Clinicobiological, immunophenotypic, and molecular characteristics of monoclonal CD56(-/+ dim) chronic natural killer cell large granular lymphocytosis

• Type: Article in International Scientific Journal
• Date: 2004

Authors

Montero, AG (Author) Other; Teixeira, MDA (Author) Other; Queiros, ML (Author) Other; Santos, AH (Author) Other; Balanzategui, A (Author) Other; Estevinho, A (Author) Other; Alguero, MDC (Author) Other; Barcena, P (Author) Other; Fonseca, S (Author) Other; Amorim, ML (Author) Other; Cabeda, JM (Author) Other; Pinho, L (Author) Other; Gonzalez, M (Author) Other; Miguel, JS (Author) Other; Justica, B (Author) Other; Orfao, A (Author) Other; Lima, M (Author) Other; Almeida, J (Author) Other

Journal

Title: American Journal of Pathology

Vol. 165

Pages: 1117-1127

ISSN: 0002-9440

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 35 Citations

Scopus - 32 Citations

Other information

Authenticus ID: P-000-85A

DOI: 10.1016/s0002-9440(10)63373-1

Abstract (EN): Indolent natural killer (NK) cell lymphoproliferative disorders include a heterogeneous group of patients in whom persistent expansions of mature, typically CD56(+), NK cells in the absence of any clonal marker are present in the peripheral blood. in the present study we report on the clinical, hematological, immunophenotypic, serological, and molecular features of a series of 26 patients with chronic large granular NK cell lymphocytosis, whose NK cells were either CD56(-) or expressed very low levels of CD56 (CD56(-/+dim) NK cells), in the context of an aberrant activation-related mature phenotype and proved to be monoclonal using the human androgen receptor gene polymerase chain reaction-based assay. As normal CD56+ NK cells, CD56(-/+dim) NK cells were granzyme B+, CD3(-), TCRalphabeta/gammadelta(-), CD5(-), CD28(-), CD11a(+bright), CD45RA(+bright), CD122(+), and CD25(-) and they showed variable and heterogeneous expression of both CD8 and CD57. Nevertheless, they displayed several unusual immunophenotypic features. Accordingly, besides being CD56 they were CD11b(-/+dim) (heterogeneous), CD7(-/+dim) (heterogeneous), CD2(+) (homogeneous), CD11c(+bright) (homogeneous), and CD38(-/+dim) (heterogeneous). Moreover, CD56(-/+dim) NK cells heterogeneously expressed HLA-DR. In that concerning the expression of killer receptors, CD56(-/+dim) NK cells showed bright and homogeneous CD94 expression, and dim and heterogeneous reactivity for CD161, whereas CD158a and NKB1 expression was variable. From the functional point of view, CD56(-/+dim) showed a typical Th1 pattern of cytokine production (interferon-gamma(+), tumor necrosis factor-alpha(+)). From the clinical point of view, these patients usually had an indolent clinical course, progression into a massive lymphocytosis with lung infiltration leading to death being observed in only one case. Despite this, they frequently had associated cytopenias as well as neoplastic diseases and/or viral infections. in summary, we describe a unique and homogeneous group of monoclonal chronic large granular NK cell lymphocytosis with an aberrant activation-related CD56(-/+dim)/CD11b(-/+dim) phenotype and an indolent clinical course, whose main clinical features are related to concomitant diseases.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11