TEL-AML1 translocations with TEL and CDKN2 inactivation in acute lymphoblastic leukemia cell lines

Abstract

The t(12;21) (p 13; q22) results in the fusion of the TEL gene located on chromosome 12 with the AML1 gene located on the derivative chromosome 21. Because this translocation is difficult to detect using standard cytogenetic techniques, 27 previously karyotyped B-lineage acute lymphoblastic leukemia (ALL) cell lines were evaluated for the presence of the TEL-AML1 fusion using the reverse transcriptase- polymerase chain reaction (RT-PCR), fluorescence in situ hybridization (FISH), and cDNA sequencing. Six cell lines expressed the TEL-AML1 chimeric transcript by RT-PCR and the t(12;21) was confirmed by FISH analysis with probes for TEL, AML1, and chromosome 12. While only one of the 6 cell lines with the t(12;21) lost the der(12)t(12;21)-encoded AML1-TEL fusion transcript, 4 cell lines lacked expression of the nontranslocated allele of TEL and 5 cell lines lacked expression of CDKN2. Moreover, in 2 patients (1 with the TEL-AML1 transcript and 1 without), TEL expression was lost with disease progression; le, TEL was expressed in the initial cell lines (established at diagnosis or first relapse) whereas TEL was not expressed in the cell lines established from these patients in late-stage disease. These data show the coexistence of multiple genetic defects in childhood B-lineage ALL Cell lines with t(12;21) will facilitate the study of TEL-AML1 and AML1-TEL fusion proteins as well as TEL and CDKN2 gene inactivation in leukemia transformation and progression.

Childhood near‐tetraploid acute lymphoblastic leukemia: an EGIL study on 36 cases

“…For this reason, we included in this cohort three cases with simultaneous aberrant near‐diploid and/or pseudodiploid metaphases. These findings indicate that tetraploidization could be one of the steps involved during the multistep developmental process of leukemic clones in NT‐ALL probably associated with a growth advantage (10, 23). The tetraploid clone was even lost or overgrown by a related new pseudodiploid clone at 2nd relapse in one patient supporting further this hypothesis.…”

CDKN2 Gene Deletion as Poor Prognosis Predictor Involved in the Progression of Adult B-Lineage Acute Lymphoblastic Leukemia Patients

“…In our research, there were only a few patients with TEL/AML1 and hypodiploidy and even fewer in CDKN2 deletion carriers. Kim found that ALL cell lines with TEL/AML1 fusion gene and deletion of 9p21 had a strong ability to proliferate compared with the cell lines with TEL/AML1 fusion gene only 28 , and deletion of 9p21 may weakened or even reverse the favorable impact of the TEL/AML1 fusion proliferation.…”

Metabolic Profile Of Leukemia Cells Influences Treatment Efficacy Of L‑Asparaginase

“…(Table S1). The HB11;19 cell line was kindly provided by Dr. Anthony Ford from the Institute of Cancer Research (London, UK), and the UOC-B6 cell line was provided by Dr Ondrej Krejci (Massachusetts General Hospital, Boston) (14). The rest of the cell lines were purchased from German Collection of Microorganisms and Cell Cultures (DSMZ, Braunschweig, Germany;).…”