High Bad and Bax mRNA expression correlate with negative outcome in acute myeloid leukemia (AML)

Köhler, Thomas; Schill, Catherine; Deininger, MW; Krahl, R.; Borchert, Silke; Hasenclever, Dirk; Leiblein, Sabine; Wagner, Oswald; Niederwieser, Dietger

doi:10.1038/sj.leu.2402340

Cited by 66 publications

(45 citation statements)

References 45 publications

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“…Sizes of PCR products were: CXCR5 318 bp; CXCL13 158 bp and CD18 372 bp. Glyceraldehyde 3-phosphatase dehydrogenase (GAPDH) transcripts were measured using a ready-to-use quantitative PCR test kit (Roboscreen Gesellschaft fü r Molekulare Biotechnologie, Leipzig, Germany) as previously described (26).…”

Section: Real-time Pcrmentioning

confidence: 99%

The role of CXCR5 and its ligand CXCL13 in the compartmentalization of lymphocytes in thyroids affected by autoimmune thyroid diseases

Aust

Sittig

Becherer

et al. 2004

European Journal of Endocrinology

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Objective: Graves' disease (GD) and Hashimoto's thyroiditis (HT) are characterized by lymphocytic infiltrates partly resembling secondary lymphoid follicles in the thyroid. CXCR5 and its ligand CXCL13 regulate compartmentalization of B-and T-cells in secondary lymphoid organs. The aim of the study was to elucidate the role of this chemokine receptor -ligand pair in thyroid autoimmunity. Methods: Peripheral blood and thyroid-derived lymphocyte subpopulations were examined by flow cytometry for CXCR5. CXCR5 and CXCL13 cDNA were quantified in thyroid tissues by real-time RT-PCR. Results: We found no differences between the percentages of peripheral blood CXCR5þ T-and B-cells in GD patients (n ¼ 10) and healthy controls (n ¼ 10). In GD patients, the number of memory CD4 þ cells expressing CXCR5 which are functionally characterized as follicular B helper T-cells is higher in thyroidderived (18^3%) compared with peripheral blood T-lymphocytes (8^2%). The highest CXCL13 mRNA levels were found in HT (n ¼ 2, 86.1^1.2 zmol (10 221 mol) cDNA/PCR) followed by GD tissues (n ¼ 16, 9.6^3.5). Only low amounts were determined in thyroid autonomy (TA) (n ¼ 11) thyroid tissues, irrespective of whether the autonomous nodule (0.5^0.1) or the surrounding normal tissue (1.8^0.7) had been analyzed. The same differences were found for CXCR5 (HT: 179.1^6.8; GD: 17.4^10.6; TA nodule : 0.8^0.5; TA normal : 4.4^3.6). In GD, there is a correlation between CXCL13 and CXCR5 mRNA levels and the number of focal lymphocytic infiltrates and germinal centers as well as anti-thyroperoxidase but not anti-TSH receptor autoantibodies. Conclusions: CXCR5 and CXCL13 play an essential role in maintaining B-and T-cells in lymphocytic infiltrates and ectopic follicles in thyroid tissue from patients affected by autoimmunity. 150 225-234 European Journal of Endocrinology

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Section: Real-time Pcrmentioning

confidence: 99%

The role of CXCR5 and its ligand CXCL13 in the compartmentalization of lymphocytes in thyroids affected by autoimmune thyroid diseases

Aust

Sittig

Becherer

et al. 2004

European Journal of Endocrinology

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“…1,[8][9][10] The t(9;11) translocation, which is associated with the M5 subtype, predicts a favorable outcome. [10][11][12] In addition, many biologic and genetic features, which include internal tandem duplication of the FLT3 gene [13][14][15] and aberrant expression of drug-resistance transporter genes 16,17 and of BCL2 family genes, 18,19 are reportedly associated with outcome and are useful prognostic factors. Although many prognostic factors are now available, the accurate prediction of risk for treatment failure or relapse is still difficult.…”

Section: Introductionmentioning

confidence: 99%

Identification of a gene expression signature associated with pediatric AML prognosis

Yagi¹,

Morimoto

Eguchi

et al. 2003

Blood

171

125

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Most patients with acute myeloid leukemia (AML) enter complete remission (CR) after treatment with chemotherapy, but a large number of them experience relapse with resistant disease. To identify genes that are associated with their prognoses, we analyzed gene expression in 54 pediatric patients with AML using an oligonucleotide microarray that contained 12 566 probe sets. A supervised approach using the Student t test selected a prognostic set of 35 genes, some of which are associated with the regulation of cell cycle and apoptosis. Most of these genes had not previously been reported to be associated with prognosis and were not correlated with morphologically classified French-American-British (FAB) subtypes or with karyotypes. These results indicate the existence of prognosis-associated genes that are independent of cell lineage and cytogenetic abnormalities, and they can provide therapeutic direction for individual risk-adapted therapy for pediatric AML patients.

