Preferential expression of the transcription coactivator HTIF1alpha gene in acute myeloid leukemia and MDS-related AML.
HTIF1alpha, a transcription coactivator which is able to mediate RARalpha activity and functionally interact with PML, is encoded by a gene on chromosome 7q32-34, which is a critical region in acute myeloid leukemias (AML). With the assumption that this gene may be related to AML, we investigated the HTIF1alpha DNA structure and RNA expression in leukemic cells from 36 M1-M5 AML patients (28 "de novo" and eight "secondary" to myelodysplastic syndrome (MDS)). Abnormal HTIF1alpha DNA fragments were never found, whereas loss of HTIF1alpha DNA was observed in the patients with chromosome 7q32 deletion and translocation, and in one case without detectable chromosome 7 abnormality. HTIF1alpha RNA was found in acute myelocytic leukemic blasts, and was almost undetectable in normal mononuclear cells. The expression varied among the patients: higher in M1 to M3 subtypes, with the highest values in M1; low levels were constantly observed in M4 and M5 AML. In addition, HTIF1alpha was significantly overexpressed in MDS-related AML (MDR-AML), but not in MDS. We also found that HTIF1alpha expression was high in myeloid cell lines. In myeloblastic HL60 and promyelocytic NB4 cells, induced to differentiate along the monocytic-macrophage pathway by TPA or vitamin D3, HTIF1alpha expression decreased, whereas it was maintained at high levels on induction to granulocytic differentiation by RA or DMSO. In K562 cells, HTIF1alpha RNA levels did not change after hemin-induced erythroid differentiation. These results suggest that HTIF1alpha could play a role in myeloid differentiation, being distinctly regulated in hematopoietic lineages.
Gandini
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Centro di Biotecnologie, Sezione di Studi Biochimici, Università degli Studi di Ferrara, Via L. Borsari 46, 44100 Ferrara, Italy.
De Angeli
C
C
Aguiari
G
G
Manzati
E
E
Lanza
F
F
Pandolfi
P P
PP
Cuneo
A
A
Castoldi
G L
GL
del Senno
L
L
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001773:Blood Cells / Q000473:pathology; D001853:Bone Marrow / Q000473:pathology; D016022:Case-Control Studies; D002454:Cell Differentiation; D002869:Chromosome Aberrations; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D004247:DNA / Q000737:chemistry; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007951:Leukemia, Myeloid / Q000145:classification / Q000209:etiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics* / Q000502:physiology; D020033:Protein Isoforms / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology; D014407:Tumor Cells, Cultured
D009687:Nuclear Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D014157:Transcription Factors; C093517:transcriptional intermediary factor 1; D004247:DNA