RESUMO
Staging systems and laboratory features help predict survival in chronic lymphocytic leukaemia but they do not distinguish patients who will progress from those whose disease will remain indolent. CD38 expression has emerged as an independent prognostic factor, yet there is debate as to what level of CD38 affects prognosis. We plotted the hazard ratios for the treatment-free interval (TFI) between the higher and lower groups defined by CD38 cut-offs from 0 to 100%. The maximum hazard ratio was achieved for a cut-off of 7%. We examined by triple colour analysis the values for CD38 in 289 untreated patients using both >or=30 and >or=7% as thresholds for prognosis. Using a >or=7% threshold (but not >or=30%), we showed a significant correlation with advanced stage and male sex. The interval from diagnosis to first therapy or TFI was longer (median 36 months) in patients with <7% CD38 positive cells than those with >or= 30% (8.7 months) or with intermediate values between 7 and 29% (P<0.00005). The <7% threshold also identified patients in stage A with a long TFI (P=0.0001). Multivariate analysis showed that CD38 has independent prognostic value for TFI in all patients. In 135 patients tested for deletions of p53, 13q14 and 11q23 and for trisomy 12, we showed a correlation between 13q14 deletion and <30%/<7% CD38 positive cells and a tendency for trisomy 12 to be associated with >or=30%/>or=7% CD38 positive cells. We conclude that 7% may be a more useful threshold for disease progression than higher values of CD38.
Assuntos
ADP-Ribosil Ciclase/imunologia , Antígenos CD/imunologia , Biomarcadores Tumorais , Regulação Leucêmica da Expressão Gênica/genética , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/imunologia , ADP-Ribosil Ciclase 1 , Adulto , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/imunologia , Aberrações Cromossômicas , Cromossomos Humanos Par 11/genética , Cromossomos Humanos Par 12/genética , Cromossomos Humanos Par 13/genética , Feminino , Regulação Leucêmica da Expressão Gênica/imunologia , Humanos , Imunofenotipagem , Leucemia Linfocítica Crônica de Células B/patologia , Masculino , Glicoproteínas de Membrana , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Resultado do Tratamento , Proteína Supressora de Tumor p53/genéticaRESUMO
We evaluated the presence of P-glycoprotein (P-gp)-170, multidrug resistance protein (MRP), lung resistance protein (LRP)-56 and Bcl-2 in CD19-positive cells from 100 cases of chronic lymphocytic leukaemia (CLL). P-gp-170 was found in 73% of the CLL cases with no significant difference regarding stage or previous treatment. LRP-56 protein was homogeneously distributed with no differences for stage or treatment. MRP protein was detected at a low level of expression in 49.4% of CLL patients with no differences for stage or treatment. Bcl-2 protein was expressed at a high level in all CLL patients and higher levels were found in the advanced stage. This leads us to conclude that P-gp, MRP, LRP-56 and Bcl-2 are frequently expressed in CLL. P-gp, MRP and LRP are not correlated to stage or previous treatment. Bcl-2 is higher in advanced-stage patients. The clinical and biological significance of these zMDR mechanisms in CLL remains to be fully explained.