TCRγδ+ large granular lymphocyte leukemias reflect the spectrum of normal antigen-selected TCRγδ+ T-cells

Sandberg, Yorick; Almeida, Júlia; González, Marcos; Lima, Margarida; Bárcena, Paloma; Szczepański, Tomasz; Gastel-Mol, Ellen J. van; Wind, Henk; Balanzategui, Ana; Dongen, Jacques J. M. van; Miguel, Jesús F. San; Órfão, Alberto; Langerak, Anton W.

doi:10.1038/sj.leu.2404112

Cited by 84 publications

(117 citation statements)

References 51 publications

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“…In addition, these cases show a high degree of homology in the CDR3 region of the TCR-␤ chain, supporting the existence of a common chronic antigen-driven origin for this monoclonal CD4 ϩ T-LGL lymphoproliferative disorder. 2 However, in contrast to other T-LGL neoplasias (eg, TCR-␥␦ ϩ and CD8 ϩ TCR-␣␤ ϩ T-LGL), 3,4 CD4 ϩ T-LGL cases did not show a clear association with autoimmune disorders, pointing out the potential involvement of non-self-antigens in this lymphoproliferative disorder. 1,2 At present, it is well established that some viruses (eg, human T-cell lymphotropic virus type 1 (HTLV-1), Epstein-Barr virus (EBV), human herpesvirus 8 (HHV8), cytomegalovirus [CMV]) are capable of establishing long-term, persistent infections with chronic immune activation and inflammation.…”

Section: Introductionmentioning

confidence: 83%

Expanded cells in monoclonal TCR-αβ+/CD4+/NKa+/CD8−/+dim T-LGL lymphocytosis recognize hCMV antigens

Rodríguez-Caballero

García‐Montero

Bárcena

et al. 2008

Blood

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Section: Introductionmentioning

confidence: 83%

Expanded cells in monoclonal TCR-αβ+/CD4+/NKa+/CD8−/+dim T-LGL lymphocytosis recognize hCMV antigens

Rodríguez-Caballero

García‐Montero

Bárcena

et al. 2008

Blood

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“…22,23 Less than 10% of cases are TCR-␥␦ ϩ . 24,25 They do not differ from ␣␤ cases, except for a CD4 Ϫ / CD8 Ϫ phenotype similar to their normal counterparts. Fas (CD95) and Fas-Ligand (CD178) are expressed in the majority of cases.…”

Section: How We Diagnose Lgl Leukemiamentioning

confidence: 99%

How I treat LGL leukemia

Lamy

Loughran

2011

Blood

248

300

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“…26,27 Few cases are TCR gd 1 /CD4/CD8. 28,29 NK-LGL leukemia and NK-LGL lymphocytosis are characterized by the following phenotype: CD2 …”

Section: Epidemiologymentioning

confidence: 99%

LGL leukemia: from pathogenesis to treatment

Lamy

Moignet

Loughran

2017

Blood

244

391

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Large granular lymphocyte (LGL) leukemia has been recognized by the World Health Organization classifications amongst mature T-cell and natural killer (NK) cell neoplasms. There are 3 categories: chronic T-cell leukemia and NK-cell lymphocytosis, which are similarly indolent diseases characterized by cytopenias and autoimmune conditions as opposed to aggressive NK-cell LGL leukemia. Clonal LGL expansion arise from chronic antigenic stimulation, which promotes dysregulation of apoptosis, mainly due to constitutive activation of survival pathways including Jak/Stat, MapK, phosphatidylinositol 3-kinase–Akt, Ras–Raf-1, MEK1/extracellular signal-regulated kinase, sphingolipid, and nuclear factor-κB. Socs3 downregulation may also contribute to Stat3 activation. Interleukin 15 plays a key role in activation of leukemic LGL. Several somatic mutations including Stat3, Stat5b, and tumor necrosis factor alpha-induced protein 3 have been demonstrated recently in LGL leukemia. Because these mutations are present in less than half of the patients, they cannot completely explain LGL leukemogenesis. A better mechanistic understanding of leukemic LGL survival will allow future consideration of a more targeted therapeutic approach than the current practice of immunosuppressive therapy.

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TCRγδ+ large granular lymphocyte leukemias reflect the spectrum of normal antigen-selected TCRγδ+ T-cells

Cited by 84 publications

References 51 publications

Expanded cells in monoclonal TCR-αβ+/CD4+/NKa+/CD8−/+dim T-LGL lymphocytosis recognize hCMV antigens

Expanded cells in monoclonal TCR-αβ+/CD4+/NKa+/CD8−/+dim T-LGL lymphocytosis recognize hCMV antigens

How I treat LGL leukemia

LGL leukemia: from pathogenesis to treatment

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