Down-modulation of the C/EBPα transcription factor in core binding factor acute myeloid leukemias
D Cilloni, S Carturan, E Gottardi, F Messa, E Messa… - Blood, 2003 - ashpublications.org
D Cilloni, S Carturan, E Gottardi, F Messa, E Messa, M Fava, D Diverio, A Guerrasio…
Blood, 2003•ashpublications.orgAcute myeloid leukemia (AML) is characterized by abnormalities frequently affecting
transcriptional control elements, leading to differentiation block. 1 C/EBP is one of the most
frequently involved transcription factors, being disrupted by point mutations in 7% to 11% of
cases. 2-3 In the setting of the t (8; 21) AML, C/EBP function has been shown to be
downregulated by the AML-ETO fusion protein. 4 The latter mechanism was reported as a
peculiarity of t (8; 21)-positive AML, apparently not shared by other subtypes. 4 Using a …
transcriptional control elements, leading to differentiation block. 1 C/EBP is one of the most
frequently involved transcription factors, being disrupted by point mutations in 7% to 11% of
cases. 2-3 In the setting of the t (8; 21) AML, C/EBP function has been shown to be
downregulated by the AML-ETO fusion protein. 4 The latter mechanism was reported as a
peculiarity of t (8; 21)-positive AML, apparently not shared by other subtypes. 4 Using a …
Acute myeloid leukemia (AML) is characterized by abnormalities frequently affecting transcriptional control elements, leading to differentiation block. 1 C/EBP is one of the most frequently involved transcription factors, being disrupted by point mutations in 7% to 11% of cases. 2-3 In the setting of the t (8; 21) AML, C/EBP function has been shown to be downregulated by the AML-ETO fusion protein. 4 The latter mechanism was reported as a peculiarity of t (8; 21)-positive AML, apparently not shared by other subtypes. 4 Using a quantitative real-time polymerase chain reaction (RQPCR) method, 5, 6 we analyzed the C/EBP expression levels in 144 bone marrows (BMs) from AML patients at diagnosis (French-American-British [FAB] distribution: M0, 15; M1, 19; M2, 38; M3, 22; M4, 37; M5, 9; and M6, 4) and in 32 samples (14 BM and 18 peripheral blood [PB]) from healthy controls. Following karyotypic and molecular analysis, 19 of 38 FAB M2 patients were classified as t (8; 21) positive and 16 of 37 FAB M4 cases as inv (16) positive. C/EBP expression was also tested in serial samples from 18 patients during follow-up (7 characterized by t (8; 21), 5 by inv (16), and 6 by a normal karyotype). As shown in Figure 1A, we detected a significant down-modulation of C/EBP transcript in the samples positive for the presence of the t (8, 21) and inv (16) cytogenetic abnormalities with respect to the other types of AMLs (mean value of C/EBP copies/104 ABL copies: 33 638 vs 77 813, P. 0001), which showed values similar to those found in healthy controls (77 865 and 56 845 C/EBP copies/104 ABL copies in normal BM and PB, respectively). Moreover, the comparison between the C/EBP values obtained in BM samples from patients with AML1/ETO-positive FAB M2 AML compared with AML1/ETO-negative FAB M2 cases demonstrated a highly significant difference (32 523 vs 71 985 C/EBP copies/104 ABL copies, P. 0001). Similar differences were detected by analyzing FAB M4 cases with and without the CBFb/MYH11 fusion (35 644 vs 105 173 C/EBP copies/104 ABL copies, P. 0002). The Western blot assays further confirmed these
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