The pathogenesis of myelodysplastic syndromes (MDS)

Platzbecker, Uwe; Meredyth-Stewart, Michelle; Ehninger, Gerhard

doi:10.1016/j.ctrv.2007.07.021

Cited by 10 publications

(11 citation statements)

References 73 publications

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“…It had been reported that in early MDS increased apoptosis is partially due to up regulation of TNF-α and death receptors [36]. Here we show that the levels of TNF-α and its downstream effector cleaved caspase 8 are markedly increased on day 14.…”

Section: Resultssupporting

confidence: 57%

“…Many blue siderotic granules were surrounding the nucleus, as evidence of dyserythropoiesis found in MDS guinea pigs [33] . It has been reported that pathologic iron accumulation occurs in the erythroblasts as evidence of dyserythropoiesis in MDS [35] , [36] . Figure 2AXIV depicts blue spots (Perls' stain) in the bone marrow of MDS guinea pigs that represent iron accumulation as evidence of dyserythropoiesis.…”

Section: Resultsmentioning

confidence: 99%

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NAD(P)H: Quinone Oxidoreductase 1 Deficiency Conjoint with Marginal Vitamin C Deficiency Causes Cigarette Smoke Induced Myelodysplastic Syndromes

et al. 2011

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BackgroundThe etiology of myelodysplastic syndromes (MDS) is largely unknown. Exposure to cigarette smoke (CS) is reported to be associated with MDS risk. There is inconsistent evidence that deficiency of NAD(P)H-quinone: oxidoreductase 1 (NQO1) increases the risk of MDS. Earlier we had shown that CS induces toxicity only in marginal vitamin C-deficient guinea pigs but not in vitamin C-sufficient ones. We therefore considered that NQO1 deficiency along with marginal vitamin C deficiency might produce MDS in CS-exposed guinea pigs.Methodology and Principal FindingsHere we show that CS exposure for 21 days produces MDS in guinea pigs having deficiency of NQO1 (fed 3 mg dicoumarol/day) conjoint with marginal vitamin C deficiency (fed 0.5 mg vitamin C/day). As evidenced by morphology, histology and cytogenetics, MDS produced in the guinea pigs falls in the category of refractory cytopenia with unilineage dysplasia (RCUD): refractory anemia; refractory thrombocytopenia that is associated with ring sideroblasts, micromegakaryocytes, myeloid hyperplasia and aneuploidy. MDS is accompanied by increased CD34(+) cells and oxidative stress as shown by the formation of protein carbonyls and 8-oxodeoxyguanosine. Apoptosis precedes MDS but disappears later with marked decrease in the p53 protein. MDS produced in the guinea pigs are irreversible. MDS and all the aforesaid pathophysiological events do not occur in vitamin C-sufficient guinea pigs. However, after the onset of MDS vitamin C becomes ineffective.Conclusions and SignificanceCS exposure causes MDS in guinea pigs having deficiency of NQO1 conjoint with marginal vitamin C deficiency. The syndromes are not produced in singular deficiency of NQO1 or marginal vitamin C deficiency. Our results suggest that human smokers having NQO1 deficiency combined with marginal vitamin C deficiency are likely to be at high risk for developing MDS and that intake of a moderately large dose of vitamin C would prevent MDS.

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Section: Resultssupporting

confidence: 57%

Section: Resultsmentioning

confidence: 99%

NAD(P)H: Quinone Oxidoreductase 1 Deficiency Conjoint with Marginal Vitamin C Deficiency Causes Cigarette Smoke Induced Myelodysplastic Syndromes

et al. 2011

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“…The precise characteristics of MDS stem cells, however, have not been fully defined, and uncertainty exists over whether MDS stem-cell clones might occasionally transgress the myeloid spectrum and give rise to cells with lymphoid or bone-marrow stromal characteristics. [8][9][10] laboratory studies that have demonstrated increased apoptosis of B cells and reports of clonal lympho cytes in a subset of patients with MDS suggest that lymphoid cells might occasionally be involved in, or affected during, the pathogenesis of the disorder. 11,12 Several points are important with respect to an evaluation of the concomitant occurrence of MDS and Ivl.…”

Section: Discussion Of Diagnosismentioning

confidence: 96%

Intravascular lymphomatosis of the brain in a patient with myelodysplastic syndrome

et al. 2009

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“…These are common hematological diseases in the elderly but are rarely observed in children [25]. The etiology and molecular pathogenesis of MDS are still poorly understood [26]. Both gene mutations and cytogenetic changes play important roles in the pathogenesis of this disease.…”

Section: Discussionmentioning

confidence: 99%

Myelodysplastic syndrome (MDS) associated with EBV infection in a pediatric patient

Manor

Shemer‐Avni²,

Boriakovski³

et al. 2013

OJPed

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Background: Epstein Barr Virus (EBV) is associated with different kinds of tumors. In the present study we tried to understand its role in pediatric MDS of a 4-year-old girl with EBV infection and MDS with refractory anemia and monosomy 7. Procedures: The work-up included: hematological tests; serology for IgM, IgG antibodies to EBV; PCR for EBV; cytogenetics of bone marrow (BM), and FISH analysis of BM and blood; immunohistochemistry-LMP1 expression on BM smears. Results: Hematological follow up showed constant mild dysplastic changes mostly in the erythroid lineage. PCR for EBV showed positive results in the nasopharygeal smears as well as in blood 15 weeks after disease onset. Cytogenetic analysis showed monosomy 7 in all the mitoses of BM sample. Fluorescence in situ hybridization (FISH) showed monosomy 7% in 57% of the cells, followed by a decreased tendency in the percentage of monosomy 7 cells in both BM and blood. Immunohistochemistry for EBV-latent membrane protein 1 (LMP-1) on the patient's BM smears, 21 weeks post disease onset, showed 9% positive cells, 80% of them carried monosomy 7. Conclusion: The parallel occurrence of the EBV infection and MDS, as well as the continuous EBV PCR positive and monosomy 7, support the possibility that they are related.

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The pathogenesis of myelodysplastic syndromes (MDS)

Cited by 10 publications

References 73 publications

NAD(P)H: Quinone Oxidoreductase 1 Deficiency Conjoint with Marginal Vitamin C Deficiency Causes Cigarette Smoke Induced Myelodysplastic Syndromes

NAD(P)H: Quinone Oxidoreductase 1 Deficiency Conjoint with Marginal Vitamin C Deficiency Causes Cigarette Smoke Induced Myelodysplastic Syndromes

Intravascular lymphomatosis of the brain in a patient with myelodysplastic syndrome

Myelodysplastic syndrome (MDS) associated with EBV infection in a pediatric patient

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