Clinicobiological, immunophenotypic, and molecular characteristics of monoclonal CD56-/+dim chronic natural killer cell large granular lymphocytosis.
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(-/+dim), 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.
Serviço de Hematologia, Unidade de Citometria, Hospital Geral de Santo António, Rua D Manuel II, s/n, 4099-001 Porto, Portugal. mmc.lima@clix.pt.
Margarida
M
Lima
Julia
J
Almeida
Andrés García
AG
Montero
Maria dos Anjos
Mdos A
Teixeira
Maria Luís
ML
Queirós
Ana Helena
AH
Santos
Ana
A
Balanzategui
Alexandra
A
Estevinho
Maria del Cármen
Mdel C
Algueró
Paloma
P
Barcena
Sónia
S
Fonseca
Maria Luís
ML
Amorim
José Manuel
JM
Cabeda
Luciana
L
Pinho
Marcos
M
Gonzalez
Jesus
J
San Miguel
Benvindo
B
Justiça
Alberto
A
Orfão
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D015139:Blotting, Southern; D019002:CD56 Antigen / Q000378:metabolism*; D002908:Chronic Disease; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D005434:Flow Cytometry; D015329:Gene Rearrangement, T-Lymphocyte; D006402:Hematologic Diseases / Q000150:complications; D006801:Humans; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism*; D008218:Lymphocytosis / Q000150:complications / Q000235:genetics* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications; D016133:Polymerase Chain Reaction; D014777:Virus Diseases / Q000150:complications
D014408:Biomarkers, Tumor; D019002:CD56 Antigen; D016207:Cytokines