Differentiation Therapy of Myelodysplastic Syndromes: Fact or Fiction?

Santini, Valeria; Ferrini, Pierluigi Rossi

doi:10.1046/j.1365-2141.1998.00881.x

Cited by 24 publications

(12 citation statements)

References 117 publications

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“…71 Therapeutic trials of differentiating agents have not demonstrated consistent efficacy in ameliorating cytopenia. [72][73][74] Interpretation of the results from investigations of colonystimulating factor levels in MDS patients is difficult to discern. Results appear inconsistent (Table 1) and CSF levels may be altered by clinical events (ie infections).…”

Section: Leukemiamentioning

confidence: 99%

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

2000

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Section: Leukemiamentioning

confidence: 99%

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

2000

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“…MDS bone marrow (BM) progenitors can be induced to differentiate and mature in vitro by using various differentiating agents, such as vitamin D 3 and E, Ara-C, butyrates and amifostine and this has provided the rationale for several clinical trials [22].…”

Section: Introductionmentioning

confidence: 99%

Efficacy of N-acetylcysteine and all-trans retinoic acid in restoring in vitro effective hemopoiesis in myelodysplastic syndromes

et al. 2000

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We evaluated the in vitro effect on clonogenic potential (CFU-GM) and apoptosis in myelodysplastic syndromes (MDS) progenitors of an anti-oxidant (N-acetylcysteine, NAC) and/or a differentiating (all-trans retinoic acid, ATRA) agent. NAC significantly reduced apoptosis, both NAC and ATRA induced an increase in CFU-GM, but NAC seemed to be particularly effective in the high risk (HR) MDS. NAC + ATRA conferred a significant advantage in terms of CFU-GM with respect to NAC and ATRA alone. Tumor Necrosis Factor-a (TNF-a) levels decreased after incubation with NAC in the MDS samples. This study shows that ineffective hemopoiesis in MDS could benefit from both NAC and ATRA, suggesting that anti-oxidant treatment may play a role in guaranteeing MDS cell survival, predisposing them towards differentiation.

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“…MDS has also been the target of attempts at utilizing differentiation therapy with the use of agents such as interferon, polar planar compounds, homoharringtonine, 5-azacitidine, ara-c, butyrates, amifostine, retinoids, vitamin D derivatives, growth factors, and/or combinations of the above drugs [204]. Each of these agents has shown glimpses of differentiating activity, including single agent interferon [205][206][207][208][209], demethylating agents [170,171,173,174], vitamin D derivatives [210][211][212], and retinoids in combination with other compounds [179,213,214].…”

Section: Differentiation Therapy -Combinations That Improve Responsesmentioning

confidence: 99%

Myelodysplastic Syndromes: Review of Pathophysiology and Current Novel Treatment Approaches

Warlick¹,

Smith²

2007

CCDT

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Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal disorders of hematopoietic progenitors manifest by cytopenias, bleeding, infection, and potential for progression to acute myelogenous leukemia. The wide spectrum of clinical manifestations, including variability in illness severity and potential for progression, suggest that myelodysplastic syndromes encompass a multitude of disorders, likely involving numerous pathologic pathways. In fact, it is the effort to understand the underlying biology of these syndromes that has led to recent advances in treatment approaches, including the FDA approval of three new agents (5-azacitidine, decitabine, and lenalidomide) for the treatment of MDS. This review will present data supporting each of the current pathophysiologic pathways implicated in the development and progression of MDS; summarize the emerging clinical paradigms for treating patients with MDS; and offer insights into several novel approaches attempting to improve treatment options for future MDS patients.

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Differentiation Therapy of Myelodysplastic Syndromes: Fact or Fiction?

Cited by 24 publications

References 117 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

Efficacy of N-acetylcysteine and all-trans retinoic acid in restoring in vitro effective hemopoiesis in myelodysplastic syndromes

Myelodysplastic Syndromes: Review of Pathophysiology and Current Novel Treatment Approaches

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