title: Significance of CD34(-) and CD34(+) cell apoptosis and proliferation in bone marrow of patients with MDS and their impact on survival.
abstract: Alteration in the balance between cell apoptosis and proliferation is one of the pathophysiological mechanisms of the myelodysplastic syndromes (MDS). The question of whether the excessive apoptosis and/or proliferation predominantly involve the subset of progenitor cells (CD34(+) cells) or mature cells (CD34(-) cells) remains a controversial issue. This study was purpose to analyze the apoptosis and proliferation status of CD34(+) and CD34(-) cells in bone marrow (BM) of patients with MDS, to investigate the pathogenesis of MDS and to determine the relation of apoptosis and proliferation status of CD34(+) and CD34(-) cells with prognosis of MDS. The proportion of CD34(+) cells, the apoptosis and proliferation ratio (A/P) of CD34(+) and CD34(-) cells in BM of 40 patients with MDS, including 20 cases of high-risk MDS and 20 cases of low-risk MDS, and 10 normal persons as control were detected by flow cytometry; the influence of CD34(+) and CD34(-) cell apoptosis and proliferation levels on prognosis of MDS was evaluated by univariate and multivariate analysis of survival. The results showed that the proportion of CD34(+) cells in BM of high-risk MDS patients was significantly higher than that in BM of low-risk MDS patients and in normal BM [(1.92 ± 0.10)%, (1.09 ± 0.04)%, (1.03 ± 0.05)% respectively]. The apoptotic rates (AR) of both CD34(+) and CD34(-) cells were significantly higher in low-risk MDS [(54.75 ± 2.18)%, (80.36 ± 1.68)%] than in high-risk MDS [(24.87 ± 2.69)%, (23.12 ± 1.23)%] and in normal BM [(18.51 ± 2.74)%, (20.98 ± 2.21)%]. When compared between CD34(+) cells and CD34(-) cells in low-risk MDS, a greater AR of CD34(-) cells was found. However, the higher proliferative rate of CD34(+) cells was observed in high-risk MDS. In low-risk MDS, a higher A/P ratio was found in CD34(-) cells than in CD34(+) cells; whereas this ratio was equalized or inverted in high-risk MDS. In addition, the survival and prognosis correlated significantly with AR of CD34(+) cells. It is concluded that the early MDS is predominantly associated with excessive apoptosis of the mature CD34(-) cells. The proliferation rate of cells increases with the disease progression in MDS subsets, especially, in the subset of CD34(+) cells. Surprisingly, the apoptosis of CD34(+) cells may be a useful prognostic factor, and the inhibition of apoptotic mechanisms may induce the transformation of MDS to leukemia.
authors.affiliation: Department of Hematology, Cancer Hospital of Tianjin Medical University, Tianjin Key Laboratory of Tumor Prevention and Therapy, Tianjin 300060, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Xia
authors.forename: Qing
authors.initials: Q
authors.lastname: Guo
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Zhao
authors.forename: Hai-Feng
authors.initials: HF
authors.lastname: Zhao
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Han
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Xiao-Xiong
authors.initials: XX
authors.lastname: Wu
authors.forename: Yi-Zhuo
authors.initials: YZ
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018952:Antigens, CD34; D017209:Apoptosis; D001854:Bone Marrow Cells / Q000276:immunology / Q000473:pathology*; D016022:Case-Control Studies; D049109:Cell Proliferation; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000401:mortality / Q000473:pathology*; D011379:Prognosis; D015996:Survival Rate; D055815:Young Adult
chemical_list: D018952:Antigens, CD34