Apoptosis and neutrophils in the regulation of Ph-positive myeloid cell proliferation and differentiation ex vivo

Гринева, Н. И.; Akhlynina, T. V.; Тимофеев, A. M.; Герасимова, Л. П.; Schmarov, D. A.; Nydenova, N. M.; Манакова, Т. Е.; Sarycheva, Tatyana; Kovaleva, L G

doi:10.1134/s0026893313040043

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“…The regularities of the proliferation and differentiation of Ph + cells have already been studied [1–6]; the polynomial approximation of these curves is considered here, since they fail to obey either the logarithmic or exponential law, and the kinetic curves corresponding to these dependences have several maxima and minima ( Figs. 1–9 ).…”

Section: Resultsmentioning

confidence: 99%

“…The characteristics of the Ph + cells and CML patients from whose PB and BM the mononuclears were isolated are given in [2–5]. The types of bcr/abl mRNA (b3a2, b2a2 or e1a2) in the Ph + cells were determined by RT-PCR [2, 5]. …”

Section: Methodsmentioning

confidence: 99%

“…The degree of apoptosis and distribution of cultured Ph + cells over the phases of the cell cycle were analyzed cytofluorometrically [1–4] in the granulocyte gate on an EPICS-XL flow fluorimeter. Ph + cell samples (5,000 cells each) isolated from BM and PB in a Ficoll density gradient and the samples collected during the cultivation were centrifuged for 7 min at 600 g and 4 о С, washed with PBS, and fixed dropwise adding cooled 70% ethanol during 30 min at 4 о С.…”

Section: Methodsmentioning

confidence: 99%

“…The kinetic curves of the P/D efficiency index (the ratio between the neutrophil proliferation and maturation rates) were obtained as ratios between the accumulation of immature proliferating cells, P (blasts, promyelocytes, myelocytes), and the accumulation of neutrophils maturing without dividing, mature cells, D (metamyelocytes, bands and segments) according to [1–4]. …”

Section: Methodsmentioning

confidence: 99%

“…The proliferation rate is higher than the maturation rate at stage 1, whereas the maturation rate is higher at stage 2. The alternation of the stages and their rates maintains the optimal level of proliferation and differentiation efficiency in Ph + cells [1–4] and determines the wave-like regulation of these processes.…”

Section: Introductionmentioning

confidence: 99%

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Gene Expression upon Proliferation and Differentiation of Hematopoietic Cells with PH Chromosome ex vivo

et al. 2012

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The genesp53, mdm2, p21, c-myc,bcr/abl, bcr, bcl2, bax, and gapdh participate in the regulation of cell proliferation and differentiation, apoptosis and cell distribution for the cell cycle ex vivo in the Ph+cells of chronic myeloid leukemia containing the Ph chromosome andbcr/abloncogene. Expression of these genes correlates with regulation of cell proliferation and differentiation by alternating proliferation and maturation stages for three main Ph+cell types that occur under chronic myeloid leukemia. Thep53, p21, mdm2, and gapdh genes overexpress in active proliferating myeloid cells in the cell cycle S+ G2/M phases and when the phases are coincident with the proliferation stage. Expression of these genes decreases to a considerable level under alternation of the Ph+cell proliferation and maturation stages and whenever the expression is greatly diminished under significant neutrophil accumulation and especially under repeated alternation of the stages. In the course of neutrophil maturation, gene expression levels decrease in the range of gapdh > actin > c-myc, bcr/abl,p21 > p53 > bcl2 > bax.The expression levels of these genes in neutrophils are lower than those in myelocytes and lower by an order of magnitude than that in the cells with a prolonged proliferation stage. TheBcr/ablexpression gene under prolonged maturation and neutrophil accumulation is inhibited; however it is enhanced by 2–3 times for the proliferation stage with myelocyte accumulation. Minimalbcr/ablexpression is observed under overexpression ofp53, mdm2, p21, c-myc,as well as under cell maximum at the S and G2/M phases. Bcr/abloverexpression is observed under low expression of thep53, p21, mdm2genes. In the Ph+ cells with a high P/D efficiency index (5–20), overexpression of the genes in the range ofbcr> gapdh>bcr/abl, as well as a decreased expression of thep53, bcl2, mdm2, p21<< gapdh genes is observed for Ph+cells from the CML blast crisis and CML acceleration phase. Low control of cell proliferation and cell cycle by gene-regulators presumably promotesbcr/abloverexpression and activаtes the production ofbcr/abl+ cells. Apoptosis in the Ph+ cells is induced by expression of thebax > bcl2, р53, p21, c-myc andgapdhgenes. The blocking of Ph+cell apoptosis, neutrophil accumulation, and decrease in the expression of the p53, mdm2 and p21, c-myc,bcr/abl genes occur at the maturation stage.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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