Classification and Treatment of Rare and Aggressive Types of Peripheral T-Cell/Natural Killer-Cell Lymphomas of the Skin

Rezania, Dorna; Sokol, Lubomir; Cualing, Hernani

doi:10.1177/107327480701400204

Cited by 18 publications

(13 citation statements)

References 57 publications

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“…Together, these results indicate that constitutive JAK3 activation in this model mimics some important phenotypic features of a rare subset of human CD8 ϩ primary cutaneous peripheral T-cell lymphomas. [45][46][47] Finally, the results obtained in this murine model informed a screen that identified JAK3A572V as an infrequent allele in human CD4 ϩ CTCL. A larger cohort of patients will be required to determine its precise incidence in the different CTCL subsets, and whether other activating alleles in the JAK-STAT pathway contribute to human CTCL.…”

supporting

confidence: 62%

“…45,46 Infiltrated skin shows abnormal inflammation and presence of lymphoid clusters reminiscent of Pautrier microabcesses, intraepidermal collections of lymphocytes that are characteristic of epidermotropic human CTCLs. 46 Of further interest, the expanded JAK3-AV CD8 ϩ T cells demonstrate abnormal production of inflammatory or cytotoxic cytokines, including IFN␥ and TNF␣, that are likely to contribute to the development of skin lesions, mediated by massive infiltration of epidermotropic lymphocytes. Together, these results indicate that constitutive JAK3 activation in this model mimics some important phenotypic features of a rare subset of human CD8 ϩ primary cutaneous peripheral T-cell lymphomas.…”

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confidence: 99%

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Constitutive JAK3 activation induces lymphoproliferative syndromes in murine bone marrow transplantation models

Cornejo

Kharas

Werneck

et al. 2009

Blood

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The tyrosine kinase JAK3 plays a wellestablished role during normal lymphocyte development and is constitutively phosphorylated in several lymphoid malignancies. However, its contribution to lymphomagenesis remains elusive. In this study, we used the newly identified activating JAK3A572V mutation to elucidate the effect of constitutive JAK3 signaling on murine lymphopoiesis. In a bone marrow transplantation model, JAK3A572V induces an aggressive, fatal, and transplantable lymphoproliferative disorder characterized by the expansion of IntroductionLymphoid malignancies have been associated with mutations that result in altered function or overexpression in transcription factors, such as NOTCH1, LMO2, or TAL-1/SCL. [1][2][3] Myeloid malignancies are frequently associated with activating alleles of tyrosine kinases, including FLT3ITD or KITD816V in acute myeloid leukemia, 4 BCR-ABL1 in chronic myelogenous leukemia, 5 FIP1L1-PDGFRA in chronic eosinophilic leukemia, 6 TEL-PDGFRB in chronic myelomonocytic leukemia, 7 KITD816V in systemic mastocytosis, 8 and JAK2V617F in the most cases of primary myelofibrosis, polycythemia vera, and essential thrombocythemia. 9 In sharp contrast, only a few mutations in tyrosine kinases have been identified to date in lymphoid malignancies. Examples include fusions involving the anaplastic lymphoma kinase (ALK) gene and different partners, including the nucleophosmin (NPM) gene, which are found in a subset of anaplastic large cell lymphomas (ALCLs), 10 and the fusion between the nuclear pore protein NUP214 and the ABL1 kinase, which is present in approximately 5% of patients with T-cell acute lymphoblastic leukemia (T-ALL). 11 These examples and the frequent activation of downstream effectors of kinases in lymphoma [12][13][14] suggest that other mutations that activate kinases are likely to be found in lymphoid malignancies.The JAK3 tyrosine kinase plays a crucial and unique role in normal lymphocyte development and function. 15,16 JAK3 differs from the other members of the JAK family that include JAK1, JAK2, and TYK2, in several ways. Its expression is developmentally regulated and restricted to the hematopoietic compartment, 17 and it is the only member of the JAK family that interacts with the common gamma chain (␥ c ) of several interleukin receptors, including interleukin (IL)-2, IL-4, IL-7, IL-9, IL-15, and IL-21. Since these cytokine receptors are necessary for normal lymphopoiesis, loss of JAK3 or ␥ c function results in an early and severe block in T-cell and natural killer (NK) cell development and impaired B-cell function in mice and humans. 18 Collectively, diverse mutations in JAK3 account for approximately 7% to 14% of human severe combined immunodeficiency cases. 19 Conversely, JAK3 activation has been reported in several lymphoproliferative disorders, including mantle-cell lymphoma (MCL), 12 Burkitt lymphoma, 20 HTLV-1-induced adult T-cell lymphoma/leukemia (ATLL), 14 cutaneous T-cell lymphoma (CTCL), 21,22 and anaplastic large-cell lymphoma (ALCL). 23 Interestingly, ...

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supporting

confidence: 62%

mentioning

confidence: 99%

Constitutive JAK3 activation induces lymphoproliferative syndromes in murine bone marrow transplantation models

Cornejo

Kharas

Werneck

et al. 2009

Blood

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“…19,20 The prognosis of NHL also depends Mycosis fungoides/Sezary syndrome Adapted from Refs. [5][6][7][8][9] Tirumani et al on the disease subtype as well as other molecular factors. For example, the outcome in diffuse large B-cell lymphoma (DLBCL) is less favorable for patients with the activated B-cell-type DLBCL compared with the germinal center B-cell subtype on gene expression profiling and for those with a c-myc translocation either alone or with a BCL-2 translocation ("double hit").…”

Section: Staging and Prognosismentioning

confidence: 99%

“…5 NHL is further subdivided based on natural history into aggressive and indolent subtypes. [5][6][7][8][9] These subtypes are listed in Box 1.…”

Section: Clinical Background Lymphoma Classificationsmentioning

confidence: 99%

Role of 2-Deoxy-2-[18F]-fluoro-d-glucose-PET/Computed Tomography in Lymphoma

2015

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“…For prognostic and therapeutic reasons, this has to be differentiated from the similar other non-MF cutaneous T-cell lymphomas, identical-appearing secondary lymphomas, or even T-cell lymphomas masquerading as sarcoma (Alekshun et al Rezania et al 2007 ). Secondary lymphomas that involve the skin at presentation derived from systemic loci represent 25 % of all cutaneous lymphomas.…”

Section: Introductionmentioning

confidence: 99%

Cutaneous Hematopathology

2014

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Classification and Treatment of Rare and Aggressive Types of Peripheral T-Cell/Natural Killer-Cell Lymphomas of the Skin

Abstract: Background:The classification of cutaneous lymphomas has been contentious. Two

Cited by 18 publications

References 57 publications

Constitutive JAK3 activation induces lymphoproliferative syndromes in murine bone marrow transplantation models

Constitutive JAK3 activation induces lymphoproliferative syndromes in murine bone marrow transplantation models

Role of 2-Deoxy-2-[18F]-fluoro-d-glucose-PET/Computed Tomography in Lymphoma

Cutaneous Hematopathology

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