title: Fanconi anemia genes are highly expressed in primitive CD34+ hematopoietic cells.
abstract: BACKGROUND: Fanconi anemia (FA) is a complex recessive genetic disease characterized by progressive bone marrow failure (BM) and a predisposition to cancer. We have previously shown using the Fancc mouse model that the progressive BM failure results from a hematopoietic stem cell defect suggesting that function of the FA genes may reside in primitive hematopoietic stem cells. METHODS: Since genes involved in stem cell differentiation and/or maintenance are usually regulated at the transcription level, we used a semiquantitative RT-PCR method to evaluate FA gene transcript levels in purified hematopoietic stem cells. RESULTS: We show that most FA genes are highly expressed in primitive CD34-positive and negative cells compared to lower levels in more differentiated cells. However, in CD34- stem cells the Fancc gene was found to be expressed at low levels while Fancg was undetectable in this population. Furthermore, Fancg expression is significantly decreased in Fancc -/- stem cells as compared to wild-type cells while the cancer susceptibility genes Brca1 and Fancd1/Brac2 are upregulated in Fancc-/- hematopoietic cells. CONCLUSIONS: These results suggest that FA genes are regulated at the mRNA level, that increased Fancc expression in LTS-CD34+ cells correlates with a role at the CD34+ differentiation stage and that lack of Fancc affects the expression of other FA gene, more specifically Fancg and Fancd1/Brca2, through an unknown mechanism.
authors.affiliation: Unité de génétique humaine et moléculaire, CHUQ-Hôpital St-François d'Assise, 10 rue de l'Espinay, Québec, Qc, Canada G1L 3L5. madeleine.carreau@crsfa.ulaval.ca
authors.forename: Michel
authors.initials: M
authors.lastname: Aubé
authors.forename: Matthieu
authors.initials: M
authors.lastname: Lafrance
authors.forename: Isabelle
authors.initials: I
authors.lastname: Brodeur
authors.forename: Marie-Chantal
authors.initials: MC
authors.lastname: Delisle
authors.forename: Madeleine
authors.initials: M
authors.lastname: Carreau