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

Interstitial deletion or loss of chromosome 5, del(5q) or -5, is a frequent finding in myeloid leukemias and myelodysplasias, suggesting the presence of a tumor suppressor gene within the deleted region. In our search for thi s gene, we identified a candidate, 5qNCA (LOC51780), which lies within a co nsistently-deleted segment of 5q31. 5qNCA expresses a 7.2-kb transcript wit h a 5286-bp open reading frame which is present at high levels in heart, sk eletal muscle, kidney, placenta, and liver as well as CD34+ cells and AML c ell lines. 5qNCA encodes a 191-kD nuclear protein which contains a highly-c onserved C-terminus containing a zinc finger with the unique spacing Cys-X2 -Cys-X7-His-X2-Cys-X2-Cys-X4-Cys-X2-Cys and a jmjC domain, which is often f ound in proteins that regulate chromatin remodeling. Expression of 5qNCA in a del(5q) cell line results in suppression of clonogenic growth. Prelimina ry sequence results in AML and MDS samples and cell lines has revealed a po ssible mutation in the KG-1 cell line resulting in a THR to ALA substitutio n that has not been found in over 100 normal alleles to date. We propose 5q NCA is a good candidate for the del(5q) tumor suppressor gene based on its predicted function and growth suppressive activities, and suggest that furt her mutational and functional study of this interesting gene is warranted.