RESUMEN
In adult acute myeloid leukaemia (AML), immunophenotypic differences enable discrimination of leukaemic stem cells (LSCs) from healthy haematopoietic stem cells (HSCs). However, immunophenotypic stem cell characteristics are less explored in paediatric AML. Employing a 15-colour flow cytometry assay, we analysed the expression of eight aberrant surface markers together with BCL-2 on CD34+ CD38- bone marrow stem cells from 38 paediatric AML patients and seven non-leukaemic, age-matched controls. Furthermore, clonality was investigated by genetic analyses of sorted immunophenotypically abnormal stem cells from six patients. A total of 50 aberrant marker positive (non-HSC-like) subsets with 41 different immunophenotypic profiles were detected. CD123, CLEC12A, and IL1RAP were the most frequently expressed markers. IL1RAP, CD93, and CD25 expression were not restricted to stem cells harbouring leukaemia-associated mutations. Differential BCL-2 expression was found among defined cytogenetic subgroups. Interestingly, only immunophenotypically abnormal non-HSC-like subsets demonstrated BCL-2 overexpression. Collectively, we observed pronounced immunophenotypic heterogeneity within the stem cell compartment of paediatric AML patients. Additionally, certain aberrant markers used in adults seemed to be ineligible for detection of leukaemia-representing stem cells in paediatric patients implying that inference from adult studies must be done with caution.
Asunto(s)
Leucemia Mieloide Aguda , Células Madre Neoplásicas , Adulto , Antígenos CD34/metabolismo , Biomarcadores/metabolismo , Niño , Análisis Citogenético , Humanos , Inmunofenotipificación , Subunidad alfa del Receptor de Interleucina-3 , Lectinas Tipo C/metabolismo , Leucemia Mieloide Aguda/diagnóstico , Células Madre Neoplásicas/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Receptores Mitogénicos/genéticaRESUMEN
Aim: To estimate current real-world costs of drugs and supportive care for the treatment of multiple myeloma in a tax-based health system. Methods: Forty-one patients were included from a personalized medicine study (2016-2019). Detailed information was collected from patient journals and hospital registries to estimate the total and mean costs using inverse probability weighting of censored data. Results: Total observed (censored) costs for the 41 patients was 8.84 million during 125 treatment years, with antineoplastic drugs as the main cost driver (5.6 million). Individual costs showed large variations. Mean 3-year cost per patient from first progression was 182,103 (131,800-232,405). Conclusion: Prediction of real-world costs is hindered by the availability of detailed costing data. Micro-costing analyses are needed for budgeting and real-world evaluation of cost-effectiveness.
Lay abstract In recent years, there has been a dramatic improvement in the treatment of multiple myeloma due to the introduction of new drugs. These drugs have significantly increased survival but have also had an immense impact on healthcare budgets. In this study, we used detailed treatment information for multiple myeloma patients in combination with billing data from the hospital pharmacy at a Danish hospital to calculate individual cost histories for both drugs and supportive care. Using these data, we estimated the mean 3-year cost of a multiple myeloma patient to be 182.103, but we also found large variation between patients, causing an uncertainty of 50.000 in either direction. We believe that detailed costing studies, similar to the present one, are necessary for evaluation of cost-effectiveness of drugs in clinical practice.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/economía , Costo de Enfermedad , Costos de la Atención en Salud/estadística & datos numéricos , Mieloma Múltiple/economía , Cuidados Paliativos/economía , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Análisis Costo-Beneficio/estadística & datos numéricos , Dinamarca/epidemiología , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Oncología Médica/economía , Oncología Médica/normas , Oncología Médica/estadística & datos numéricos , Persona de Mediana Edad , Mieloma Múltiple/mortalidad , Mieloma Múltiple/terapia , Programas Nacionales de Salud/economía , Programas Nacionales de Salud/normas , Programas Nacionales de Salud/estadística & datos numéricos , Cuidados Paliativos/estadística & datos numéricos , Guías de Práctica Clínica como Asunto , Supervivencia sin Progresión , Sistema de Registros/estadística & datos numéricos , Factores de TiempoRESUMEN
