Characterization of ABL1 expression in adult T-cell acute lymphoblastic leukemia by oligonucleotide array analysis.
OBJECTIVE
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 T-ALL patients with overexpression of ABL showed a peculiar gene expression pattern and were characterized by having specific rearrangements.


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 T-ALL, 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 ABL, 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.


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.
Chiaretti
Sabina
S
Division of Hematology, Department of Cellular Biotechnologies and Hematology, University La Sapienza, Rome, Italy.
Tavolaro
Simona
S
Ghia
Emanuela Maria
EM
Ariola
Cristina
C
Matteucci
Caterina
C
Elia
Loredana
L
Maggio
Roberta
R
Messina
Monica
M
Ricciardi
Maria Rosaria
MR
Vitale
Antonella
A
Ritz
Jerome
J
Mecucci
Cristina
C
Guarini
Anna
A
Foà
Robin
R
D000293:Adolescent; D000328:Adult; D002868:Chromosomal Proteins, Non-Histone / Q000096:biosynthesis / Q000235:genetics; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000096:biosynthesis / Q000235:genetics; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D016313:Genes, abl; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000097:blood / Q000235:genetics*; D008297:Male; D015337:Multicenter Studies as Topic / Q000706:statistics & numerical data; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D015513:Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D015514:Oncogene Proteins, Fusion / Q000096:biosynthesis* / Q000235:genetics; D000075223:Poly-ADP-Ribose Binding Proteins; D016133:Polymerase Chain Reaction; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D016315:Proto-Oncogene Proteins c-abl / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics
D002868:Chromosomal Proteins, Non-Histone; C084738:DEK protein, human; C501947:EML1-ABL1 fusion protein, human; D018398:Homeodomain Proteins; D047908:Intracellular Signaling Peptides and Proteins; C521114:NUP214-ABL1 fusion protein, human; D009363:Neoplasm Proteins; D015513:Oncogene Proteins; D015514:Oncogene Proteins, Fusion; D000075223:Poly-ADP-Ribose Binding Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C071236:STIL protein, human; C489494:TLX3 protein, human; C071250:TLX1 protein, human; D016044:Fusion Proteins, bcr-abl; D016315:Proto-Oncogene Proteins c-abl