Oncotarget

Research Papers:

BCL2L10 is a predictive factor for resistance to Azacitidine in MDS and AML patients

Thomas Cluzeau, Guillaume Robert, Nicolas Mounier, Jean Michel Karsenti, Maeva Dufies, Alexandre Puissant, Arnaud Jacquel, Aline Renneville, Claude Preudhomme, Jill Patrice Cassuto, Sophie Raynaud, Frederic Luciano and Patrick Auberger _

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Oncotarget. 2012; 3:490-501. https://doi.org/10.18632/oncotarget.481

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Abstract

Thomas Cluzeau1-4,*, Guillaume Robert1-3*, Nicolas Mounier4, Jean Michel Karsenti4, Maeva Dufies1-3, Alexandre Puissant1-3, Arnaud Jacquel1-3, Aline Renneville6, Claude Preudhomme6, Jill-Patrice Cassuto4, Sophie Raynaud5, Frederic Luciano1-3 and Patrick Auberger1-4

1 INSERM U1065, Centre Mediterranéen de Médecine Moléculaire, Team «Cell Death, Differentiation, Inflammation and Cancer», Nice, France

2 Université de Nice, France

3 Equipe labellisée par la Ligue Nationale Contre le Cancer (2011-2013), Paris

4 CHU de Nice, Service d’Hématologie Clinique, France

5 CHU de Nice, Laboratoire d’Onco-hématologie, France

6 CHRU de Lille, Centre de Biologie-Pathologie, Laboratoire d’Hématologie, France

* Denotes equal contribution

Received: April 13, 2012, Accepted: April 28, 2012, Published: May 9, 2012

Keywords: MDS, Azacitidine, resistance, BCL2L10, prognosis

Correspondence:

Patrick Auberger,

Abstract

Azacitidine is the leading compound to treat patients suffering myelodysplastic syndrome (MDS) or AML with less than 30% of blasts, but a majority of patients is primary refractory or rapidly relapses under treatment. These patients have a drastically reduced life expectancy as compared to sensitive patients. Therefore identifying predictive factors for AZA resistance is of great interest to propose alternative therapeutic strategies for non-responsive patients. We generated AZA-resistant myeloid cell line (SKM1-R) that exhibited increased expression of BCL2L10 an anti-apoptotic Bcl-2 family member. Importantly, BCL2L10 knockdown sensitized SKM1-R cells to AZA effect suggesting that increased BCL2L10 expression is linked to AZA resistance in SKM1-R. We next established in 77 MDS patients that resistance to AZA is significantly correlated with the percentage of MDS or AML cells expressing BCL2L10. In addition, we showed that the proportion of BCL2L10 positive bone marrow cells can predict overall survival in MDS or AML patients. We propose a convenient assay in which the percentage of BCL2L10 expressing cells as assessed by flow cytometry is predictive of whether or not a patient will become resistant to AZA. Therefore, systematic determination of BCL2L10 expression could be of great interest in newly diagnosed and AZA-treated MDS patients.


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