Clustering of the breakpoints and dysregulated expression of the HOXA genes in leukemias with TCRB-HOXA rearrangement. (A) The 4 breakpoints cluster in a 2.6-kb breakpoint cluster region (BCRHOXA) as indicated. The direction of transcription is shown by arrows (centromere to telomere for the HOXA genes, and opposite direction for EVX1). Transcription products of the HOXA genes are drawn according to the data of the UCSC site. The HOXA10B exons are shown as red boxes. The rearrangements disrupt the HOXA locus at the 3′ end of HOXA10 gene (cases TL44, TL45, and TL46), and within the intron Ib region of HOXA9 (TL43), as indicated. Open reading frames are shown as black boxes. The 2 isoforms of the HOXA10 protein (HOXA10A, quoted HOXA10, and HOXA10B) are drawn according to previous reports, and the homeobox DNA-binding domain is indicated.^32-34  (B) Analysis of expression of the HOXA genes by specific real-time RT-PCR in T-ALL samples. The HOXA and EVX1 expression values are shown in the 4 HOXA-rearranged cases (marked t), and the 2 HOXA-related cases without detected chromosomal rearrangement (TL47 and TL48, marked ^*), which constitute the HOXA_R group. Values in the 3 MLL-rearranged cases, the 4 CALM-AF10 cases, a panel of TAL_R and TLX1/TLX3 samples, T-cell lines, normal human thymus, and normal bone marrow samples are shown. HOXA9B and HOXA10B transcripts were also analyzed (bottom rows). Median normalized Ct values are indicated and a color scale was used as shown.