Altered expression of retinoblastoma protein‐interacting zinc finger gene, RIZ, in human leukaemia

Abstract

Summary. The retinoblastoma protein-interacting zinc finger gene (RIZ), a member of the nuclear protein methyltransferase superfamily, is characterized by the presence of the N-terminal PR domain. The RIZ gene encodes for two proteins, RIZ1 and RIZ2. While RIZ1 contains the PR (PRDI-BF1 and RIZ homologous) domain, RIZ2 lacks it. RIZ gene expression is altered in a variety of human cancers and RIZ1 is now considered to be a candidate tumour suppressor. To investigate the role of RIZ in leukaemogenesis, we analysed the differential expression of RIZ1 and RIZ2 by quantitative real-time reverse-transcription polymerase chain reaction assay. Our results showed that the expression of RIZ1 was significantly decreased in leukaemia cell lines (14 out of 17, 82%) and in patients with acute myeloblastic leukaemia (eight out of 14, 57%). In contrast, RIZ2 expression was increased in patients with acute lymphoblastic leukaemia (eight out of 11, 73%), compared with normal bone marrow cells. These findings indicate that suppression of RIZ1 expression or enhancement of RIZ2 expression may have an important role in leukaemogenesis.

A potential role for PRDM12 in the pathogenesis of chronic myeloid leukaemia with derivative chromosome 9 deletion

“…3 In addition, structural rearrangement, mutation and/or aberrant expression of RIZ, MDS-EVI1 and MEL1 have been reported in myeloid malignancies. 4,7,9 PRDM family members share the feature of expressing two protein products that differ in the presence or absence of the PR domain. 5 Studies of RIZ, MDS-EVI1, MEL1 and BLIMP-1 have revealed that a variety of tumour types often overexpress the PR domain-negative product, relative to the fulllength protein.…”

“…1 The deletions, detected by fluorescent in situ hybridisation (FISH) using large commercial contig probes, were associated with rapid progression to blast crisis and short survival. A recent study by Kolomietz et al 2 used quantitative PCR to demonstrate that a further subset of der (9) deletions exist beyond the resolution of large commercial FISH probes. Subsequent mapping of the microdeletions identified a minimal commonly deleted region (CDR) of 120 kb, associated with short survival.…”

“…Recently, it was established that deletions of over 300 kb occur on the derivative chromosome 9 [der (9)] in approximately 15% of CML patients. 1 The deletions, detected by fluorescent in situ hybridisation (FISH) using large commercial contig probes, were associated with rapid progression to blast crisis and short survival.…”

“…Ph der [9] der [7] der [9] der [7] der [9] der [9] 395P 17 WCP7 , mapping approximately 3 Mb centomeric to ABL, hybridises to both homologues of chromosome 9 and is therefore proximal to the inserted chromosome 9 segment. (d) BAC bA395P17 (red) hybridised to chromosome 7 (blue), and not the der(9), therefore representing a region contained within the inserted segment.…”

“…Unfortunately, there was insufficient archived material from this patient on which to define the precise genomic rearrangements. [7] der [9] ABL BCR WCP7 Chr 9 Chr 7 Chr 22 der [7] der [9] der [22] ins(9:7) t(9:22) 7 57C19 9 9…”