Mitochondria in hematopoiesis and hematological diseases

Fontenay, Michaëla; Cathelin, Séverine; Amiot, Martine; Gyan, Emmanuel; Solary, Éric

doi:10.1038/sj.onc.1209606

Cited by 78 publications

(58 citation statements)

References 166 publications

(154 reference statements)

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“…lymphoma predictor set) is normally specifically expressed in erythroid cells. Because defective ALAS2 has been linked to sideroblastic anemia and diminished heme production, ALAS2 function can enhance cellular survival, as excess iron promotes reactive oxygen species (38). Therefore, increased ALAS2 may function to decrease reactive oxygen species and promote mitochondrial stability.…”

Section: Discussionmentioning

confidence: 99%

Identification of Expression Signatures Predictive of Sensitivity to the Bcl-2 Family Member Inhibitor ABT-263 in Small Cell Lung Carcinoma and Leukemia/Lymphoma Cell Lines

Tahir

Wass

Joseph

et al. 2010

Molecular Cancer Therapeutics

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ABT-263 inhibits the antiapoptotic proteins Bcl-2, Bcl-x L , and Bcl-w and has single-agent efficacy in numerous small cell lung carcinoma (SCLC) and leukemia/lymphoma cell lines in vitro and in vivo. It is currently in clinical trials for treating patients with SCLC and various leukemia/lymphomas. Identification of predictive markers for response will benefit the clinical development of ABT-263. We identified the expression of Bcl-2 family genes that correlated best with sensitivity to ABT-263 in a panel of 36 SCLC and 31 leukemia/ lymphoma cell lines. In cells sensitive to ABT-

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Section: Discussionmentioning

confidence: 99%

Identification of Expression Signatures Predictive of Sensitivity to the Bcl-2 Family Member Inhibitor ABT-263 in Small Cell Lung Carcinoma and Leukemia/Lymphoma Cell Lines

Tahir

Wass

Joseph

et al. 2010

Molecular Cancer Therapeutics

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“…Qualitative aberrations of mtDNA, such as mutations, have been found in solid tumours, such as colon, stomach, liver, kidney, bladder, prostate, skin and lung cancer (Copeland et al 2002;Penta et al 2001), and in haematological malignancies, such as leukaemia and lymphoma (Fontenay et al 2006). Quantitative aberrations of mtDNA have been observed in various sample types from patients with cancers (Mambo et al 2005).…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial DNA content in paired normal and cancerous breast tissue samples from patients with breast cancer

Fan

Radpour

Haghighi

et al. 2009

J Cancer Res Clin Oncol

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Introduction We develop a multiplex quantitative realtime PCR for synchronized analysis of mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) to investigate relative mtDNA abundance in paired normal and cancerous breast tissues. Materials and methodsThe amounts of nDNA and mtDNA in 102 tissue samples were quantiWed for both glyceraldehype-3-phosphodehydrogenase (GAPDH) gene and mtDNA encoded ATPase (MTATP) 8 gene. The average threshold cycle (Ct) number values of the nDNA and mtDNA were used to calculate relative mtDNA content in breast tissues. Results The median delta Ct ( Ct) and the median mtDNA content for normal and cancerous breast tissues were 6.73 and 2.54, as well as 106.50 and 5.80 (P = 0.000, respectively). The mtDNA content was decreased in 82% of cancerous breast tissues compared with the normal ones. The changes were associated with hormone receptor status. Conclusion Our Wnding suggests that decreased mtDNA content in breast cancer may have diagnostic and prognostic value for the disease.

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“…6 The metabolic status of HSC and HPC becomes crucial during clinical HSPC transplantation since the efficiency of donor-derived HSC/HPC to engraft, survive, home, proliferate and differentiate into multiple lineages in a chemotherapy-induced aplastic patient is markedly influenced by their hypoxic niche, demanding a significant metabolic adaptation to survive and promote rapid and stable hematopoietic reconstitution in chemotherapyinduced aplastic microenvironments. 7,8 As in other tissues, mitochondria play key roles in HSC/HPC and have recently come under increased scrutiny because compelling evidence has revealed their role in numerous cellular processes, beyond ATP production and apoptosis regulation, and they have recently even been suggested to act as cell-fate or lineage determinants. [9][10][11] In fact, deregulation of mitochondrial function plays a pathophysio- October 11, 2012.…”

