Agranular CD4+/CD56+ Cutaneous Neoplasm

Touahri, Tahar; Belaouni, Hamid; Mossafa, Hossain; Pulik, M; Bourguignat, L.; Ibbora, C.; Soglio, Dorothée Dal; Davi, Frédéric; Fourcade, C.

doi:10.1080/1042819022386617

Cited by 9 publications

(2 citation statements)

References 16 publications

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“…In addition, 5 other studies reported a low CD33 expression in a least one case in their series of CD4 ϩ CD56 ϩ lineage-negative malignancies. 45,[47][48][49][50] Up-regulation of CD33 expression on leukemic pDCs in culture after maturation into potent APCs 17 also supports the idea that CD33 is expressed by pDCs during their differentiation process.One has also to consider the plasticity of DC differentiation. Canque and Gluckman 4 and Gluckman et al 51 have proposed that DCs may differentiate from many precursors (either immature or already committed to lymphoid or myeloid lineages).…”

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confidence: 59%

Expression of the myeloid-associated marker CD33 is not an exclusive factor for leukemic plasmacytoid dendritic cells

Garnache‐Ottou¹

2004

Blood

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A new entity of acute leukemia coexpressing CD4 ؉ CD56 ؉ markers without any other lineage-specific markers has been identified recently as arising from lymphoidrelated plasmacytoid dendritic cells (pDCs). In our laboratory, cells from a patient with such CD4 ؉ CD56 ؉ lineagenegative leukemia were unexpectedly found to also express the myeloid marker CD33. To confirm the diagnosis of pDC leukemia despite the CD33 expression, we demonstrated that the leukemic cells indeed exhibited pDC phenotypic and functional properties. In 7 of 8 other patients with CD4 ؉ CD56 ؉ pDC malignancies, we were able to confirm that the tumor cells expressed CD33 although with variable expression levels. CD33 expression was shown by flow cytometry, reverse transcriptase-polymerase chain reaction, and immunoblot analysis. Furthermore, CD33 monoclonal antibody stimulation of purified CD4 ؉ CD56 ؉ leukemic cells led to cytokine secretion, thus confirming the presence of a functional CD33 on these leukemic cells. Moreover, we found that circulating pDCs in healthy individuals also weakly express CD33. Overall, our results demonstrate that the expression of CD33 on CD4 ؉ CD56 ؉ lineage-negative cells should not exclude the diagnosis of pDC leukemia and underline that pDC-specific markers should be used at diagnosis for CD4 ؉ CD56 ؉ malignancies. IntroductionDendritic cells (DCs) are a heterogeneous population of bone marrow-derived cells. 1,2 Their ontogenic origin is still a matter of debate. 3,4 Recent identification of specific markers such as BDCA-2 and BDCA-4 5 and differential expression of CD11c 6 or CD16 7,8 suggest that at least 3 different types of DCs exist-one of lymphoid origin and 2 of myeloid origin. 1,2 Plasmacytoid DCs (pDCs), for which a lymphoid origin has been proposed, 3,9,10 express CD4, HLA-DR, CD123 high , BDCA-2, and BDCA-4, but they lack the conventional myeloid markers (myeloperoxidase [MPO], CD13, CD33, CD117). 2,5,[9][10][11][12] The pDC precursors probably correspond to peripheral blood natural type I interferon (IFN)-producing cells (IPCs) because they secrete high amounts of IFN-␣ on microbial infection. 25,26 pDCs have the potential to differentiate into mature DCs when they are cultured with interleukin 3 (IL-3) and CD40L or with viruses. 20,[27][28][29] This maturation is characterized by an increased expression of major histocompatibility complex (MHC) and costimulatory molecules (CD40, CD80, CD86) leading to potent T-cell activation. 9,[13][14][15] These pDCs may rather elicit a type 2 response after CD40L/IL-3 stimulation. 16 However, pDCs activated by influenza virus or cytosine-phosphate-guanine (CpG) motifs induce a potent type-1 response. 14 We recently described the identification of a leukemic counterpart of the pDC. 17 These leukemic cells, previously known as CD4 ϩ CD56 ϩ malignancies with the absence of conventional lineage markers, express CD123, 17 HLA-DR, 17 BDCA-2, and BDCA-4 18 ; produce IFN-␣ in response to inactivated influenza virus; and differentiate into potent mature antigen-presen...

