Comparison of ID4 amino acid sequences and RNA expression in BCP-ALL. (A) Protein sequence comparison of the human ID proteins. The region of highest homology between ID family proteins is within the HLH region (box 2), although there are other small areas of homology (boxes 1, 3, and 4). An amino-terminal CDK2-dependent phosphorylation site has been identified (SPVR) in all IDs except ID1 (box 1).⁸⁶  All members except ID3 contain a D-box region (RXXLXXXN in box 3) that targets the protein for proteosomal degradation.⁴⁸  Phosphorylation status may have implications for nuclear localization and cell-cycle effect of ID proteins.^86,87  (B) Dendrogram from unsupervised clustering of gene expression data obtained from 106 cases of pediatric BCP-ALL lacking ETV6-RUNX1, BCR-ABL, or MLL-AF4 chromosomal translocations showing clustering of cases with high-level ID4 expression. (G.C., T.A., R.S., and M.J.S.D., unpublished observations, August 2008). Hierarchical clustering analysis was carried out considering only those clones that had a 2-fold difference in expression from the mean on at least 2 arrays (4421 clones). Each column represents one sample. The expression of ID4 is displayed as a variation in color as indicated in the lower right corner. Gray represents data that were omitted because they were not well measured.