We have studied a leukemic stem-cell line,

The SCL gene, initially discovered at the site of a translocation breakpoint associated with the development of a stem cell leukemia, encodes a protein that contains the highly conserved basic helix-loop- helix (bHLH) motif found in a large array of eukaryotic transcription factors. Recently, we have described a nonrandom, site-specific SCL rearrangement in several T-cell acute lymphoblastic leukemia (ALL) cell lines that juxtaposes SCL with a distinct transcribed locus, SIL. The SIL/SCL rearrangement was found in leukemic blasts from 11 of 70 (16%) newly diagnosed T-cell ALL patients, a prevalence substantially higher than that of the t(11;14) translocation, which has previously been reported as the most frequent nonrandom chromosomal abnormality in T- cell ALL. We did not detect the SIL/SCL rearrangement in the leukemic blasts from 30 patients with B-cell precursor ALL, indicating that the rearrangement was specific for T-cell ALL. Analysis of RNA from these patients indicated that an SIL/SCL fusion mRNA was formed, joining SIL and SCL in a head-to-tail fashion. The fusion occurs in the 5′ untranslated region (UTR) of both genes, preserving the SCL coding region. The net result of this rearrangement is that SCL mRNA expression becomes regulated by the SIL promoter, leading to inappropriate SCL expression. The resultant inappropriate expression of this putative transcription factor may then contribute to leukemic transformation in T-cell ALL.

Figure 2IgH and Ig rearrangement analysis at diagnosis and relapses. Genomic DNA from diagnosis and relapses was subjected to PCR analysis using the FR1c-5Ј and JHc-3Ј IgH-specific primers and using the IRSS-5Ј and Kde-3Ј Ig-specific primers. Both IgH and Igspecific PCR products were spotted in duplicate on to the nylon membrane and hybridized with the patient-specific probe. Mononuclear cells (MNC) from a healthy volunteer donor served as a control. Dotblot results for IgH and Ig are shown in a and b, respectively. because the same IgH chain rearrangement was already present at the onset, while chain gene deletion was detectable at relapse only.This case underlines the important role of comparative studies, mainly at the molecular level, between disease patterns at diagnosis and relapse, as potential means yielding valuable insights into the mechanism of leukemic recurrence. Therapy-related T cell lymphoblastic lymphoma with t(11;19)(q23;p13) and MLL gene rearrangement TO THE EDITORDuring the past several decades, advances in the treatment of childhood cancers have resulted in increased survival of pediatric cancer patients. This is in large part due to the use of aggressive chemotherapy regimens, radiation therapy or a combination of both. However, along with the benefits of increased survival. It has become Correspondence: PD Aplan at his current address: