The translocation (1;14)(p34;q11) in human t‐cell leukemia: Chromosome breakage 25 kilobase pairs downstream of the tal1 protooncogene

Abstract

Nearly 30 percent of patients with T-cell acute lymphoblastic leukemia (T-ALL) exhibit a tumor-specific rearrangement of the TAL1 gene (also called TCL5 or SCL). These rearrangements are generated by either local DNA deletion or a (1;14)(p34;q11) chromosome translocation, and they typically result in structural alterations of the TAL1 transcription unit. In this report we present a molecular characterization of the t(1;14)(p34;q11) from a T-ALL patient. As a consequence of the translocation, TAL1 is transposed from its normal position on chromosome 1 into the T-cell receptor alpha/delta chain locus on chromosome 14. Unlike previous cases, the chromosome 1 breakpoint in this patient did not disrupt the continuity of the TAL1 transcription unit, but instead occurred approximately 25 kilobase pairs (kb) downstream of TAL1. This observation suggests that malignant alteration of TAL1 can be mediated by long-range cis-activating mechanisms that are triggered by DNA rearrangement at a distant site. Genes Chrom Cancer 4:211-216 (1992).

Genomic characterization of pediatric T-cell acute lymphoblastic leukemia reveals novel recurrent driver mutations

“…We identified several structural chromosomal abnormalities within our cohort (Figure 1 and Supplemental Information). Mature T-ALL patients 547, 759 and 636 were shown to carry translocations t(1;14)(p34;q11), t(11;14)(p13;q11) and t(10;14)(q24;q11) respectively, leading to the juxtaposition of the TAL1 , LMO2 and TLX1/HOX11 oncogenes to the T-cell receptor alpha/delta ( TCRA/D ) at locus 14q11 [ 18 – 20 ]. We also identified a rarer translocation t(1;7)(p32;q34)/TRB-TAL1 in the mature T-ALL patient 849 [ 9 ] as well as the well-known t(10;11)(p12;q14) CALM-AF10 translocation in both ETP-ALL cases 791 and 879 and a t(9;22)(q34;q11.2)/BCR-ABL in the immature T-ALL patient 748 which is very rare in T-ALL (∼1%) [ 21 , 3 ].…”

The TAL1 complex targets the FBXW7 tumor suppressor by activating miR-223 in human T cell acute lymphoblastic leukemia

“…It also targets several downstream oncogenes, including MYB, TRIB2, and STAT5A (Sanda et al, 2012). Although several other genes have been identified as direct targets of TAL1 and its regulatory partners in human T-ALL, such as pre-T cell receptor DISCUSSION The t(1;14)(p34;q11) translocation involving TAL1 in T-ALL was first described over 20 yr ago (Finger et al, 1989;Bernard et al, 1990;Xia et al, 1992), yet the mechanisms through which TAL1 is able to transform thymocytes are only beginning to be dissected. Studies from our laboratory and others using ChIP-seq analysis have shed light on the regulatory networks activated during malignant transformation by TAL1 (Wilson  (pT), aldehyde dehydrogenase 1 member A2 (ALDH1A2), NK3 homeobox 1 (NKX3-1), and cyclin-dependent kinase 6 (CDK6), the relative contributions of these targets to leukemogenesis remain unclear (Bernard et al, 1998;Ono et al, 1998;Herblot et al, 2000;Palomero et al, 2006;Kusy et al, 2010;Palii et al, 2011;Sanda et al, 2012).…”

Z-DNA, an active element in the genome

“…Interestingly, multiple alternating purine-pyrimidine Z-DNA-forming regions have been found near the c-MYC P1 promoter and the 3' downstream region (79,80) near these breakpoints. The SCL gene (also known as TCL5 or tal-1) dysregulation can result from joining SCL to the TCRD or TCRB gene in t(1;14) or t(1;7) translocations, and are the most common chromosomal abnormality associated with T-cell acute lymphoblastic leukemia (ALL), found in ~30% of patients with childhood T-cell ALL (81). A translocation breakpoint cluster region and a 90-kb deletion region are found 5' to the coding region of the SCL gene.…”