Recent advances in myelodysplastic syndromes

Shadduck, Richard K.; Latsko, Joan; Rossetti, James M.; Haq, Bushra; Abdulhaq, Haifaa

doi:10.1016/j.exphem.2007.01.022

Cited by 24 publications

(23 citation statements)

References 30 publications

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“…The majority of bibliographic data though support the idea that p21 may act as an apoptosis inhibitor, in contradiction to our results [44]. There are yet a number of reports that suggest a pro-apoptotic function of p21 under certain conditions in specific systems and are in agreement with our findings [47][48][49][50][51][52][53][54][55][56]. Further investigation of the role of p21 in apoptosis is required.…”

Section: Discussioncontrasting

confidence: 88%

Cell cycle and apoptosis regulatory gene expression in the bone marrow of patients with de novo myelodysplastic syndromes (MDS)

et al. 2009

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Section: Discussioncontrasting

confidence: 88%

Cell cycle and apoptosis regulatory gene expression in the bone marrow of patients with de novo myelodysplastic syndromes (MDS)

et al. 2009

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“…16,17 These trials showed that lenalidomide significantly reduced the transfusion requirements of patients with MDS with a normal karyotype or with del(5q). 13,18 Subsequent trials have shown that lenalidomide also has clinical activity in other patient groups with MDS, including low or intermediate-1 risk patients without del(5q) and intermediate-2 or high-risk patients with del(5q). 17,19,20 Lenalidomide's mode of action in MDS is not well understood, but its proposed biological effects include inhibition of angiogenesis, promotion of erythroid hemoglobin production and acceleration of apoptotic death of abnormal hematopoietic progenitors, 16,17,21 and it is also reported to have immunoregulatory activity through modulation of natural killer cell, monocyte and dendritic cell function, inhibition of FOXP3 þ T regulatory cells and costimulation of T cells leading to increased proliferation and interferon-g (IFN-g) production.…”

Section: Introductionmentioning

confidence: 99%

“…[10][11][12] MDS is a collective term for a heterogenous group of clonal stem cell disorders characterized by ineffective production of mature blood cells, blood cytopenias and a predisposition to acute myeloid leukemia. 13,14 Chromosomal abnormalities are detected in approximately 50% of de novo MDS cases and of these, interstitial deletions of chromosome 5q31.1 (del(5q)) are the most common. 15 Conventional therapeutic management of MDS has usually been restricted to supportive measures such as red blood cell or platelet transfusion and recombinant growth factors; however, recent clinical trials have showed that the thalidomide analogue lenalidomide (Revlimid; Celgene, Summit, NJ, USA) can induce substantial clinical improvements.…”

Section: Introductionmentioning

confidence: 99%

Testing the NKT cell hypothesis in lenalidomide-treated myelodysplastic syndrome patients

et al. 2010

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Myelodysplastic syndrome (MDS) comprises a group of clonal bone marrow disorders characterized by ineffective hematopoiesis and increased predisposition to acute myeloid leukemia. The causes of MDS remain poorly defined, but several studies have reported the NKT cell compartment of patients with MDS is deficient in number and functionally defective. In support of a central role for NKT cells, a pilot clinical study reported that lenalidomide (an approved treatment for MDS) increased NKT cell numbers in patients with MDS, and several in vitro studies showed lenalidomide specifically promoted NKT cell proliferation and cytokine production. We tested this in a much larger study and confirm a moderate in vitro augmentation of some NKT cell functions by lenalidomide, but find no impact on the NKT cell compartment of patients treated with lenalidomide, despite a consistently positive clinical response. We further show that the frequency and cytokine production of NKT cells is normal in patients with MDS before treatment and remains stable throughout 10 months of lenalidomide therapy. Collectively, our data challenge the concept that NKT cell defects contribute to the development of MDS, and show that a clinical response to lenalidomide is not dependent on modulation of NKT cell frequency or function.

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“…In the pathological conditions of myelodysplasia or leukemia, clonal blast cells become involved in abnormal differentiation pathways or arrested at a given stage of differentiation (1,2). For decades, morphological examination of BM smears has been the only means to discriminate between lineages and lineage-related maturation stages.…”

mentioning

confidence: 99%

Four‐ and five‐color flow cytometry analysis of leukocyte differentiation pathways in normal bone marrow: A reference document based on a systematic approach by the GTLLF and GEIL

Arnoulet

Béné

Durrieu

et al. 2009

Cytometry Part B Clinical

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Background: The development of multiparameter flow cytometry (FCM) and increasingly sophisticated analysis software has considerably improved the exploration of hematological disorders. These tools have been widely applied in leukaemias, lymphomas, and myelodysplasias, yet with very heterogeneous approaches. Consequently, there is no extensive reference document reporting on the characteristics of normal human bone marrow (BM) in multiparameter FCM. Here, we report a reference analysis procedure using relevant antibody combinations in normal human BM.Methods: A first panel of 23 antibodies, constructed after literature review, was tested in four-color combinations (including CD45 in each) on 30 samples of BM. After evaluation of the data, a second set of 22 antibodies was further applied to another 35 BM samples. All list-modes from the 65 bone marrow samples were reviewed collectively. A systematised protocol for data analysis was established including biparametric representations and color codes for the three major lineages and undifferentiated cells.Results: This strategy has allowed to obtain a reference atlas of relevant patterns of differentiation antigens expression in normal human BM that is available within the European LeukemiaNet. This manuscript describes how this atlas was constructed.Conclusions: Both the strategy and atlas could prove very useful as a reference of normality, for the determination of leukemia-associated immunophenotypic patterns, analysis of myelodysplasia and, ultimately, investigation of minimal residual disease in the BM. V C 2009 Clinical Cytometry Society

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Recent advances in myelodysplastic syndromes

Cited by 24 publications

References 30 publications

Cell cycle and apoptosis regulatory gene expression in the bone marrow of patients with de novo myelodysplastic syndromes (MDS)

Cell cycle and apoptosis regulatory gene expression in the bone marrow of patients with de novo myelodysplastic syndromes (MDS)

Testing the NKT cell hypothesis in lenalidomide-treated myelodysplastic syndrome patients

Four‐ and five‐color flow cytometry analysis of leukocyte differentiation pathways in normal bone marrow: A reference document based on a systematic approach by the GTLLF and GEIL

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