Span L F, Dar S E, Shetty V, Mundle S D, Broady-Robinson L, Alvi S, Raymakers R A, de Witte T, Raza A
Rush Cancer Institute, RPSLMC, Chicago, IL, USA.
Leukemia. 1998 Nov;12(11):1685-95. doi: 10.1038/sj.leu.2401149.
Myelodysplastic syndromes (MDS) are highly proliferative bone marrow (BM) disorders where the primary lesion presumably affects a CD34+ early progenitor or stem cell. We investigated the proliferative characteristics of CD34+ cells of 33 untreated MDS patients (19 RA, 5 RARS, 7 RAEB, 2 RAEBt) and five patients with acute myeloid leukemia after MDS (sAML). All patients received a 1-h infusion of the thymidine analogue iodoor bromodeoxyuridine intravenously before a BM aspirate and biopsy was taken. A double-labeling immunohistochemistry technique by monoclonal anti-CD34 (QBend/10) and anti-IUdR/BrdU antibodies was developed and performed. By this technique we recognised CD34+ and CD34- cells actively engaged in DNA synthesis or not. As MDS evolves a significant increase occurred in the percentage of CD34+ cells of all myeloid cells (mean value: RA/RARS 1.67%; RAEB(t) 8.68%; sAML 23.83%) as well as in the percentage of proliferating CD34+ cells of all myeloid cells (RA/RARS 0.19%; RAEB(t) 0.43%; and sAML 3.30%). This was associated with a decreasing trend in the overall myeloid labeling index (LI: RA/RARS 25.8%, RAEB(t) 24.6% and sAML 21.5%). This decrease in overall myeloid LI is due to an exponential increase in the proportion of CD34+ cells of the proliferating compartment during MDS evolution (RA/RARS 0.35%, RAEB(t) 1.44% and sAML 11.98% of all S-phase cells). These CD34+ cells appeared to proliferate more slowly than their more mature CD34 negative counterparts, since we found a progressive increment in the mean total cell cycling time (Tc) of all myeloid cells during MDS progression (RA/RARS 39.8, RAEB(t) 45.2 and sAML 65.8 h). This study showed that during MDS evolution to sAML the CD34+ compartment develops a growth advantage leading to apparent expansion.
骨髓增生异常综合征（MDS）是高度增殖性的骨髓疾病，其原发性病变可能影响CD34 +早期祖细胞或干细胞。我们研究了33例未经治疗的MDS患者（19例RA、5例RARS、7例RAEB、2例RAEBt）以及5例MDS后急性髓系白血病（sAML）患者的CD34 +细胞的增殖特征。所有患者在进行骨髓穿刺和活检前，静脉输注胸腺嘧啶类似物碘脱氧尿苷或溴脱氧尿苷1小时。我们开发并实施了一种通过单克隆抗CD34（QBend/10）和抗IUdR/BrdU抗体的双标记免疫组织化学技术。通过该技术，我们识别出积极参与或未参与DNA合成的CD34 +和CD34 -细胞。随着MDS的进展，所有髓系细胞中CD34 +细胞的百分比（平均值：RA/RARS为1.67%；RAEB(t)为8.68%；sAML为23.83%）以及所有髓系细胞中增殖性CD34 +细胞的百分比（RA/RARS为0.19%；RAEB(t)为0.43%；sAML为3.30%）均显著增加。这与总体髓系标记指数（LI：RA/RARS为25.8%，RAEB(t)为24.6%，sAML为21.5%）的下降趋势相关。总体髓系LI的这种下降是由于在MDS进展过程中增殖区室中CD34 +细胞的比例呈指数增加（占所有S期细胞的RA/RARS为0.35%，RAEB(t)为1.44%，sAML为11.98%）。这些CD34 +细胞似乎比其更成熟的CD34阴性对应细胞增殖更慢，因为我们发现在MDS进展过程中所有髓系细胞的平均总细胞周期时间（Tc）逐渐增加（RA/RARS为39.8小时；RAEB(t)为45.2小时；sAML为65.8小时）。这项研究表明，在MDS向sAML演变过程中，CD34 +区室获得了生长优势，导致明显扩增。
