Matarraz S, López A, Barrena S, Fernandez C, Jensen E, Flores J, Bárcena P, Rasillo A, Sayagues J M, Sánchez M L, Hernandez-Campo P, Hernandez Rivas J M, Salvador C, Fernandez-Mosteirín N, Giralt M, Perdiguer L, Orfao A
Servicio General de Citometría, Departamento de Medicina, Centro de Investigación del Cáncer, Instituto de Biología Molecular y Celular del Cáncer, CSIC-USAL, Universidad de Salamanca, Salamanca, Spain.
Leukemia. 2008 Jun;22(6):1175-83. doi: 10.1038/leu.2008.49. Epub 2008 Mar 13.
Occurrence of phenotypic abnormalities in CD34(+) hematopoietic progenitor and precursor cells (HPC) and their major B-cell and nonlymphoid compartments has been frequently reported in myelodysplastic syndromes (MDS). Here, we analyze for the first time the numerical and phenotypic abnormalities of different maturation-associated subsets of bone marrow (BM) CD34(+) HPC from 50 newly diagnosed MDS patients in comparison to normal/reactive BM (n=29). Our results confirm the existence of heterogeneously altered phenotypes among CD34(+) HPC from MDS and indicate that such variability depends both on the relative distribution of the different subsets of CD34(+) HPC committed into the different myeloid and B-lymphoid compartments, and their immunophenotype (for example, higher reactivity for CD117 and CD13 and lower expression of CyMPO, CD64 and CD65 on CD34(+) immature and neutrophil precursors), a clear association existing between the accumulation of CD34(+) HPC and that of immature CD34(+) HPC. Interestingly, expansion of erythroid- and neutrophil-lineage CD34(+) cells is detected in low-grade MDS at the expense of CD34(+) plasmacytoid dendritic cell and B-cell precursors, while expansion of immature CD34(+) precursors occurs in high-grade MDS. On the basis of the number and severity of the phenotypic abnormalities detected, a scoring system is proposed that efficiently discriminates between normal/reactive and MDS CD34(+) HPC, the mean score significantly increasing from low- to high-grade MDS.
在骨髓增生异常综合征（MDS）中，CD34(+)造血祖细胞和前体细胞（HPC）及其主要B细胞和非淋巴区室中表型异常的发生已被频繁报道。在此，我们首次分析了50例新诊断的MDS患者骨髓（BM）CD34(+) HPC不同成熟相关亚群的数量和表型异常，并与正常/反应性骨髓（n = 29）进行比较。我们的结果证实了MDS患者CD34(+) HPC中存在异质性改变的表型，并表明这种变异性既取决于分化为不同髓系和B淋巴细胞区室中的CD34(+) HPC不同亚群的相对分布，也取决于它们的免疫表型（例如，CD34(+)未成熟细胞和中性粒细胞前体细胞上CD117和CD13的反应性较高，而CyMPO、CD64和CD65的表达较低），CD34(+) HPC的积累与未成熟CD34(+) HPC的积累之间存在明显关联。有趣的是，在低级别MDS中检测到红系和中性粒细胞系CD34(+)细胞的扩增，以CD34(+)浆细胞样树突状细胞和B细胞前体细胞为代价，而在高级别MDS中则出现未成熟CD34(+)前体细胞的扩增。基于检测到的表型异常的数量和严重程度，我们提出了一种评分系统，该系统能够有效地区分正常/反应性和MDS的CD34(+) HPC，平均评分从低级别到高级别MDS显著增加。
