[Apoptosis and proliferation in the bone marrow of chronic myeloproliferative disorders--biological and prognostic importance].
Apoptosis and proliferation are important regulators of normal development and homeostasis in the bone marrow. Therefore, dynamics of hematopoiesis is mainly defined by these two parameters. However, since only few data are available from previous studies, we performed a retrospective analysis to elucidate some aspects of this complex pathomechanism. A total of 400 patients with chronic myeloproliferative disorders (CMPDs) and corresponding reactive bone marrow lesions were enrolled into this study. Apoptosis was detected in bone marrow tissue by the ISEL-technique and topoisomerase II alpha expression was demonstrated by the monoclonal antibody Ki-S1. Furthermore, by determination of the proliferating-cell nuclear antigen labeling (PCNA) index, we were able to calculate the proportion of cells in the G2/M phase, because both nuclear antigens are expressed in different phases of the cell cycle. Patients with IMF, PV, and ET revealed a normal range of apoptosis, whereas in chronic myeloid leukemia (CML) a significant increase could be observed. On the other hand, IMF and PV were characterized by a raised proliferative activity. Dynamics of hematopoiesis was assessed by calculation of the so called hematopoietic turnover index. In CML and reactive lesions no alterations of this parameter were detectable, but IMF and PV showed a significant increase. Survival analysis disclosed a relevant worsening of life expectancy for patients with reduced apoptosis and proliferation. In conclusion, our in-situ results confirm and extend previous experimental data on hematopoietic cell kinetics. In this context, a greater regenerative capacity of hematopoiesis may be reflected by an increased rate of apoptosis and/or proliferation and therefore is associated with a more favorable outcome.
Kvasnicka
H M
HM
Zentrum für Pathologie der Universität zu Köln. hm.kvassnicka@uni-koeln.de
Thiele
J
J
D000911:Antibodies, Monoclonal; D017209:Apoptosis; D015415:Biomarkers; D001853:Bone Marrow / Q000473:pathology*; D002453:Cell Cycle; D002455:Cell Division; D002908:Chronic Disease; D004250:DNA Topoisomerases, Type II / Q000032:analysis; D016195:G2 Phase; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology*; D008938:Mitosis; D008940:Mitotic Index; D009196:Myeloproliferative Disorders / Q000473:pathology*; D009367:Neoplasm Staging; D011086:Polycythemia / Q000473:pathology; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D013922:Thrombocytosis / Q000473:pathology
D000911:Antibodies, Monoclonal; D015415:Biomarkers; D018809:Proliferating Cell Nuclear Antigen; D004250:DNA Topoisomerases, Type II