Ineffective haemopoiesis and apoptosis in myelodysplastic syndromes

Je, Parker; Mufti, G J

doi:10.1046/j.1365-2141.1998.00708.x

Cited by 79 publications

(61 citation statements)

References 98 publications

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“…[53][54][55][56][57][58] Increased Fas expression was detected on marrow CD34 cells from MDS patients. 42,55,56 Lack of correlation between Fas expression and apoptosis suggests that multiple mediators of cell death are operational. 55 Gupta and coinvestigators 59 have examined Fas ligand expression in marrows of MDS patients.…”

Section: Leukemiamentioning

confidence: 99%

“…A higher degree of apoptosis was seen in early FAB classes for both CD34 + cells or marrow aspirates in most studies. [53][54][55][56] Furthermore, as MDS clinically progresses, apoptotic signals decrease (Fas antigen, c-Myc oncoprotein) whereas anti-apoptotic signals increase (bcl-2 oncoprotein). 54,55,61 Fas-associated phosphatase-1 (fap-1) is a negative regulator of fas.…”

Section: Leukemiamentioning

confidence: 99%

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A hypothesis for the pathogenesis of myelodysplastic syndromes: implications for new therapies

2000

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Section: Leukemiamentioning

confidence: 99%

Section: Leukemiamentioning

confidence: 99%

A hypothesis for the pathogenesis of myelodysplastic syndromes: implications for new therapies

2000

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“…11 Myelodysplastic syndromes (MDS) are clonal disorders characterized initially by ineffective hematopoiesis and the frequent development of acute leukemia. [12][13][14] The underlying mechanisms of ineffective hematopoiesis in primary MDS have not yet been established, but may involve suppression by inhibitory cytokines, 15 enhanced spontaneous apoptosis, 12,16 and defective responses to growth factors due to aberrations of growth factor receptors 17 or post-receptor signal transduction pathways. 18 In addition, there is a block in cell differentiation of all three hematopoietic lineages.…”

Section: Introductionmentioning

confidence: 99%

Oral 9-cis retinoic acid (Alitretinoin) in the treatment of myelodysplastic syndromes: results from a pilot study

Hofmann

Kell

Fenaux³

et al. 2000

Leukemia

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A multicenter phase II study was initiated to investigate the efficacy, toxicity and tolerability of an oral regimen of 9-cis retinoic acid (9CRA) as a differentiation-inducing agent stimulating both retinoic acid receptor (RAR) and retinoic X receptor (RXR). Thirty patients with myelodysplastic syndromes (MDS) were enrolled into the study. The MDS subtypes were distributed as follows: 14 refractory anaemia (RA), four refractory anaemia with ringed sideroblasts (RARS), and 12 refractory anaemia with excess blasts (RAEB). The age ranged from 40 to 81 years (median 70). None of these had previously received treatment for MDS other than supportive therapy. 9CRA (Alitretinoin capsules, kindly provided by Allergan-Ligand Retinoid Therapeutics) was given daily at 60 mg/m 2 p.o. for 1 week, followed by an intra-patient escalation to 100 mg/m 2 during the second week, up to a maximum of 140 mg/m 2 . The planned treatment duration was 48 weeks. Twenty-five were available for assessment. One patient (4%) with RA achieved complete hematological remission. Four (16%), two with RA, two with RAEB, had minor responses resulting in decreased transfusion requirements or increased neutrophils. Thus, the overall response rate was 20% in evaluable patients with MDS and 17% in the study group on an intention-to-treat basis. The most frequent side-effects included headache (77%), dry skin (57%), arthralgias (30%), and rash (23%). In conclusion, although modest responses were noted in this study, the treatment tolerability was suboptimal. It is conceivable that a lower dosage schedule may be efficacious and better tolerated so enabling prolonged exposure which may be required to induce a differentiation effect. Leukemia (2000) 14, 1583-1588.

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“…15 Cytopenia in MDS is considered to be the result of pronounced hematopoietic insufficiency, and this ineffective hematopoiesis is contributed to the increased apoptosis of bone marrow precursors. 16 Several investigators have reported a higher incidence of F cells in patients with MDS compared with controls.…”

Section: Introductionmentioning

confidence: 99%

Significance of fetal hemoglobin-containing erythroblasts (F blasts) and the F blast/F cell ratio in myelodysplastic syndromes

et al. 2002

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To investigate the relationship between the fetal hemoglobincontaining erythroblasts (F blasts) and apoptosis in myelodysplastic syndromes (MDS), we immunohistochemically assessed F blasts, F cells, and apoptosis in 137 patients with MDS. A marked increase in the number of F blasts in the bone marrow was identified in 116 of 137 patients (84.7%), and the number of F cells was elevated in 54 patients (39.4%). Among the erythroblasts stained by anti-glycophorin C antibody, the mean percentage of F blasts was 14.63 ؎ 9.17% in MDS, which was significantly higher than that in non-MDS patients with stress erythropoiesis (4.82 ؎ 3.35%, P Ͻ 0.01), although there were no significant differences in the number of F cells between these groups. In particular, 62 of the 137 MDS patients (45.3%) had an apparent increase in F blasts but no elevation of F cells. The apoptotic rate was significantly higher in the patients with a F blast/F cell (Fb/Fc) ratio у5.0 than in those with a Fb/Fc ratio Ͻ1.0 (P Ͻ 0.01). The results indicate that F cell precursors are incapable of maturing into functioning endstage F cells, presumably owing to apoptotic cell death. The measurement of F blasts in the bone marrow is needed for the precise evaluation of fetal-type erythropoiesis in MDS.

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Ineffective haemopoiesis and apoptosis in myelodysplastic syndromes

Cited by 79 publications

References 98 publications

A hypothesis for the pathogenesis of myelodysplastic syndromes: implications for new therapies

A hypothesis for the pathogenesis of myelodysplastic syndromes: implications for new therapies

Oral 9-cis retinoic acid (Alitretinoin) in the treatment of myelodysplastic syndromes: results from a pilot study

Significance of fetal hemoglobin-containing erythroblasts (F blasts) and the F blast/F cell ratio in myelodysplastic syndromes

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