With rising life expectancy, the importance of patient-related prognostic factors and how to integrate such data into clinical decision-making becomes increasingly important. The aim of this study was to evaluate the prognostic impact of smoking status in patients with acute myeloid leukaemia (AML) treated with intensive chemotherapy. We conducted a nationwide cohort study based on data obtained from the Danish National Leukaemia Registry (DNLR). The study comprised Danish patients aged 18-75 years, diagnosed with AML between 1 January 2000 and 31 December 2012. Medical records were reviewed and data on smoking status were collected. A total of 1040 patients (median age 59 years) were included, and 602 patients (58·9%) were categorised as ever-smokers and the remaining as never-smokers. Kaplan-Meier survival estimates revealed that ever-smokers had a significant shorter median overall survival (OS) at 17·2 months [95% CI (14·9;19·1)] compared to never-smokers at 24·5 months (95% CI [19·2;30·7]). Multivariate analysis revealed smoking status as a significant prognostic factor for inferior OS with a hazard ratio (HR) of 1·22 [95% CI (1·04;1·44)]. In conclusion, smoking status was found to be associated with inferior OS in intensively treated AML patients.
Asunto(s)
Leucemia Mieloide Aguda/complicaciones , Fumar/efectos adversos , Adolescente , Adulto , Anciano , Dinamarca , Femenino , Humanos , Leucemia Mieloide Aguda/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Análisis de Supervivencia , Resultado del Tratamiento , Adulto JovenRESUMEN
Targeted therapy directed against rare disease-propagating leukaemic stem cells (LSCs) is a promising prospect for improving the outcome of acute myeloid leukaemia (AML) patients. Thus, distinguishing LSCs from normal haematopoietic stem and progenitor cells (HSPCs) is essential. The CLEC12A receptor has been proposed as a specific marker of LSCs, and consequently as an appealing treatment target. To explore the role of CLEC12A in further detail, we investigated whether a sorting strategy based on the activity of aldehyde dehydrogenase and CLEC12A expression could separate residual normal HSPCs from LSCs in bone marrow from 5 AML patients. We demonstrate that this distinction was possible in 2/5 cases, however with evidence of pre-leukaemic mutations in the CLEC12A- stem cells in one case. In contrast, cytogenetic and/or molecular aberrations were detected in both the CLEC12A+/- cell subsets in 3/5 AML cases studied. Furthermore, targeted next generation sequencing (NGS) of the sorted cell subsets revealed a pronounced clonal heterogeneity in the CLEC12A- cells suggestive of the leukaemia often originating in this immature cell subset. In conclusion, we provide proof-of-concept that precision diagnostics employing targeted cytogenetic/NGS-based analyses on highly purified cell subsets could be a powerful tool for selecting patients eligible for LSC-directed therapy.
Asunto(s)
Biomarcadores de Tumor , Lectinas Tipo C , Leucemia Mieloide Aguda , Mutación , Proteínas de Neoplasias , Células Madre Neoplásicas/metabolismo , Receptores Mitogénicos , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Femenino , Células Madre Hematopoyéticas/metabolismo , Humanos , Lectinas Tipo C/genética , Lectinas Tipo C/metabolismo , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Masculino , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Receptores Mitogénicos/genética , Receptores Mitogénicos/metabolismoRESUMEN
We describe a comprehensive molecular analysis of a pair of monozygotic twins, who came to our attention when one experienced amaurosis fugax and was diagnosed with JAK2+ polycythaemia vera. He (Twin A) was also found to have an asymptomatic B-cell chronic lymphocytic leukaemia (B-CLL). Although JAK2-, Twin B was subsequently shown to have a benign monoclonal B-cell lymphocytosis (MBL). Flow cytometric and molecular analyses of the B-cell compartments revealed different immunoglobulin light and heavy chain usage in each twin. We hypothesized that whole exome sequencing could help delineating the pattern of germline B-cell disorder susceptibility and reveal somatic mutations potentially contributing to the differential patterns of pre-malignancy. Comparing bone marrow cells and T cells and employing in-house engineered integrative analysis, we found aberrations in Twin A consistent with a myeloid neoplasm, i.e. in TET2, RUNX1, PLCB1 and ELF4. Employing the method for detecting high-ranking variants by extensive annotation and relevance scoring, we also identified shared germline variants in genes of proteins interacting with B-cell receptor signalling mediators and the WNT-pathway, including IRF8, PTPRO, BCL9L, SIT1 and SIRPB1, all with possible implications in B-cell proliferation. Similar patterns of IGHV-gene usage to those demonstrated here have been observed in inherited acute lymphoblastic leukaemia. Collectively, these findings may help in facilitating identification of putative master gene(s) involved in B-cell proliferations in general and MBL and B-CLL in particular.
