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

• Published in: Haematologica (Roma) Vol. 92; no. 5; pp. 619 - 626
• Main Authors: Chiaretti, Sabina, Tavolaro, Simona, Ghia, Emanuela Maria, Ariola, Cristina, Matteucci, Caterina, Elia, Loredana, Maggio, Roberta, Messina, Monica, Ricciardi, Maria Rosaria, Vitale, Antonella, Ritz, Jerome, Mecucci, Cristina, Guarini, Anna, Foa, Robin
• Format: Journal Article
• Language: English
• Published: Pavia Haematologica 01.05.2007; Ferrata Storti Foundation
• Subjects: Adolescent; Adult; Biological and medical sciences; Chromosomal Proteins, Non-Histone - biosynthesis; Chromosomal Proteins, Non-Histone - genetics; Clinical Trials as Topic - statistics & numerical data; Female; Fusion Proteins, bcr-abl - biosynthesis; Fusion Proteins, bcr-abl - genetics; Gene Expression Profiling; Gene Expression Regulation, Leukemic; Genes, abl; Hematologic and hematopoietic diseases; Homeodomain Proteins - biosynthesis; Homeodomain Proteins - genetics; Humans; In Situ Hybridization, Fluorescence; Intracellular Signaling Peptides and Proteins - genetics; Leukemia-Lymphoma, Adult T-Cell - blood; Leukemia-Lymphoma, Adult T-Cell - genetics; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Multicenter Studies as Topic - statistics & numerical data; Neoplasm Proteins - biosynthesis; Neoplasm Proteins - genetics; Nucleic Acid Hybridization; Oligonucleotide Array Sequence Analysis; Oncogene Proteins - biosynthesis; Oncogene Proteins - genetics; Oncogene Proteins, Fusion - biosynthesis; Oncogene Proteins, Fusion - genetics; Poly-ADP-Ribose Binding Proteins; Polymerase Chain Reaction; Precursor Cell Lymphoblastic Leukemia-Lymphoma - genetics; Precursor Cell Lymphoblastic Leukemia-Lymphoma - metabolism; Proto-Oncogene Proteins - biosynthesis; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins c-abl - biosynthesis; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; RNA, Neoplasm - biosynthesis; RNA, Neoplasm - genetics; Hematology; NUP214 gene; Acute leukemia; Malignant hemopathy; Abl1 gene; ABL1 expression; Precusor T lymphoblastic leukemia; Lymphoproliferative syndrome; NUP214/ABL1; Oligonucleotide; gene expression profile; Acute lymphocytic leukemia; T-lineage acute lymphoblastic leukemia
• ISSN: 0390-6078; 1592-8721
• DOI: 10.3324/haematol.10865

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.