Section: Introductionmentioning

confidence: 99%

“…logical role in a range of hematologic diseases, such as inherited dyserythropoiesis, sideroblastic anemias and low-grade myelodysplastic symdromes. 8,12 In addition, transcriptome, epigenetic and proteomic studies in stem cell systems have indicated that specific metabolic/mitochondrial properties are essential for regulating the balance between self-renewal and differentiation. 13,14 Although recent work has begun to shed light on the mitochondrial response during murine stem cell differentiation, 7,10,15,16 how and to what extent the mitochondrial mass/function contributes to human hematopoietic stem and progenitor function remains poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Cord blood-derived CD34+ hematopoietic cells with low mitochondrial mass are enriched in hematopoietic repopulating stem cell function

et al. 2013

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ABSTRACT© F e r r a t a S t o r t i F o u n d a t i o n . logical role in a range of hematologic diseases, such as inherited dyserythropoiesis, sideroblastic anemias and low-grade myelodysplastic symdromes. 8,12 In addition, transcriptome, epigenetic and proteomic studies in stem cell systems have indicated that specific metabolic/mitochondrial properties are essential for regulating the balance between self-renewal and differentiation. 13,14 Although recent work has begun to shed light on the mitochondrial response during murine stem cell differentiation, 7,10,15,16 how and to what extent the mitochondrial mass/function contributes to human hematopoietic stem and progenitor function remains poorly understood. Here, we found that mitochondrial mass correlates strongly with mitochondrial membrane potential (ΔΨm Design and Methods Cord blood collection and CD34 + cell isolation and cultureFresh umbilical cord blood units from healthy neonates were obtained from local hospitals following approval from our local Ethics and Biohazard Board Committee. The cord blood samples were pooled to reduce variability among individual units. Mononuclear cells were isolated using Ficoll-Hypaque and after lysing the red cells (Cytognos, Salamanca, Spain), CD34 + cells were purified by magnetic bead separation using the human CD34 MicroBead kit and the AutoMACS Pro separator (Miltenyi Biotec) as instructed by the manufacturer. [17][18][19] The purity of the CD34 + fraction was assessed by flow cytometry using an anti-CD34-PE antibody (Miltenyi Biotec), and only CD34 + fractions showing purity higher than 90% were used. [17][18][19] The CD34 -fraction was irradiated (15 Gy) and used as accessory cells for co-transplantation with CD34 + cells. MitoTracker staining and cell sortingCD34 + cells were stained with MitoTracker Red (CMXRos) and MitoTracker Green FM dye (Molecular Probes) for 10 min and 20 min, respectively, according to the manufacturer's guidelines and analyzed by wide confocal cytometry. 6 For functional assays, CD34 + cells were FACS-sorted (FACSAria-II, BD Biosciences) based on MitoTracker Green levels into CD34 + Mito High and CD34 + Mito Low (n=10). Measurements of ATP and reactive oxygen speciesATP levels were measured using a Cell-Titer-Glo ® Luminescent Cell Viability Assay (Promega) according to the manufacturer's guidelines. Briefly, equal numbers of cells (5x10 4 /100 mL) were seeded in a 96-well plate and 100 mL of the reaction reagent were added to each well. After 10 min of shaking, the luminescence signal was detected using the GloMax ® -Multi Detection System (Promega) and compared against the ATP Standard Curve using ATP disodium salt (Promega). 6 Reactive oxygen species were measured using the mitochondrial superoxide indicator MitoSOX Red, as previously described. 20 Briefly, CD34 + Mito Low and CD34 + Mito High cells were treated with 3 mM MitoSOX for 20 min and were then washed twice in Hanks balanced salt solution and analyzed by flow cytometry (Online Supplementary Figure S1A). Gene expression by q...

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Mitochondria in hematopoiesis and hematological diseases

Cited by 78 publications

References 166 publications

Identification of Expression Signatures Predictive of Sensitivity to the Bcl-2 Family Member Inhibitor ABT-263 in Small Cell Lung Carcinoma and Leukemia/Lymphoma Cell Lines

Identification of Expression Signatures Predictive of Sensitivity to the Bcl-2 Family Member Inhibitor ABT-263 in Small Cell Lung Carcinoma and Leukemia/Lymphoma Cell Lines

Mitochondrial DNA content in paired normal and cancerous breast tissue samples from patients with breast cancer

Cord blood-derived CD34+ hematopoietic cells with low mitochondrial mass are enriched in hematopoietic repopulating stem cell function

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