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Characterization of ABL1 expression in adult T-cell acute lymphoblastic leukemia by oligonucleotide array analysis

From the Division of Hematology, Department of Cellular Biotechnologies and Hematology, University "La Sapienza", Rome, Italy (SB, ST, EMG, CA, LE, RM, MM, MRR, AV, AG, RF); Hematology and Bone Marrow Transplantation Unit, University of Perugia, Policlinico Monteluce, Perugia, Italy (CMA, CME); Department of Medical Oncology, Dana-Farber Cancer Institute, Boston MA, USA (JR)

Correspondence: Robin Foà, Division of Hematology, University "La Sapienza", Via Benevento 6, 00161 Rome, Italy. E-mail: rfoa{at}bce.uniroma1.it

Background and Objectives: Recent data have highlighted an involvement of ABL1 in T-cell acute lymphoblastic leukemia (T-ALL). Specifically, the presence of a fusion gene involving ABL1 and NUP214, both located at 9q34, has been reported. We sought to evaluate whether TALL patients with overexpression of ABL showed a peculiar gene expression pattern and were characterized by having specific rearrangements.

Design and Methods: We previously assessed the expression profile of 128 adults with ALL by oligonucleotide arrays: 33 had T-ALL. In the current study, we evaluated the expression levels of ABL1 in T-ALL cases and found three patients who had ABL1 levels comparable to those detected in BCR/ABL⁺ cases and one who had a significantly higher level of ABL1 expression. In order to establish the incidence of ABL1 overexpression in TALL, we evaluated 17 additional patients by quantitative (Q)-polymerase chain reaction (PCR) and reverse transcription (RT)-PCR.

Results: The three cases with ABL1 expression levels comparable to those found in BCR/ABL⁺ cases had a specific signature characterized by a high expression of genes involved in regulation of transcription. The fourth case, with the highest levels of ABL1, harbored the NUP214-ABL1 rearrangement, which was confirmed by fluorescence in situ hybridization (FISH). Three of the four patients were refractory to induction chemotherapy. Of the 17 additional patients evaluated by Q-PCR and RT-PCR, none showed ABL1 overexpression.

Interpretation and Conclusions: Overall, overexpression of ABL1 was found in 8% of T-ALL cases. These results underline the value of microarray analyses for the identification of specific signatures associated with ABL1 overexpression, as well as rearrangements, e.g. NUP214-ABL1, in adult T-ALL.

Key words: NUP214, ABL1, T-lineage acute lymphoblastic leukemia, gene expression profile, ABL1 expression.