Asunto(s)
Leucemia Linfocítica Crónica de Células B/etiología , Leucemia Linfocítica Crónica de Células B/patología , Lesiones Precancerosas , Gemelos Monocigóticos , Anciano , Hibridación Genómica Comparativa , Exoma , Predisposición Genética a la Enfermedad , Mutación de Línea Germinal , Humanos , Cadenas Pesadas de Inmunoglobulina/genética , Inmunofenotipificación , Leucemia Linfocítica Crónica de Células B/diagnóstico , Leucemia Linfocítica Crónica de Células B/genética , Linfocitosis/genética , Masculino , Hipermutación Somática de InmunoglobulinaRESUMEN
The diagnosis and follow-up process of adult patients with acute myeloid leukaemia (AML) is challenging to clinicians and laboratory staff alike. While several sets of recommendations have been published over the years, the development of high throughput screening and characterization for both genetic and epigenetic events have evolved with astonishing speed. Here we attempt to provide a practical guide to diagnose and follow adult AML patients with a focus on how to balance the wealth of information on the one hand, with the restriction put on these processes in terms of time, feasibility and economy when caring for these patients, on the other.
Asunto(s)
Genómica/métodos , Leucemia Mieloide Aguda/diagnóstico , Biomarcadores de Tumor/metabolismo , Biopsia con Aguja , Médula Ósea/patología , Análisis Citogenético , Citometría de Flujo/métodos , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Cuidados a Largo Plazo/métodos , Neoplasia Residual , Pronóstico , Inducción de Remisión , Factores de RiesgoRESUMEN
The exact disease state of chronic myeloid leukaemia (CML) patients in deep molecular remission is unknown, because even the most sensitive quantitative reverse transcription polymerase chain reaction (qPCR) methods cannot identify patients prone to relapse after treatment withdrawal. To elucidate this, CD34(+) stem cell and progenitor cell subpopulations were isolated by fluorescence-activated cell sorting (FACS), and their content of residual Philadelphia positive (Ph(+) ) cells was evaluated in 17 CML patients (major molecular response, n = 6; 4-log reduction in BCR-ABL1 expression (MR(4) ), n = 11) using both sensitive qPCR and interphase fluorescence in situ hybridization (iFISH). Despite evaluating fewer cells, iFISH proved superior to mRNA-based qPCR in detecting residual Ph(+) stem cells (P = 0·005), and detected Ph(+) stem- and progenitor cells in 9/10 patients at frequencies of 2-14%. Moreover, while all qPCR(+) samples also were iFISH(+) , 9/33 samples were qPCR-/iFISH(+) , including all positive samples from MR(4) patients. Our findings show that residual Ph(+) cells are low BCR-ABL1 producers, and that DNA-based methods are required to assess the content of persisting Ph(+) stem cells in these patients. This approach demonstrates a clinically applicable manner of assessing residual disease at the stem cell level in CML patients in MR(4) , and may enable early and safe identification of candidates for tyrosine kinase inhibitor withdrawal.
