MUTATIONS OF RETINOBLASTOMA GENE (Rb-1) AS A PROGNOSTIC FACTOR IN CHILDREN WITH ACUTE LEUKEMIA AND NEUROBLASTOMA

Abstract

Rb-1 is a tumor suppressor gene encoding for a nuclear phosphoprotein acting as a cell cycle regulator, normally expressed in hematopoietic cells and more often inactivated by point mutations with predominance for exons 20-24. The aim of this study is to correlate the retinoblastoma-1 (Rb-1) gene mutations with the prognosis and progression of childhood acute leukemia and neuroblastoma. Bone marrow slides from 26 children with leukemia (18 acute lymphoblastic leukemia [ALL] and 8 acute myeloid leukemia [AML]) and 4 children with neuroblastoma were studied. Exons 20, 21, and 22 were amplified using the polymerase chain reaction technique. Single strand conformational polymorphism (SSCP) and heterodoublex analysis were performed to detect mutations. In ALL cases, two samples in exon 20 (11.11%), one in exon 21 (5.56%), and four in exon 22 (22.22%) had altered conformation. All but one of these cases were classified as high-risk leukemia patients who either relapsed or never achieved remission. Two of the AML cases who did not achieve remission and one of the neuroblastoma cases with concomitant bone marrow infiltration had altered conformation as well. The SSCP and heterodoublex analysis showed that all but one who did not belong to the high-risk group had the same altered conformation. These data suggest that Rb-1 gene could possibly be used as an independent prognostic factor for the acute leukemia of childhood and result in the intensification of chemotherapy. In solid tumors with bone marrow involvement it could play a role as a marker of aggressive disease.

Alterations of Rb Pathway Components Are Frequent Events in Patients with Oral Epithelial Dysplasia and Predict Clinical Outcome in Patients with Squamous Cell Carcinoma

“…Loss of pRb expression has been associated with shorter disease-free survival in astrocytomas [39], non-Hodgkin’s lymphomas [40] and neuroblastomas [41]. In fact, our group has shown earlier that loss of pRb expression is associated with adverse disease outcome in oral SCCs in a different and smaller cohort of patients [15].…”

Cell Division Rates of Primary Human Precursor B Cells in Culture Reflect In Vivo Rates

“…Because expansion is dictated, in part, by cell division, regulation of this cell function is likely perturbed in many precursor B lymphoblastic leukemias. In support, mutations or aberrant expression of the cell-cycle regulatory genes INK4A, INK4B, retinoblastoma, and possibly p21(CIP1/WAF1/SDI1) are frequently seen in both pediatric and adult precursor B lymphoblastic leukemias [24][25][26][27][28][29]. In pediatric leukemias, low rate of cell division and high expression of INK4A may be associated with in vitro drug resistance or poor clinical outcome [12,13,30].…”

Foetal haemoglobin-blood cells (F-cells) as a feature of embryonic tumours (blastomas)

“…All have similar morphology, with uniform, primitive embryonic, blastoma cells. Some of them are reported to share the same oncogenes, as WT1 in Wilms' tumour (Maiti et al, 2000), in retinoblastoma (Wagner et al, 2002) and in acute myeloid leukaemia (King-Underwood et al, 1996), and RB1 in retinoblastoma (Sanchez et al, 2000), neuroblastoma (Markaki et al, 2001), childhood leukaemia (Markaki et al, 2001) and Ewing's sarcoma (Cope et al, 2001). We evaluated HbF as a cancer marker in those diseases by examining the histological distribution of F-cells in the tumours and bone marrow of those patients, noting their concentrations and locations.…”