APPARENT EXPANSION OF CD34(-LEUKEMIA() CELLS DURING THE EVOLUTION OF MYELODYSPLASTIC SYNDROMES TO ACUTE MYELOID)

Myelodysplastic syndromes (MDS) are highly proliferative bone marrow ( BM) disorders where the primary lesion presumably affects a CD34(+) ea rly progenitor or stem cell. We investigated the proliferative charact eristics 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 anal ogue 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 dev eloped and performed. By this technique we recognised CD34(+) and CD34 (-) cells actively engaged in DNA synthesis or not. As MDS evolves a s ignificant 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 my eloid cells (RA/RARS 0.19%; RAEB(t) 0.43%; and sAML 3.30%). This was a ssociated with a decreasing trend in the overall myeloid labeling inde x (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 evolutio n (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 mo re mature CD34 negative counterparts, since we found a progressive inc rement 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). T his study showed that during MDS evolution to sAML the CD34(+) compart ment develops a growth advantage leading to apparent expansion.