Asunto(s)
Proteínas de Fusión bcr-abl/biosíntesis , Leucemia Mielógena Crónica BCR-ABL Positiva/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Citometría de Flujo/métodos , Proteínas de Fusión bcr-abl/genética , Humanos , Hibridación Fluorescente in Situ/métodos , Interfase , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/metabolismo , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Masculino , Persona de Mediana Edad , Neoplasia Residual , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
Real-time quantitative polymerase chain reaction (qPCR) has been extensively validated for the detection of minimal residual disease (MRD) in acute myeloid leukaemia (AML). Meanwhile, multicolour flow cytometry (MFC) has received less attention because the so-called leukaemia-associated immunophenotypes (LAIPs) are generally of lower sensitivity and specificity, and prone to change during therapy. To improve MRD assessment by MFC, we here evaluate the combination of human Myeloid Inhibitory C-type Lectin (hMICL, also termed C-type lectin domain family 12, member A, CLEC12A) and CD 123 (also termed interleukin-3 receptor alpha, IL3RA) in combination with CD34 and CD117 (KIT), as an MRD assay in pre-clinical and clinical testing in 69 AML patients. Spiking experiments revealed that the assay could detect MRD down to 10(-4) in normal bone marrow with sensitivities equalling those of validated qPCR assays. Moreover, it provided at least one MFC MRD marker in 62/69 patients (90%). High levels of hMICL/CD123 LAIPs at the post-induction time-point were a strong prognostic marker for relapse in patients in haematological complete remission (P < 0·001). Finally, in post induction samples, hMICL/CD123 LAIPs were strongly correlated (r = 0·676, P = 0·0008) to applied qPCR targets. We conclude the hMICL/CD123-based MFC assay is a promising MRD tool in AML.
Asunto(s)
Antígenos CD34/metabolismo , Subunidad alfa del Receptor de Interleucina-3/metabolismo , Lectinas Tipo C/metabolismo , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/metabolismo , Antígenos Comunes de Leucocito/metabolismo , Neoplasia Residual/diagnóstico , Proteínas Proto-Oncogénicas c-kit/metabolismo , Receptores Mitogénicos/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Médula Ósea/patología , Niño , Femenino , Humanos , Inmunofenotipificación , Leucemia Mieloide Aguda/genética , Masculino , Persona de Mediana Edad , Pronóstico , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Adulto JovenRESUMEN
Within recent years, many precision cancer medicine initiatives have been developed. Most of these have focused on solid cancers, while the potential of precision medicine for patients with hematological malignancies, especially in the relapse situation, are less elucidated. Here, we present a demographic unbiased and observational prospective study at Aalborg University Hospital Denmark, referral site for 10% of the Danish population. We developed a hematological precision medicine workflow based on sequencing analysis of whole exome tumor DNA and RNA. All steps involved are outlined in detail, illustrating how the developed workflow can provide relevant molecular information to multidisciplinary teams. A group of 174 hematological patients with progressive disease or relapse was included in a non-interventional and population-based study, of which 92 patient samples were sequenced. Based on analysis of small nucleotide variants, copy number variants, and fusion transcripts, we found variants with potential and strong clinical relevance in 62% and 9.5% of the patients, respectively. The most frequently mutated genes in individual disease entities were in concordance with previous studies. We did not find tumor mutational burden or micro satellite instability to be informative in our hematologic patient cohort.
RESUMEN
Handling of large data sets from whole exome sequencing is a challenge, not the least because of the high risk of detecting false positive variants. Furthermore, there is still no consensus regarding what stage filtering of variants is performed in the bioinformatics pipeline to produce consistent result sets, the extent of filtering and how this is most optimal performed. We hypothesized that combination of coding transcriptome and exomes enables precise identification of both somatic single nucleotide and indel variants early in the bioinformatics process, superseding the need for extensive annotation and validation from external databases. Exome and RNA-sequencing were performed on diagnosis-remission paired bone marrow samples from 5 cytogenetically normal AML, i.e. sequencing of 20 samples in total. Intersection of rare exome and RNA variants, exclusively found in the diagnostic samples, yielded a median of 6 somatic point mutations and small indels, ranging from 3 to 21. Close correlation between routine diagnostic biomarkers was observed in 29/30 laboratory tests, with the exception of a large FLT3 internal tandem repeat, whereas WT1 with nonsense mutation lacked RNA transcripts. Additionally, the assay revealed mutations in DNMT3A, IDH2, TET2 and IL32 frame shift, not encompassed by routine panel. We thus describe a procedure to effectively reduce observations to a focused subset of high specificity. The approach is applicable to precise screening of both putative driver mutations and, often heterogeneous, discrete patient specific somatic combinations.
