骨髓增生异常综合征集落形成细胞培养特征及其与非重型再生障碍性贫血的比较研究

Analysis of in vitro characteristics of colony-forming cells in myelodysplastic syndrome and compari- son with that in non-severe aplastic anemia

目的探讨骨髓增生异常综合征（MDS）患者体外集落形成细胞（CFC）培养特征及其与非重型再生障碍性贫血（NSAA）患者的异同。方法回顾性分析了初诊未治的155例MDS患者的EFC培养结果及其与其他相关实验室检查参数的相关性，并与初诊未治的122例NSAA患者体外CFC培养结果进行了比较分析。结果MDS患者红细胞爆式集落形成单位（BFU—E）中位数9（0～157）／10^5骨髓单个核细胞（BMMNC），红细胞集落形成单位（CFU-E）中位数30（0～625）／10^5BMMNC，粒一单该细胞集落形成单位（CFU—GM）中位数14（0—125）／10^5BMMNC，较正常参考值均显著减；66例（42．6％）仅BFU—E和（或）CFU—E低于正常下限，3例（1．9％）仅CFU—GM低于正常下限，70例（45．2％）BFU—E和（或）CFU—E且CFU．GM低于正常下限。MDS患者中集簇数同BFU—E、CFU—E及CFU．GM数均呈正相关（r值分别为0．415、0．338、0．642，P值均为0．000），同中性粒细胞碱性磷酸酶（N—ALP）阳性率和阳性积分均呈负相关（rm性率=-0．315，P=0．001；r日性积分=-0．257，P=0．006）。MDS组各类型集落中位数均明显高于NSAA组（BFU—E9对5／10^5BMMNC，P=0．017；CFU—E30对19．5／10^5BMMNC，P=0．023；CFU—GM14对10／10。BMMNC，P=0．003），两组内BFU—E和CFU—E均呈正相关（rMDS=0．712，P=0．000和rNSAA=0．757，P=0．000），MDS组相关度低于NSAA组（P〈0．05）。结论MDS起病初期造血祖细胞数量明显减少，且红系受累更为广泛而显著；BFU—E、CFU—E和CFU—GM能够反映出体内造血祖细胞水平但并非残存的正常造血克隆，集簇数代表了发育异常祖细胞克隆但不等同于白血病样原始细胞。

Objective To investigate in vitro characteristics of colony-forming cells （CFC） in patients with myelodysplastie syndrome （MDS） and to compare that in patients with non-severe aplastic anemia （NSAA）. Methods Data of in vitro CFC and correlation with other related laboratory tests in 155 newly di- agnosed MDS patients were analyzed retrospectively, and to compare with data of in vitro CFC in 122 newly diagnosed NSAA patients. Results Median number of burst-forming units-erythroid （ BFU-E ） was 9 （0 - 157 ）/105 bone marrow mononuclear cells （ BMMNC ）, colony forming unit-erythroid （ CFU-E ） 30 （ 0 - 425 ） / 105 BMMNC and colony forming unit-granulocytes/macrophages （CFU-GM） 14 （0 - 125 ）/105 BMMNC in pa- tients with MDS, being significantly lower than those in healthy control; number of BFU-E and/or CFU-E was lower than the lower limit of normal control in 66 cases （42.6%）, CFU-GM lower in 3 cases （ 1.9% ） and BFU-E and/or CFU-E with CFU-GM lower in 70 cases （45.2%）. Cluster/CFU-GM ratio was significantly lower in low blast group （MDS 〈 5% blast in bone marrow smear） than that in high blast group （MDS I〉5% blast） （0.65 vs 1.0, P = 0. 049）. In all MDS patients, cluster had positive correlation with each type ofCFC （r =0.415, 0. 338, 0. 642 for BFU-E, CFU-E, CFU-GM, respectively, P =0.000）, but had negative correlation with neutrophil alkaline phosphatase （N-ALP） positive rate and scores （rrate ~ --0. 315, P = 0.001 and r = -0.257, P =0. 006）. The median number of each type of CFC was significantly higher in MDS group than that in NSAA group （BFU-E 9 vs 5/105BMMNC, P = 0. 017; CFU-E 30 vs 19. 5/ 105BMMNC, P =0. 023 ; CFU-GM 14 vs 10/105BMMNC, P =0. 003, respectively）. Positive correlation be- tween BFU-E and CFU-E were revealed in both MDS and NSAA group （rMos = 0. 712, P = 0. 000 and rNsnA = O. 757, P = 0. 000）, with a lower correlation coefficient in MDS （ P 〈 0.05 ）. Conclusions Early onset MDS present markedly decreased hematopoietie progenitor cells （ HPC ） , and particularly in erythroid progenitors extensively and severely. The number of BFU-E, CFU-E and CFU-GM can reflect HPC number in vivo but not stand for normal hematopoietic clones, the number of clusters represent pathologic HPC clones but not exactly leukemic blasts.