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confidence: 59%

Expression of the myeloid-associated marker CD33 is not an exclusive factor for leukemic plasmacytoid dendritic cells

Garnache‐Ottou¹

2004

Blood

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“…The major difficulty with pDC and pDCL is that they may express shared markers with other lineages (Jacob et al, 2003), notably 'strong' markers used to calculate score (such as the EGIL score). CD33 was the most frequently reported myeloid marker (Gattei et al, 1990;Ginarte et al, 2000;Mhawech et al, 2000;Rakozy et al, 2001;Touahri et al, 2002;Karube et al, 2003;Kazakov et al, 2003;Bueno et al, 2004;Giagounidis et al, 2004;Garnache-Ottou et al, 2005a). We recently used functional assays to validate that both pDCL and normal pDC express CD33 at low levels (Garnache-Ottou et al, 2005a).…”

Section: Markers Expressed By Cells Of Plasmacytoid Dendritic Cell Lementioning

confidence: 99%

Plasmacytoid dendritic cell leukaemia/lymphoma: towards a well defined entity?

Garnache‐Ottou

Feuillard

Saas³

2007

Br J Haematol

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Summary CD4+/CD56+ haematodermic neoplasm or ‘early’ plasmacytoid dendritic cell leukaemia/lymphoma (pDCL) was described as a disease entity in the last World Health Organisation/European Organisation for Research and Treatment of Cancer classification for cutaneous lymphomas. These leukaemia/lymphomas co‐express CD4 and CD56 without any other lineage‐specific markers and have been identified as arising from plasmacytoid dendritic cells. Despite a fairly homogeneous pattern of markers expressed by most pDCL, numerous distinctive features (e.g. cytological aspects and aberrant marker expression) have been reported. This may be related to the ‘lineage‐independent developmental’ programme of dendritic cells, which may be able to develop from either immature or already committed haematopoietic progenitors. This highlights the need for specific validated markers to diagnose such aggressive leukaemia. Here, we propose –among others (e.g. T‐cell leukaemia 1) – blood dendritic cell antigen‐2 and high levels of CD123 expression as potential markers. In addition, we propose a multidisciplinary approach including several fields of haematology to improve pDCL diagnosis.

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Early plasmacytoid dendritic cell leukemia/lymphoma coexpressing myeloid antigenes

et al. 2004

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Early plasmacytoid dendritic cell (pDC) leukemia/lymphoma has recently been described as a CD4(+)CD56(+) lineage negative malignancy with characteristic clinical, morphologic, immunophenotypic, and biological features. We present a case of a 72-year-old man who was diagnosed with isolated skin involvement 30 months ago and received numerous chemotherapy cycles that did not prevent three relapses of the disease, the last two involving the bone marrow. The bone marrow was nearly completely infiltrated with small- to medium-sized blasts displaying a high nuclear to cytoplasmic ratio, a cytoplasm with faint basophilia lacking granulations or Auer rods. Small vacuoles surrounding the nucleus were frequently observed. Flow cytometry showed CD4(+), CD56(+), CD45(+), CD38(+), HLA-DR(+), CD33(+), CD123(+), CD2(-), cyCD3(-), CD7(-), CD10(-), CD11b(-), CD13(-), CD14(-), CD16(-), CD19(-), cyCD22(-), CD24(-), CD34(-), CD57(-), CD61(-), CD64(-), CD65(-), cyCD79a(-), CD117(-), MPO(-), and TdT(-) population. At the second bone marrow relapse, CD117 was also positive. Our patient was initially treated with acute myeloid leukemia-type chemotherapy, later he was given acute lymphoblastic leukemia-type treatment, and at the last relapse he received CHOP chemotherapy. Each treatment led to rapid response of tumor manifestations with disease-free intervals of 7 months, 9 months, and 8 months, respectively. Although patients usually have an ominous prognosis, with only 25% living more than 24 months, our patient is alive after 30+ months and has again achieved complete remission after the last chemotherapy.

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Agranular CD4+/CD56+ Cutaneous Neoplasm

Cited by 9 publications

References 16 publications

Expression of the myeloid-associated marker CD33 is not an exclusive factor for leukemic plasmacytoid dendritic cells

Expression of the myeloid-associated marker CD33 is not an exclusive factor for leukemic plasmacytoid dendritic cells

Plasmacytoid dendritic cell leukaemia/lymphoma: towards a well defined entity?

Early plasmacytoid dendritic cell leukemia/lymphoma coexpressing myeloid antigenes

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