Asunto(s)
Biología Computacional/métodos , Exoma/genética , Leucemia/genética , Análisis de Secuencia de ADN/métodos , Análisis de Secuencia de ARN/métodos , Enfermedad Aguda , Biología Computacional/tendencias , Bases de Datos Genéticas , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Mutación INDEL , Mutación Puntual , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Stable flow cytometric markers for malignant myeloid cells are highly warranted. Based on data from stem cell research, we hypothesized that the human inhibitory C-type lectin like receptor (hMICL) might represent a novel diagnostic and prognostic vehicle in a standard flow cytometry (FCM) setting. METHODS: Standard four-color FCM was employed to uncover the expression patterns of hMICL in bone marrow in a test set of 55 retrospectively collected diagnostic acute myeloid leukemia (AML) samples and in a set of 36 prospectively collected diagnostic AML samples. RESULTS: Ninety-two percent of the AML patients stained positive for hMICL and in the otherwise poorly characterized CD34 negative patient group hMICL staining revealed a very homogenous expression profile in the blast cell compartment with a mean of 88% hMICL positive cells. Moreover, hMICL displayed significantly higher expression in AML as compared with normal donors as measured by median fluorescence intensity (MFI) ratios (P = 0.01). There was no difference in hMICL MFI ratios between the CD34 positive and the CD34 negative subgroups (P = 0.89). Importantly, there was no difference in MFI ratios between paired diagnostic and relapse samples (P = 0.76) in 23 cases studied, indicating stable expression of hMICL during the course of the disease. In contrast to the other stem cell associated antigens analyzed (CD34, CD96, CD117, and CD133), hMICL was expressed on myeloid blast cells only, revealing hMICL as a diagnostic marker in AML. CONCLUSION: These data identify hMICL as a myeloid leukemia-associated antigen and establishes its applicability for diagnosis and follow-up of AML patients in a standard FCM setting.
Asunto(s)
Lectinas Tipo C/metabolismo , Leucemia Mieloide Aguda/diagnóstico , Receptores Mitogénicos/metabolismo , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Crisis Blástica/metabolismo , Crisis Blástica/patología , Recuento de Células , Femenino , Citometría de Flujo/métodos , Estudios de Seguimiento , Humanos , Inmunofenotipificación , Leucemia Mieloide Aguda/metabolismo , Leucocitos Mononucleares/metabolismo , Leucocitos Mononucleares/patología , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Adulto JovenRESUMEN
Reactivation of human cytomegalovirus (HCMV) remains a serious problem in immunosuppressed individuals. To investigate whether a change in the immune status can be used as an earlier marker for HCMV reactivation than the traditional PCR analysis, eight chronic lymphocytic leukemia (CLL) patients at risk for reactivation due to commencement of alemtuzumab (anti-CD52) treatment were longitudinally followed. Five series of consecutive weekly blood samples were immunophenotyped by flow cytometry to cover both the innate and adaptive immune responses. Concurrently, patients were monitored by PCR for HCMV reactivation. We found a minor upregulation of the early activation marker CD69 on NK cells immediately before HCMV was detected in circulation by PCR. Interestingly, for the specific immune response, CD69 was highly upregulated on CD3(+) T cells, especially for the CD8(+) subset, in the two patients experiencing an HCMV reactivation between 6 and 20 d before HCMV viremia was measured by PCR. Moreover, a CD4(+):CD8(+) ratio lower than 0.6 may indicate a trend toward an increased risk for viral reactivation. In conclusion, an increase in CD69 expression is a promising candidate as an early predictor of HCMV reactivation.
