NEWS
2010 - 07 - 13 Publication
One of the major research objectives of the LEHO is to decipher the molecular mechanisms that govern cell death and the cellular resistance to chemotherapy in hematological cancers. A recent publication of the laboratory, entitled "Determination of genes and microRNAs involved in the resistance to fludarabine in vivoin chronic lymphocytic leukemia", sheds new light on the resistance mechanisms that operate in CLL patients treated with fludarabine.
Chronic lymphocytic leukemia (CLL) cells often display genomic aberrations that target key regulatory genes. Although fludarabine is the standard first line therapy to treat CLL, little is known about the mechanisms leading to the resistance of B cells to this purine nucleoside analog in vivo. To address this question, researchers of the LEHO have led a collaborative effort to carry out an analysis of genomic aberrations, gene expression profiles, and microRNAs expression in CLL blood B lymphocytes isolated during the course of patients' treatment with fludarabine. In this paper, they report the identification of genes and miRNAs that may predict clinical resistance of CLL to fludarabine, and describe an interesting oncogenic mechanism in CLL patients resistant to fludarabine by which the complete MYC-specific regulatory network was altered (DNA and RNA levels, and transcriptional targets). These results should prove useful for understanding and overcoming refractoriness to fludarabine and also for predicting the clinical outcome of CLL patients before or early during their treatment.