Argyrophilic nucleolar organizer region counts and prognosis in multiple myeloma

Abstract

The prognostic significance of argyrophilic nucleolar organizer regions (AgNORs) has been evaluated in bone marrow trephine biopsies from 64 patients with multiple myeloma (MM) prior to therapy. The univariate Kaplan-Meyer survival analysis showed a significant correlation between survivals and AgNOR counts (median of survival 51.3 months for cases with < or = 4.62 AgNORs per plasma cell (PC) versus 16 months for cases with > 4.62 AgNORs per PC; P = 0.0000) or AgNOR distribution in PC nucleus (AgNOR configuration) (median of survival 71.67 months for cases with tightly grouped AgNORs, 16.26 for partially grouped and 11.74 for dispersed AgNORs; P = 0.001). Significant prognostic correlations were also found for monoclonal immunoglobulin type (P = 0.008), platelet counts (P = 0.0078), serum creatinine level (P = 0.0001), Durie's clinical stage (P = 0.02), percentage of plasma cells in bone marrow biopsies (BMPC%) (P = 0.005), pattern of medullary involvement (P = 0.003) and PC atypia (P = 0.009). Borderline result was detected for the percentage of PCs in aspirates (P = 0.06). No significant correlation was found between prognosis and patients age, sex, haemoglobin level, serum albumin or calcium level, marrow cellularity and excess of haemosiderin. Multivariate survival analysis showed that only two variables were significantly correlated with prognosis: AgNOR counts (P = 0.003) and AgNOR configuration (P < 0.001). In addition, the analysis of variance showed significant association between AgNOR number and platelet counts, haemoglobin level, calcaemia, creatininaemia, clinical stage, percentage of PCs in aspirates, BMPC%, pattern of medullary involvement, PC atypia, marrow cellularity and configuration of AgNORs. Our results indicate that AgNOR counts and configuration have prognostic and diagnostic value and therefore they are useful independent parameters to assess the pretherapeutic aggressiveness of multiple myeloma.

Bax expression has prognostic significance that is enhanced when combined with AgNOR counts in glottic carcinomas

“…Most of the previous studies on squamous cell carcinomas of the head and neck have used the mAgNOR counting method (Pich et al 1991: Sano et al 1991: Bockmil et al 1992: Hirsch et al 1992. These studies show variation in overall mAgNOR count ranging from 4.3 to 15.1 (Bockmdl et al 1992: Hirsch et al 1992).…”

Structural features of nucleoli in blood, leukemic, lymphoma and myeloma cells

“…Such cells might correspond to aging non-proliferating leukemic blasts which were reported in earlier studies (see Smetana et al, 1996). As in other malignant diseases, in malignant lymphoproliferative disorders and multiple myeloma, the increased number of AgNORs is usually associated with a more aggressive and rapid course of the disease (Crocker 1992;Pich et al, 1992;Mikou, 1993;Kalir et al, 1994. At this point, it should be mentioned that a high percentage of leukemic lymphocytes in chronic lymphocytic leukemia possess ring-shaped nucleoli with the re-distributed silver stained proteins at fibrillar centers, similar to stimulated lymphocytes at the end of the early G1 phase.…”

The snoRNA target of t(4;14) in multiple myeloma regulates ribosome biogenesis

“…NORs are the structural and functional units of the nucleolus, where ribosomal DNA genes are clustered. 33 Together these data provide evidence that ACA11 overexpression drives a key nucleolar phenotype in MM associated with t(4;14) chromosomal translocation and poor outcomes. Thus, NOR area is directly associated with both nucleolar area and rRNA transcription.…”

“…32 In addition, higher NOR counts in MM patients are directly associated with poorer survival. 33 Together these data provide evidence that ACA11 overexpression drives a key nucleolar phenotype in MM associated with t(4;14) chromosomal translocation and poor outcomes.…”