Asunto(s)
Antígenos CD/análisis , Antígenos de Diferenciación de Linfocitos T/análisis , Infecciones por Citomegalovirus/diagnóstico , Lectinas Tipo C/análisis , Leucemia Linfocítica Crónica de Células B/complicaciones , Linfocitos T/inmunología , Activación Viral/inmunología , Anciano , Alemtuzumab , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados , Anticuerpos Antineoplásicos/uso terapéutico , Biomarcadores , Complejo CD3/análisis , Relación CD4-CD8 , Citomegalovirus/inmunología , Infecciones por Citomegalovirus/inmunología , Femenino , Citometría de Flujo , Humanos , Huésped Inmunocomprometido , Factores Inmunológicos/uso terapéutico , Células Asesinas Naturales/química , Células Asesinas Naturales/inmunología , Masculino , Persona de Mediana Edad , Linfocitos T/químicaRESUMEN
We have examined natural killer (NK) cell functionality of 54 B-CLL patients upon in vitro stimulation with interleukin-21 (IL-21), together with the anti-CD20 antibody, rituximab. Upon stimulation with rituximab-coated target cells IFN-γ production was reduced in patients' NK cells compared to healthy donors', while both natural- and antibody-dependent cytotoxicity (ADCC) was normal. Following additional stimulation with IL-21, IFN-γ production, natural cytotoxicity and ADCC were significantly augmented in patients. A complete restoration of IFN-γ production, however, required the depletion of malignant cells prior to stimulation. Collectively, our data show that NK cells of B-CLL patients are reversibly inhibited, but that their functionality can be normalized by stimulation with IL-21 and when inhibitory effects of the malignant B-CLL cells are eliminated by depletion.
Asunto(s)
Anticuerpos Monoclonales de Origen Murino/farmacología , Linfocitos B/efectos de los fármacos , Interleucinas/farmacología , Células Asesinas Naturales/efectos de los fármacos , Leucemia Linfocítica Crónica de Células B/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Citotoxicidad Celular Dependiente de Anticuerpos , Linfocitos B/inmunología , Linfocitos B/metabolismo , Estudios de Casos y Controles , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Femenino , Citometría de Flujo , Humanos , Factores Inmunológicos/farmacología , Interferón gamma/metabolismo , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/metabolismo , Masculino , Persona de Mediana Edad , RituximabAsunto(s)
Antígenos CD/sangre , Antígenos de Diferenciación Mielomonocítica/sangre , Biomarcadores de Tumor , Leucemia Linfocítica Crónica de Células B/sangre , Leucemia Linfocítica Crónica de Células B/mortalidad , Receptores de Superficie Celular/sangre , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Aberraciones Cromosómicas , Ensayo de Inmunoadsorción Enzimática , Humanos , Inmunofenotipificación , Estimación de Kaplan-Meier , Leucemia Linfocítica Crónica de Células B/diagnóstico , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Pronóstico , Resultado del TratamientoRESUMEN
Human cytomegalovirus (HCMV) manipulates the host immune system in various ways. Allegedly, HCMV infection is associated with increased percentages of a particular natural killer (NK) cell subset expressing the activating receptor CD94/NKG2C in both healthy individuals and in patients infected with human immunodeficiency virus (HIV). Whether the HCMV-mediated induction of this specific NK cell subset is also apparent for other diseases characterized by abnormal immune responses, such as malignant blood diseases, is unknown. By comparing the fractions of CD94/NKG2C(+) NK cells in B-cell chronic lymphocytic leukemia (B-CLL) patients having either positive or negative HCMV serostatus, a proportional increase of this cell subset was obvious in the HCMV-seropositive subjects. Therapeutic intervention in the patients with positive HCMV serostatus did not seem to reduce the percentage of CD94/NKG2C-expressing NK cells. Thus, HCMV infection seemingly shapes the NK cell system in healthy individuals, HIV patients, and B-CLL patients in a uniform manner, even though these involve different immunological challenges.