Phenotypic transformation of CD52pos to CD52neg leukemic T cells as a mechanism for resistance to CAMPATH-1H

Birhiray, Ruemu E.; Shaw, George H.; Guldan, S; Rudolf, Despina; Delmastro, Dean A.; Santabárbara, P.; Brettman, Lee R.

doi:10.1038/sj.leu.2402471

Cited by 18 publications

(8 citation statements)

References 22 publications

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“…Loss of CD20 or CD52 antigen expression following immunotherapy with rituximab or alemtuzumab is common. 12,30,31 It is interesting that none of our patients were treated with rituximab or alemtuzumab during the follow-up period, and thus, these antigenic changes are not due to binding by therapeutic antibody to the assessed antigen. However, modulation of the antigen or antigenic deletion in response to other therapeutic approaches cannot be ruled out.…”

Section: Discussionmentioning

confidence: 99%

Instability of Immunophenotype in Plasma Cell Myeloma

et al. 2008

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Section: Discussionmentioning

confidence: 99%

Instability of Immunophenotype in Plasma Cell Myeloma

et al. 2008

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“…The role of alemtuzumab in generating such a clonal expansion in our patient remains speculative, but, in agreement with this hypothesis, it has been shown that alemtuzumab cross-linking may result in T-cell activation in vitro 38,39 and that alemtuzumab may promote the expansion of CD52 Ϫ T-cell clones in vivo. [40][41][42] On the other hand, the expansion of nonmalignant T-cell clones may be unrelated to the disease or the treatment because expanded T-cell clones can be detected by molecular studies in the blood of patients, especially elderly patients, with benign dermatoses or non-CTCL malignant diseases. 27 Identifying one or several common antigen(s) specific to malignant Sézary cells, which may trigger or promote the proliferation of the malignant clone, would represent significant progress in the understanding of the pathogenesis of SS.…”

Section: Discussionmentioning

confidence: 99%

Significance of circulating T-cell clones in Sézary syndrome

Ortonne

Huet

Gaudez

et al. 2006

Blood

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Identification of malignant Sé zary cells by T-cell receptor (TCR) clonality studies is routinely used for the diagnosis of Sé zary syndrome, but T-cell clones expressed in a single patient have never been accurately characterized. We previously reported that CD158k expression delineates Sé zary syndrome malignant cells, and, more recently, we identified vimentin at the surface membranes of Sé zary cells and normal activated lymphocytes. In the present study, T-cell clones from 13 patients with Sé zary syndrome were identified by immunoscopy and further characterized in the blood according to their TCR V␤, CD158k, and vimentin cell-surface expression. We found in most patients a unique malignant T-cell clone that coexpressed CD158k and vimentin and that, when patients were tested, was also present in the skin. However, in some patients we detected the presence of a nonmalignant circulating clone expressing high amounts of vimentin and lacking IntroductionSézary syndrome (SS) is an erythrodermic, aggressive, cutaneous T-cell lymphoma characterized by a malignant T-cell clone that localizes in the blood and skin. In the absence of a specific marker for malignant Sézary cells, a diagnosis of SS relies on the circulating Sézary cell count and on the molecular detection of a circulating T-cell clone. Given that the cytomorphology of Sézary cells is not specific to SS, 1,2 identification of a specific marker of malignant Sézary cells has been a challenging issue. Besides a T-cell memory phenotype, CD4 ϩ CD45RO ϩ , Sézary cells were shown to lack CD26 3-5 and to have diminished CD3 expression, 6 whereas the loss of CD7 3,7 appears not to be a specific feature of the malignant T-cell clone. 5,8 More recently, it has been shown that Sézary cells specifically overexpress T-plastin, which, however, cannot be used as a cell-surface marker because it is located in the cytoskeleton, in association with actin. 9 New markers of Sézary cells were described, including KIR3DL2/CD158k, the first positive cell-surface marker of Sézary cells. In patients with SS, KIR3DL2/CD158k is dimly expressed by circulating and cutaneous CD4 ϩ lymphocytes. [10][11][12] In healthy persons, CD158k is absent in CD4 ϩ lymphocytes, and only minor subsets of T CD8 ϩ and natural killer (NK) lymphocytes express high amount of this antigen. 13 SC5 monoclonal antibody (mAb) was shown to react with an unknown cell-surface antigen expressed by normal activated lymphocytes and Sézary cells, whereas it failed to stain most circulating T lymphocytes in healthy individuals. 14 We found that SC5 mAb specifically recognizes vimentin (VIM) at the cell surface of viable activated T lymphocytes and is effectively expressed by Sézary cells. 15 The finding of an expanded T-cell clone in the blood of patients with SS is commonly considered to be a diagnostic marker. TCR V␤ phenotyping with specific mAbs may identify a "clonotypic" lymphocyte subset as an expanded population bearing a single TCR V␤ chain, which may be of diagnostic value. 3,[16][17][18] This approach, h...

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“…Evaluation of disease acceleration (e.g., CML blast crisis) or transformation (e.g., diffuse large B cell lymphoma in low grade lymphoma or CLL) (66, 74, 96, 171, 172). Prognostication, especially in CLL, with detection of ZAP70 or CD38 (135, 136, 173–179), acute leukemia (59, 77, 78, 180–185), or myeloma, whereby phenotype, presence of circulating plasma cells, or assessment of proliferation rate can predict progression (111, 114, 186–188). …”

Section: Clinical Signs and Symptomsmentioning

confidence: 99%

2006 Bethesda International Consensus recommendations on the flow cytometric immunophenotypic analysis of hematolymphoid neoplasia: Medical indications

Davis¹,

et al. 2007

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The clinical indications for diagnostic flow cytometry studies are an evolving consensus, as the knowledge of antigenic definition of hematolymphoid malignancies and the prognostic significance of antigen expression evolves. Additionally the standard of care is not routinely communicated to practicing clinicians and diagnostic services, especially as may relate to new technologies. Accordingly there is often uncertainty on the part of clinicians, payers of medical services, diagnostic physicians and scientists as to the appropriate use of diagnostic flow cytometry. In an attempt to communicate contemporary diagnostic utility of immunophenotypic flow cytometry in the diagnosis and follow-up of patients with hematolymphoid malignancies, the Clinical Cytometry Society organized a two day meeting of international experts in this area to reach a consensus as to this diagnostic tool. This report summarizes the appropriate use of diagnostic flow cytometry as determined by unanimous approval of these experienced practitioners. q 2007 Clinical Cytometry Society

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Phenotypic transformation of CD52pos to CD52neg leukemic T cells as a mechanism for resistance to CAMPATH-1H

Cited by 18 publications

References 22 publications

Instability of Immunophenotype in Plasma Cell Myeloma

Instability of Immunophenotype in Plasma Cell Myeloma

Significance of circulating T-cell clones in Sézary syndrome

2006 Bethesda International Consensus recommendations on the flow cytometric immunophenotypic analysis of hematolymphoid neoplasia: Medical indications

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