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“…Given that anti-and pro-apoptotic members interact with each other to suppress the activity of their partners (Bras et al, 2005;Oltvai et al, 1993;Willis and Adams, 2005), the ratios of protein or mRNA abundance between them are considered to be important factors in control of apoptosis (Cui and Kim, 2005;Hua et al, 2006;Kutlu et al, 2003;Köhler et al, 2002;Lynch et al, 2010;Mei et al, 2007;Takagi-Morishita et al, 2003;Viola-Rhenals et al, 2007;Xu et al, 2007). Actually, several studies had demonstrated that enhancement of the mRNA ratios of Bax, Bak and Bad to Bcl-xL were associated with the efficient induction of cellular apoptosis (Cui and Kim, 2005;Hua et al, 2006;Kutlu et al, 2003;Köhler et al, 2002;Takagi-Morishita et al, 2003;Xu et al, 2007). Similarly in the present study, EPO stimulation resulted in decreases in the mRNA ratios of Bax, Bak, and Bad to Bcl-xL, and concomitant reduction in apoptosis of late-stage erythroblasts.…”

Section: Discussionmentioning

confidence: 99%

“…Cell death is then induced through the activation of a cascade between caspase-9 and caspase-3 (Elmore, 2007). The balance of protein or mRNA abundance between the Bcl-2 family members is believed to regulate apoptosis and presumably determine the cell fate (Cui and Kim, 2005;Hua et al, 2006;Kutlu et al, 2003;Köhler et al, 2002;Lynch et al, 2010;Mei et al, 2007;Takagi-Morishita et al, 2003;Viola-Rhenals et al, 2007;Xu et al, 2007). In particular, it is known that Bcl-xL plays an important role as an antiapoptotic factor in erythropoiesis (Dolznig et al, 2002;Gregoli and Bondurant, 1997;Testa, 2004).…”

Section: Introductionmentioning

confidence: 99%

Bcl-xL and Mcl-1 are involved in prevention of in vitro apoptosis in rat late-stage erythroblasts derived from bone marrow

et al. 2012

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-Apoptosis controls erythroid homeostasis by balancing survival and death of erythroid cells. The mitochondrial pathway of apoptosis involves regulation of apoptotic events caused by the Bcl-2 family proteins, including the anti-apoptotic and pro-apoptotic members. However, little has been reported on the role of the anti-apoptotic Bcl-2 family members in rat late-stage erythroblasts that are no longer erythropoietin (EPO)-dependent. In the present study, to investigate this we analyzed changes in apoptosis-related factors that occurred in vitro. EPO stimulation resulted in reduced apoptotic cell death of the late-stage erythroblasts accompanied by decreased caspase-3 and caspase-9 activities, which is indicative of the induction of apoptosis through the mitochondrial pathway. Analysis of mRNA expression of the Bcl-2 family proteins demonstrated that EPO stimulation up-regulated the Bcl-xL mRNA, resulting in decreases in the mRNA ratios of Bak, Bax, and Bad to Bcl-xL. Also, the mRNA ratios of Bak and Noxa to Mcl-1 were decreased, mainly due to up-regulation of Mcl-1 mRNA. These results showed a close association between reduced apoptotic cell death and increased mRNA levels of Bcl-xL and Mcl-1 in the presence of EPO. Thus, the present study suggests that Bcl-xL may be an important anti-apoptotic factor of rat late-stage erythroblasts as has been reported in murine erythroblasts. Moreover, the results also indicate the possibility that Mcl-1 may act on the rat late-stage erythroblasts as an anti-apoptotic factor.

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High Bad and Bax mRNA expression correlate with negative outcome in acute myeloid leukemia (AML)

Cited by 66 publications

References 45 publications

The role of CXCR5 and its ligand CXCL13 in the compartmentalization of lymphocytes in thyroids affected by autoimmune thyroid diseases

The role of CXCR5 and its ligand CXCL13 in the compartmentalization of lymphocytes in thyroids affected by autoimmune thyroid diseases

Identification of a gene expression signature associated with pediatric AML prognosis

Bcl-xL and Mcl-1 are involved in prevention of in vitro apoptosis in rat late-stage erythroblasts derived from bone marrow

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