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Published on: February 21, 2018
Preferential expression of the transcription coactivator HTIF1alpha gene in acute myeloid leukemia and MDS-related
D Gandini1, C De Angeli, G Aguiari
1Centro di Biotecnologie, Sezione di Studi Biochimici, Università degli Studi di Ferrara, Via L. Borsari 46, 44100 Ferrara, Italy.
Abstract:
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.
Insights
HTIF1alpha, a gene linked to acute myeloid leukemias (AML), shows altered RNA expression in leukemic cells. Its expression varies by AML subtype and is high in myeloid cell lines, suggesting a role in myeloid differentiation.
Area of Science:
- Molecular Biology
- Hematology
- Cancer Genetics
Background:
- HTIF1alpha, a transcription coactivator, is encoded by a gene on chromosome 7q32-34, a region critical in acute myeloid leukemias (AML).
- The gene's potential involvement in AML prompted investigation into its DNA structure and RNA expression in leukemic cells.
Purpose of the Study:
- To investigate the DNA structure and RNA expression of HTIF1alpha in leukemic cells from AML patients.
- To determine the correlation between HTIF1alpha expression and AML subtypes, myelodysplastic syndrome (MDS), and myeloid cell differentiation.
Main Methods:
- Analysis of HTIF1alpha DNA structure and RNA expression in leukemic cells from 36 AML patients (28 de novo, 8 secondary to MDS).
- Comparison of HTIF1alpha expression in different AML subtypes (M1-M5), MDS, and normal mononuclear cells.
- Assessment of HTIF1alpha expression in myeloid cell lines (HL60, NB4, K562) during induced differentiation.
Main Results:
- No abnormal HTIF1alpha DNA fragments were found; DNA loss was observed in patients with chromosome 7q32 deletions/translocations.
- HTIF1alpha RNA was detected in acute myelocytic leukemic blasts but was nearly undetectable in normal mononuclear cells.
- HTIF1alpha expression was higher in M1-M3 AML subtypes, low in M4-M5 AML, and significantly overexpressed in MDS-related AML (MDR-AML).
Conclusions:
- HTIF1alpha expression is altered in AML and MDR-AML, suggesting its potential role in leukemogenesis.
- HTIF1alpha expression levels vary across AML subtypes and are distinctly regulated during myeloid differentiation.
- HTIF1alpha may play a significant role in myeloid differentiation processes within hematopoietic lineages.
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