Up-regulation of BAALC gene may be an important alteration in AML-M2 patients with t(8;21) translocation

chromosomal abnormalities detected in human acute myeloid leukaemia subtype 2 (M2). However, AML1-ETO alone is insufficient to develop leukaemia [1, 2]. To search for putative novel leukaemia associated genes, we therefore studied the gene expression profiles in AML-M2. BAALC as one of the genes found may be crucial in the pathogenesis of AML-M2. Some studies have reported that overexpression of BAALC gene was seen in patients with AML and ALL, and more strikingly, in a subset of AML with normal karyotype while predicting a poor prognosis [3–9]. However, its importance in AML-M2 patients with t (8; 21) translo-cation had never been mentioned. To explore the function of BAALC and its possible role in the pathogenesis of human myeloid leukaemia subtype 2(M2) in a hope of finding one more useful biomarker for molecular diagnosis , we have examined the expression level of BAALC in bone marrow mononuclear cells (MNCs) of patients with M2 by using quantitative real-time RT-PCR. Compared to 15 samples of normal bone marrow cells, the expression level of BAALC was significantly up-regulated in 18 pretreated M2 patients. The median level of BAALC transcripts in pretreated patients with AML-M2 and non-malignant blood diseases were 3.93 (ranging 0.71–8.94) and 0.04 (ranging 0.01–0.14), respectively (Fig. 1). The abundance of BAALC mRNA relative to that of ABL mRNA in the cells from most M2 patients was significantly greater than that in the MNCs from non-malignant blood diseases (P < 0.001) (Fig. 1, Table 3). Results from 61 samples of M2 patients at different stages showed that the expression pattern of BAALC was generally parallel to that of AML1-ETO fusion gene in AML-M2 patients with t(8;21) translocation. To evaluate the impact of BAALC expression values on clinical outcome without seeking an optimal cut point, the expanded cohort of AML patients were dichotomized at the median value and divided into two expression groups. In high BAALC group, samples appeared to synthesize more copies of AML-ETO transcript (n ϭ 21; median expression ϭ 9.66, range 0.5–27.5), compared with low BAALC group (n ϭ 40; median expression ϭ 0.45, range 0–12.1). The percentage of myeloid blast cells in bone marrow cells in high BAALC group was markedly higher than that in low BAALC group, namely 53.2% (n ϭ 12) versus 7% (n ϭ 26). In addition, the serum levels of lactic dehydrogenase (LDH) were also significantly different between these two groups. High level of LDH was …