Apoptotic Changes Precede Mitochondrial Dysfunction in Red Cell‐type Pyruvate Kinase Mutant Mouse Erythroleukemia Cell Lines

Aisaki, Ken‐ichi; Kanno, Hitoshi; Oyaizu, Naoki; Hara, Yukichi; Shiro, Motoo; Ikawa, Yoji

doi:10.1111/j.1349-7006.1999.tb00730.x

Cited by 8 publications

(7 citation statements)

References 30 publications

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“…Previously, we have demonstrated that an R-PK-deficient Friend erythroleukemia cell line (SLC cells), which was established from Pk-1slc mice [23], underwent apoptosis during routine passage [24]. Isozyme analysis showed that R-PK activity was almost diminished, while another isozyme, M 2 -PK, was not affected.…”

Section: Discussionmentioning

confidence: 99%

Ineffective erythropoiesis in the spleen of a patient with pyruvate kinase deficiency

et al. 2003

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In this study, possible adverse effects of pyruvate kinase (PK) deficiency on the maturation of erythroid progenitors were investigated. A 4-year-old Japanese girl with severe PK deficiency underwent splenectomy to reduce her need for blood transfusions. The spleen was examined a histologically, and the hematopoietic progenitors in the spleen were assayed to evaluate the extramedullary hematopoiesis of this PK-deficient subject. The number of hematopoietic progenitors including CFU-GM, BFU-E and CFU-GEMM in the spleen of the PK-deficient patient was much higher than those found in control spleens, indicating enhanced extramedullary hematopoiesis. TUNEL assay demonstrated apoptotic cells in the splenic red pulp of the PK-deficient patient. The expression of 7A6 antigen was detected in cells isolated from spleen and in cells cultured in vitro, but only in those cells that were positive for glycophorin A. These results provide evidence that the metabolic disturbances in PK deficiency affect not only the survival of red cells but also the maturation of erythroid progenitors, which results in premature cell death, i.e., apoptosis. Am. J. Hematol. 74:68-72, 2003.

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Section: Discussionmentioning

confidence: 99%

Ineffective erythropoiesis in the spleen of a patient with pyruvate kinase deficiency

et al. 2003

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“…The di erentiation could also be demonstrated by the increase in the level of b-globin mRNA and in the extent of staining with erythroid cell-speci®c monoclonal antibody, TER-119 (Ikuta et al, 1990;Aisaki et al, 1999) (Figure 3). …”

Section: Effects Of Ras Mutants On Erythroid Differentiation Of Skt6 mentioning

confidence: 91%

Induction of erythroid differentiation by inhibition of Ras/ERK pathway in a Friend murine leukemia cell line

et al. 2000

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The role of Ras and MAP kinases (MAPKs) in the regulation of erythroid di erentiation was studied using a cell line (SKT6) derived from Friend virus (Anemic strain)-induced murine erythroleukemia. This cell line undergoes di erentiation in vitro in response to erythropoietin (EPO) or other chemical inducers such as dimethylsulfoxide (DMSO). When a constitutively active ras mutant (ras12V) was expressed in SKT6 cells, EPO-induced di erentiation was inhibited. Conversely, a dominant negative ras mutant (ras17N) induced di erentiation even in the absence of EPO, suggesting that the basal Ras activity is essential for the maintenance of the undi erentiated phenotype and proliferative potential in this cell line. Rapid inactivation of ERK was observed after expression of ras17N. Slow but signi®cant inactivation of ERK was also observed during EPOinduced di erentiation. Furthermore, overexpression of a constitutively active mutant of ERK-activating kinase (MAPKK) was found to suppress erythroid di erentiation, while pharmacological inhibition of MAPKK induced di erentiation. These ®ndings suggest that down-regulation of Ras/ERK signaling pathway may be an essential event in EPO-induced erythroid di erentiation in this system. Oncogene (2000) 19, 1500 ± 1508.

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“…The mechanism responsible for this effect remains unclear; however, Aisaki et al reported spontaneous apoptotic changes in a red cell-type-PK-de®cient murine erythroleukemia cell line with no mitochondrial dysfunction, 16 while Shim et al Figure 8. Culture of TF-1 cells with CPL results in DNA ladders.…”

Section: Discussionmentioning

confidence: 99%

Effects of cyclic polylactate (CPL) on the growth of cloned leukemic cellsin vitro

et al. 2000

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Apoptotic Changes Precede Mitochondrial Dysfunction in Red Cell‐type Pyruvate Kinase Mutant Mouse Erythroleukemia Cell Lines

Cited by 8 publications

References 30 publications

Ineffective erythropoiesis in the spleen of a patient with pyruvate kinase deficiency

Ineffective erythropoiesis in the spleen of a patient with pyruvate kinase deficiency

Induction of erythroid differentiation by inhibition of Ras/ERK pathway in a Friend murine leukemia cell line

Effects of cyclic polylactate (CPL) on the growth of cloned leukemic cellsin vitro

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