巴细胞白血病（n = 17）；初诊时的新发急性髓细胞白血病（AML）（n = 22）以及CR的AML（n = 37）；诊断时继发于MDS的AML（n = 19）。根据国际预后评分系统（IPSS）对有可用核型的病例进行分组。
与正常骨髓相比，高风险MDS和继发性AML中以CD34+bright、中等FSC/SSC和CD38dim为特征的未成熟HPC比例显著增加，而低风险MDS中未增加（P≤0.001、P = 0.03和P = 0.7）。新发AML显示未成熟HPC减少。大量未成熟HPC与较高的IPSS风险组相关（P = 0.05），并对疾病进展有显著影响（P = 0.03）。
我们的研究证实，评估HPC上CD38表达模式是一种简单且可重复的检测方法，可用于评估祖细胞的未成熟亚群。高风险MDS和继发性AML中未成熟HPC增加可能反映了这些疾病中CD34+细胞的分化受阻。
