A novel nuclear protein, 5qNCA (LOC51780) is a candidate for the myeloid leukemia tumor suppressor gene on chromosome 5 band q31

Abstract

Interstitial deletion or loss of chromosome 5, del(5q) or 75, is a frequent ®nding in myeloid leukemias and myelodysplasias, suggesting the presence of a tumor suppressor gene within the deleted region. In our search for this gene, we identi®ed a candidate, 5qNCA (LOC51780), which lies within a consistently-deleted segment of 5q31. 5qNCA expresses a 7.2-kb transcript with a 5286-bp open reading frame which is present at high levels in heart, skeletal muscle, kidney, placenta, and liver as well as CD34+ cells and AML cell lines. 5qNCA encodes a 191-kD nuclear protein which contains a highly-conserved C-terminus containing a zinc ®nger with the unique spacing Cys-X2-Cys-X7-His-X2-Cys-X2-Cys-X4-Cys-X2-Cys and a jmjC domain, which is often found in proteins that regulate chromatin remodeling. Expression of 5qNCA in a del(5q) cell line results in suppression of clonogenic growth. Preliminary sequence results in AML and MDS samples and cell lines has revealed a possible mutation in the KG-1 cell line resulting in a THR to ALA substitution that has not been found in over 100 normal alleles to date. We propose 5qNCA is a good candidate for the del(5q) tumor suppressor gene based on its predicted function and growth suppressive activities, and suggest that further mutational and functional study of this interesting gene is warranted. Oncogene (2001) 20, 6946 ± 6954.

KDM3B Is the H3K9 Demethylase Involved in Transcriptional Activation of lmo2 in Leukemia

“…The reason for this difference is not clear. However, the human KDM3B gene is located at 5q31, and this region is frequently deleted in AML and myelodysplasia (14). It has been previously reported that there is a clear difference in gene expression patterns between AML and ALL.…”

Comprehensive array CGH of normal karyotype myelodysplastic syndromes reveals hidden recurrent and individual genomic copy number alterations with prognostic relevance

“…The deletion includes all candidate ts genes described so far in this region: CTNNA, 23 EGR1 24 and HSPA9, which shows increased expression during EPO-induced erythroid differentiation. 25,26 In addition, other genes involved in cell cycle regulation, CDC25C and CDC23, and in chromatin modification, JMJD1B, a lysine-specific histone demethylase and previously described candidate ts gene from 5q 27 are localized in this segment. A recently described study of exon sequencing for all genes from this segment revealed no mutations in any of these genes, 28 further supporting the notion that the haploinsufficiency of one or more genes from this interval is the disease mechanism.…”

RIL, a LIM Gene on 5q31, Is Silenced by Methylation in Cancer and Sensitizes Cancer Cells to Apoptosis

“…RIL is distal to interleukin-9 and just 250 kb telomeric to the IRF-1, a gene proposed as the 5q31.1 TSG (16) but not altered and expressed in majority of cases and thus unlikely involved. A large number of other candidate TSGs for 5q31 region have been proposed recently, including 5qNCA, ETF1, PURA, HSPA9, CDC23, TTID, and SMAD5, but none of them seem to be mutated or frequently down-regulated (27)(28)(29)(30)(31)(32)(33)(34). It has previously been proposed that the gene involved in 5q31 is not a classic TSG where the remaining allele is inactivated due to mutations in coding sequence or small deletions, but rather, it is silenced by other mechanisms, perhaps by aberrant methylation (14).…”