Apparent expansion of CD34+ cells during the evolution of myelodysplastic syndromes to acute myeloid leukemia

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 BARS, 7 RAEB, 2 RAEBt) and five patients with acute myeloid leukemia after MDS (sAML). Ail patients received a I-h infusion of the thymidine analogue iodo- or 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 (T-c) 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.