Research article

Fanconi anemia genes are highly expressed in primitive CD34⁺ hematopoietic cells

Michel Aubé^1,2 , Matthieu Lafrance^1,2 , Isabelle Brodeur^1,2 , Marie-Chantal Delisle^1,2 and Madeleine Carreau^1,2

¹  Unité de génétique humaine et moléculaire, CHUQ-Hôpital St-François d'Assise, 10 rue de l'Espinay, Québec, Qc, Canada G1L 3L5

²  Department of Pediatrics, Laval University, Québec, QC, Canada G1L 3L5

author email corresponding author email

BMC Blood Disorders 2003, 3:1doi:10.1186/1471-2326-3-1

Published:	16 June 2003

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.