Oligoclonal T cell expansion in myelodysplastic syndrome: evidence for an autoimmune process

Epperson, Diane E.; Nakamura, Ryotaro; Saunthararajah, Yogen; Melenhorst, J. Joseph; Barrett, A. John

doi:10.1016/s0145-2126(01)00083-2

Cited by 109 publications

(90 citation statements)

References 19 publications

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“…Variables previously linked to clinical response to immune suppression include bone marrow hypocellularity, presence of HLA-DR15 expression, younger age, lower platelet count, blast percentage and shorter duration of transfusion requirement, which are primarily features associated with favorable prognosis. 5,13,14,18,19,55,56 The presence of clonal T cells was not significantly associated with any of the clinical factors examined, although there was a slight positive trend with increasing IPSS risk category. Multivariable analyses were limited by small sample size, thus, our data do not preclude the possibility that multiple clinical factors combined may be more strongly associated with immunologic activation than any single factor.…”

Section: Discussionmentioning

confidence: 90%

Prevalence and clinical association of clonal T-cell expansions in Myelodysplastic Syndrome

et al. 2007

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Selected patients with Myelodysplastic Syndromes (MDS) are responsive to immunosuppressive therapy, suggesting that hematopoietic suppressive T cells have a pathogenic role in ineffective hematopoiesis. We assessed T-cell receptor (TCR) clonality through combined flow cytometry and molecular analysis of the complementarity determining region (CDR)-3 of the T-cell receptor-Vb gene. We identified clonal T cells in 50% of MDS patients (n ¼ 52) compared to 5% of age-matched normal controls (n ¼ 20). The presence of T-cell clones was not associated with features linked previously to immunosuppression response, including WHO diagnostic category, karyotype, marrow cellularity, IPSS category, sex or age p60. Using flow cytometry to identify expanded Vb-families, we found that T cells showed greater expansion in the bone marrow compared with peripheral blood, and were characterized as CD8 þ /CD57 þ /CD28 À effector T cells. Expanded effector T cell were CD62L negative and expressed the natural killer C-lectinfamily receptor NKG2D and CD244 (2B4). We conclude that clonal T-cell expansion is common among all MDS prognostic subgroups.

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Section: Discussionmentioning

confidence: 90%

Prevalence and clinical association of clonal T-cell expansions in Myelodysplastic Syndrome

et al. 2007

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“…Consequently, activated T cells and clonal T-cell expansions are found in the majority of MDS patients. [3][4][5][6][7] However, the exact functional significance of these T cells remains unclear. 8 On the one hand, the immune response could be directed to the dysplastic pre-malignant precursor cells and represent immune-surveillance.…”

Section: Introductionmentioning

confidence: 99%

Immune mediated autologous cytotoxicity against hematopoietic precursor cells in patients with myelodysplastic syndrome

Chamuleau¹,

Westers²,

Dreunen³

et al. 2009

Haematologica

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“…Investigation revealed an abnormal T cell repertoire and T cell-mediated inhibition of bone marrow CFU-GM [131] as a potential mechanism to the response to ATG. Further characterization of the T cell repertoire in MDS patients demonstrated T cell expansion with recurrent patterns of V-Beta and J region skewing suggestive of unknown chronic antigenic stimulation [127] while other studies identified high percentages of cytotoxic T cells (CD8+, CD28-, CD57+) [132]. In aggregate, these findings indicate an activated immune environment [133].…”

Section: Immune System Dysregulationmentioning

confidence: 82%

“…Dysregulated immunity has been implicated in the development of all cancers, including MDS [127], but direct evidence in MDS has been difficult to uncover. The successful use of immunosuppressive therapies (i.e., cyclosporine-A, anti-thymocyte globulin), the potentially curative role of allogeneic stem cell transplant, and the more recent data showing improved peripheral cytopenias and elimination of certain common cytogenetic abnormalities with immunomodulatory agents (i.e., thalidomide and lenalidomide) highlight the role immune dysregulation plays in the development of MDS.…”

Section: Immune System Dysregulationmentioning

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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Oligoclonal T cell expansion in myelodysplastic syndrome: evidence for an autoimmune process

Cited by 109 publications

References 19 publications

Prevalence and clinical association of clonal T-cell expansions in Myelodysplastic Syndrome

Prevalence and clinical association of clonal T-cell expansions in Myelodysplastic Syndrome

Immune mediated autologous cytotoxicity against hematopoietic precursor cells in patients with myelodysplastic syndrome

Myelodysplastic Syndromes: Review of Pathophysiology and Current Novel Treatment Approaches

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