RESUMEN
BACKGROUND: Zeta-chain associated protein (ZAP)-70 has been proposed as a surrogate marker for immunoglobulin heavy-chain variable region (IgVH) mutation in chronic lymphocytic leukemia (CLL), but it is still not clear whether it is an independent prognostic factor. METHODS: The authors evaluated ZAP-70 expression by flow cytometry in 201 untreated patients and correlated ZAP-70 levels with CD38 expression, genetic abnormalities detected by fluorescence in situ hybridization (FISH), and the time from diagnosis to first treatment. RESULTS: Fifty-seven patients (28%) were positive for ZAP-70 (> or = 20%). Positive ZAP-70 status was associated with advanced disease stage, atypical morphology, CD38-positive status, trisomy 12, del(6q), or no detectable abnormalities; negative ZAP-70 status was correlated with del(13q) as a sole abnormality. The treatment-free interval (TFI) was 17.7 months for ZAP-70-positive patients and 44.6 months for ZAP-70-negative patients (P < 0.001). Multivariate analysis in 117 patients identified advanced stage, CD38 > or = 7%, and the absence of del(13q) as a sole abnormality as independent factors for short TFI. Excluding FISH, ZAP-70 status acquired independent prognostic value along with CD38 status. The authors proposed a risk model that combines ZAP-70 and CD38 to identify patients who are likely to progress. When both markers were positive, the TFI was 12 months; when both were negative, the median TFI was 54 months; a median TFI of 26 months was observed in patients who had discordant results (P < 0.00001). CONCLUSIONS: The current findings suggested that both ZAP-70 and CD38 should be tested prospectively in all patients with early-stage CLL.
Asunto(s)
ADP-Ribosil Ciclasa 1/biosíntesis , Biomarcadores de Tumor/análisis , Leucemia Linfocítica Crónica de Células B/metabolismo , Leucemia Linfocítica Crónica de Células B/terapia , Proteína Tirosina Quinasa ZAP-70/biosíntesis , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Citometría de Flujo , Humanos , Hibridación Fluorescente in Situ , Leucemia Linfocítica Crónica de Células B/patología , Masculino , Persona de Mediana Edad , Pronóstico , Factores de RiesgoRESUMEN
BACKGROUND AND OBJECTIVES: CD123 is an antibody that identifies the a chain of the human interleukin-3 receptor and is expressed in a variety of normal hematopoietic cells, acute leukemia and hairy cell leukemia (HCL). The aim of the study was to investigate the diagnostic value of CD123 expression in B-cell disorders with circulating hairy and villous lymphocytes. DESIGN AND METHODS: We investigated the diagnostic value of CD123 expression in neoplastic cells from 59 patients with B-cell disorders with circulating hairy or villous lymphocytes: HCL (n=24), the variant form of HCL (n=11) and splenic lymphoma with villous lymphocytes (SLVL) (n=24). Cells from 12 patients with chronic lymphocytic leukemia were used as controls. Immunophenotypic analysis was performed by flow cytometry on 77 samples from peripheral blood (n=48), bone marrow (n=25) and spleen cell suspensions (n=4). RESULTS: Our findings show that cells from 95% of typical HCL express CD123 with strong to moderate intensity while this molecule is absent in circulating cells from most cases of HCL-variant (91%) and SLVL (97%). INTERPRETATION AND CONCLUSIONS: We conclude that CD123 is a useful new marker for distinguishing B-cell disorders with circulating villous lymphocytes as its expression is characteristic of typical HCL with high sensitivity and specificity. However CD123 does not allow the distinction between HCL-variant and SLVL, as both are CD123 negative.
Asunto(s)
Biomarcadores de Tumor/biosíntesis , Leucemia de Células Pilosas/diagnóstico , Leucemia Linfocítica Crónica de Células B/diagnóstico , Linfocitos/metabolismo , Linfoma de Células B/diagnóstico , Receptores de Interleucina-3/biosíntesis , Neoplasias del Bazo/diagnóstico , Anticuerpos Monoclonales/inmunología , Biomarcadores de Tumor/inmunología , Citometría de Flujo , Humanos , Inmunofenotipificación , Subunidad alfa del Receptor de Interleucina-3 , Leucemia de Células Pilosas/inmunología , Leucemia de Células Pilosas/metabolismo , Leucemia Linfocítica Crónica de Células B/inmunología , Leucemia Linfocítica Crónica de Células B/metabolismo , Linfocitos/patología , Linfoma de Células B/metabolismo , Receptores de Interleucina-3/inmunología , Sensibilidad y Especificidad , Neoplasias del Bazo/inmunología , Neoplasias del Bazo/metabolismoRESUMEN
We analyzed by flow cytometry the expression of CD20 and FMC7 in cell suspensions from 932 patients, including 630 cases of chronic lymphocytic leukemia (CLL), 23 cases of other B-cell leukemias, and 279 cases of B-cell non-Hodgkin lymphoma (B-cell NHL). CD20 was positive in 94.5% of cases; FMC7 was positive in 35.7%. There was a correlation between CD20 and FMC7 expression in patients with B-cell NHL (P < .001) but not CLL (P = .1). We also tested a scoring system in which FMC7 was replaced by CD20 and compared it with our current scoring system for CLL. With this modification, the accuracy of the scoring system for differentiating CLL from other non-CLL disorders fell from 94.4% to 81.5%. In CD20+ CLL, the intensity of CD20 expression correlated with FMC7 and low scores (P < .001 for both comparisons). We suggest that the particular conformation of CD20 recognized by FMC7 is manifested only in cells with strong CD20 expression, which is not the case for CLL. FMC7 is of greater diagnostic value than CD20 for distinguishing CLL from other B-cell disorders; we recommend its continued use for this purpose.
