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, Foà Robin
Division of Hematology, Department of Cellular Biotechnologies and Hematology, University La Sapienza, Rome, Italy.
Haematologica. 2007 May;92(5):619-26. doi: 10.3324/haematol.10865.
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.
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.
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.
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.
近期数据突显了ABL1在T细胞急性淋巴细胞白血病（T-ALL）中的作用。具体而言，已有报道称存在一种涉及均位于9q34的ABL1和NUP214的融合基因。我们试图评估ABL过表达的T-ALL患者是否呈现出独特的基因表达模式以及是否具有特定重排特征。
我们之前通过寡核苷酸阵列评估了128例成人ALL患者的表达谱：其中33例为T-ALL。在本研究中，我们评估了T-ALL病例中ABL1的表达水平，发现3例患者的ABL1水平与在BCR/ABL(+)病例中检测到的水平相当，1例患者的ABL1表达水平显著更高。为确定T-ALL中ABL1过表达的发生率，我们通过定量（Q）-聚合酶链反应（PCR）和逆转录（RT）-PCR评估了另外17例患者。
3例ABL1表达水平与BCR/ABL(+)病例中相当的病例具有特定特征，其特点是参与转录调控的基因高表达。第4例ABL水平最高的病例存在NUP214-ABL1重排，荧光原位杂交（FISH）证实了这一点。4例患者中有3例对诱导化疗耐药。在通过Q-PCR和RT-PCR评估的另外17例患者中，均未显示ABL1过表达。
总体而言，在8%的T-ALL病例中发现了ABL1过表达。这些结果强调了微阵列分析对于识别成人T-ALL中与ABL1过表达以及重排（如NUP214-ABL1）相关的特定特征的价值。
