Kinetics of bone marrow cell production in human acute and chronic myeloid leukemias

Dormer, Peter G.; Lau, B.; Wilmanns, W.

doi:10.1016/0145-2126(80)90082-x

Cited by 28 publications

(12 citation statements)

References 13 publications

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“…In AML, a population of primitive cells arrested at different stages of maturation, which may be defined by the FAB classification, dominates the bone marrow. According to cell kinetic studies a prevalent cell production rate is detectable in the myeloblastic compartment [3,17]. This in vitro finding is reflected by a significant increase in the PCNA labeling index in combination with normal ranges of apoptosis [57].…”

Section: Discussionmentioning

confidence: 99%

Hematopoietic turnover index in reactive and neoplastic bone marrow lesions: quantification by apoptosis and PCNA labeling

Thiele

Zirbes

Lorenzen

et al. 1997

Annals of Hematology

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In order to determine the dynamics of hematopoietic cell turnover, proliferative activity and incidence of apoptosis (programmed cell death) were evaluated in bone marrow trephine biopsies. Selection of patients (20 in each group) included in addition to a control group, idiopathic thrombocytopenia (ITP), reactive thrombocytosis (TH), secondary polycythemia-smokers' polyglobuly (PG), primary (essential-hemorrhagic) thrombocythemia (PTH), polycythemia vera (PV), and finally acute myeloid leukemia (AML). Apoptosis was demonstrated by the in situ end-labeling technique (ISEL) and proliferative activity by applying the monoclonal antibody PC10 raised against proliferating cell nuclear antigen (PCNA). To assess dynamic features of hematopoiesis, an index was calculated consisting of the ratio between PCNA-positive nuclei and the apoptotic cell fraction. This factor was termed the hematopoietic turnover index (HTI). Morphometric analysis revealed that the HTI was significantly increased in AML and PV. According to cell culture studies both disorders are characterized by either a prevalent proliferation of the myeloid or erythroid cell mass. On the other hand, PG, PTH, and TH showed no relevant enhancement of this index in comparison to the control specimen. In vitro experiment results are in keeping with the finding that PG and PTH are not associated with a significant expansion of the erythroid lineage (CFU-E). Similar to ITP and TH, in PTH megakaryocyte proliferation (CFU-MEG) is the predominant feature of cell turnover. Differences between PTH and TH are in line with the reduced in vitro formation of CFU-MEG in the latter disorder. In conclusion, our in situ study on turnover rates of the bone marrow in various neoplastic and reactive lesions extends previous experimental data on hematopoietic cell kinetics.

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Section: Discussionmentioning

confidence: 99%

Hematopoietic turnover index in reactive and neoplastic bone marrow lesions: quantification by apoptosis and PCNA labeling

Thiele

Zirbes

Lorenzen

et al. 1997

Annals of Hematology

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“…It is an aggressive disease that involves rapid growth of abnormal leukemic cells in the bone marrow, resulting in failure of production of normal blood cells [1]. FLT3 ( Fms-like tyrosine kinase 3 ) is a commonly mutated gene found in AML patients with the approximately 5–30% of the cases of AML [2].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of FLT3 Expression by Green Tea Catechins in FLT3 Mutated-AML Cells

Thanh

Yamagishi

et al. 2013

PLoS ONE

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Acute myeloid leukemia (AML) is a heterogeneous disease characterized by a block in differentiation and uncontrolled proliferation. FLT3 is a commonly mutated gene found in AML patients. In clinical trials, the presence of a FLT3-ITD mutation significantly correlates with an increased risk of relapse and dismal overall survival. Therefore, activated FLT3 is a promising molecular target for AML therapies. In this study, we have shown that green tea polyphenols including (−)-epigallocatechin-3-gallate (EGCG), (−)-epigallocatechin (EGC), and (−)-epicatechin-3-gallate (ECG) suppress the proliferation of AML cells. Interestingly, EGCG, EGC and ECG showed the inhibition of FLT3 expression in cell lines harboring FLT3 mutations. In the THP-1 cells harboring FLT3 wild-type, EGCG showed the suppression of cell proliferation but did not suppress the expression of FLT3 even at the concentration that suppress 100% cell proliferation. Moreover, EGCG-, EGC-and ECG-treated cells showed the suppression of MAPK, AKT and STAT5 phosphorylation. Altogether, we suggest that green tea polyphenols could serve as reagents for treatment or prevention of leukemia harboring FLT3 mutations.

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“…CML myeloid progenitors display normal mitotic indices, normal responses to colony-stimulating factors and do not proliferate faster than their normal counterparts (Stryckmans et al, 1976;Dormer et al, 1980;Koeffler and Golde, 1981;Strife and Clarkson, 1988). Hematopoietic cell population size is also regulated by apoptosis, for example hemopoetic colony stimulating factors suppress apoptosis (Williams, 1991;Greenberg, 1992), and thus the myeloid expansion seen in CML may be due to enhanced cell survival rather than excessive proliferation.…”

Section: Introductionmentioning

confidence: 99%

Downregulation of Bcr-Abl in K562 cells restores susceptibility to apoptosis: Characterization of the apoptotic death

et al. 1997

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We examined the susceptibility of a variety of human leukemic cell lines to the induction of apoptosis. K562, a chronic myelogenous leukemic cell line which expresses the bcr-abl fusion gene, was found to be extremely resistant to apoptosis, irrespective of the inducing agent. This resistance can be attributed to the deregulated Abl kinase activity of bcr-abl, as downregulation of its expression using antisense oligodeoxynucleotides targeted to the beginning of the abl sequence in this chimeric gene rendered these cells susceptible to cytotoxic drug-induced apoptosis. Examination of the morphological and biochemical features of apoptosis in K562 cells revealed the typical membrane blebbing and chromatin condensation associated with this form of cell death. In situ TdT-mediated end labeling of the DNA revealed the presence of strand breaks in the treated cells and field inversion gel electrophoresis revealed the presence of large 10 ± 50 kb fragments. However there was an absence of oligonucleosomal DNA fragmentation, whether or not Bcr-Abl was expressed. Thus, while inhibition of expression of Bcr-Abl renders K562 cells susceptible to apoptosis, the absence of oligonucleosomal DNA fragmentation in these cells is independent of the function of this molecule.

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Kinetics of bone marrow cell production in human acute and chronic myeloid leukemias

Cited by 28 publications

References 13 publications

Hematopoietic turnover index in reactive and neoplastic bone marrow lesions: quantification by apoptosis and PCNA labeling

Hematopoietic turnover index in reactive and neoplastic bone marrow lesions: quantification by apoptosis and PCNA labeling

Inhibition of FLT3 Expression by Green Tea Catechins in FLT3 Mutated-AML Cells

Downregulation of Bcr-Abl in K562 cells restores susceptibility to apoptosis: Characterization of the apoptotic death

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