Occurrence of TEL-AML1 Fusion Resulting from (12;21) Translocation in Human Early B-Lineage Leukemia Cell Lines

  • C. C. Uphoff
  • R. A. F. MacLeod
  • S. A. Denkmann
  • T. R. Golub
  • A. Borkhardt
  • J. W. G. Janssen
  • H. G. Drexler
Conference paper
Part of the Haematology and Blood Transfusion / Hämatologie und Bluttransfusion book series (HAEMATOLOGY, volume 39)


The recurrent (12;21)(p13;g22) translocation fuses the two genes TEL and AML1 that have previously been cloned from translocation breakpoints in myeloid leukemias. Using mainly reverse transcriptase-polymerase chain reaction (RT-PCR), the TEL chimeric transcript has been observed in 22–27% of pediatric patients with acute lymphoblastic leukemia (ALL), in particular in the early B-lineage ALL subtype, making it the most common genetic lesion in these patients. The vast majority of acute myeloid leukemias, other ALL subtypes and even adults with early B-lineage ALL were TEL-AML1-negative. We determined whether the TEL fusion gene can also be observed in leukemia cell lines with an early B-lineage phenotype. Twenty-nine cell lines established from children (n = 13) or adults (n = 13) with early B-lineage ALL and five cell lines derived from chronic myeloid leukemia in blast crisis or B-cell non-Hodgkin’s lymphoma were investigated for the occurrence of the TEL-AML1 rearrangement by RT-PCR. While all 13 adult early B-Iineage ALL cell lines and the five cell lines from other leukemias or lymphomas were negative, 1/13 pediatric cell lines (cell line REH) was found to be positive for TEL though neither reciprocal AML1-TEL,nor normal TEL, mRNA was detectible by RT-PCR in this cell line. These findings agreed with the results of conventional cytogenetic and FISH analysis of REH which carries the der(21) partner only of t(12;21)(p13;q22), probably resulting from a complex translocation, t(4;12;21;16) (q32;p13;q22;q24.3). Hybridization with flanking cosmid clones, covering exons 1 and 8 respectively of TEL,confirmed a rearrangement accompanying the t(12;21), and showed cryptic deletion of the residual allele resulting from an apparently reciprocal t(5;12)(q31;p13). These findings in REH provide a further example of, and possible cytogenetic mechanism for, the paradigm of TEL-AML1 fusion accompanied by deletion of the residual TEL allele. The low rate of early B-lineage ALL cell lines carrying this translo cation contrasts clearly with the relative high frequency of TEL-AML1-positive cases in primary material. It is possible that expression of the fusion product hampers the in vitro growth and establishment in culture of such leukemic cells. The cell line REH represents a useful tool for the further molecular characterization of this unique breakpoint and can serve as a positive control in routine PCR reactions.


Acute Lymphoblastic Leukemia Chronic Myeloid Leukemia Chimeric Transcript Cryptic Deletion Unique Breakpoint 
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Copyright information

© Springer-Verlag Berlin Heidelberg 1998

Authors and Affiliations

  • C. C. Uphoff
    • 1
  • R. A. F. MacLeod
    • 1
  • S. A. Denkmann
    • 1
  • T. R. Golub
    • 2
  • A. Borkhardt
    • 3
  • J. W. G. Janssen
    • 4
  • H. G. Drexler
    • 1
  1. 1.German Collection of Microorganisms & Cell CulturesBraunschweigGermany
  2. 2.Children’s Hospital and Dana-Farber Cancer InstituteBostonUSA
  3. 3.Division of PediatricsJustus Liebig University of GiessenGiessenGermany
  4. 4.Institute of Human GeneticsUniversity of HeidelbergGermany

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