title: Apparent expansion of CD34+ cells during the evolution of myelodysplastic syndromes to acute myeloid leukemia.
abstract: 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.
authors.affiliation: Rush Cancer Institute, RPSLMC, Chicago, IL, USA.
authors.forename: L F
authors.initials: LF
authors.lastname: Span
authors.forename: S E
authors.initials: SE
authors.lastname: Dar
authors.forename: V
authors.initials: V
authors.lastname: Shetty
authors.forename: S D
authors.initials: SD
authors.lastname: Mundle
authors.forename: L
authors.initials: L
authors.lastname: Broady-Robinson
authors.forename: S
authors.initials: S
authors.lastname: Alvi
authors.forename: R A
authors.initials: RA
authors.lastname: Raymakers
authors.forename: T
authors.initials: T
authors.lastname: de Witte
authors.forename: A
authors.initials: A
authors.lastname: Raza
mesh_terms: D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000276:immunology*; D005260:Female; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D007951:Leukemia, Myeloid / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000473:pathology*; D016196:S Phase
chemical_list: D018952:Antigens, CD34