Oncotarget

Research Papers:

BCL2L10 positive cells in bone marrow are an independent prognostic factor of azacitidine outcome in myelodysplastic syndrome and acute myeloid leukemia

Valérie Vidal, Guillaume Robert, Laure Goursaud, Laetitia Durand, Clemence Ginet, Jean Michel Karsenti, Frederic Luciano, Lauris Gastaud, Georges Garnier, Thorsten Braun, Pierre Hirsch, Emmanuel Raffoux, Anne Marie Nloga, Rose Ann Padua, Hervé Dombret, Pierre Rohrlich, Lionel Ades, Christine Chomienne, Patrick Auberger, Pierre Fenaux and Thomas Cluzeau _

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Oncotarget. 2017; 8:47103-47109. https://doi.org/10.18632/oncotarget.17482

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Abstract

Valérie Vidal1, Guillaume Robert2, Laure Goursaud1, Laetitia Durand1, Clemence Ginet2, Jean Michel Karsenti3, Frederic Luciano2, Lauris Gastaud4, Georges Garnier5, Thorsten Braun6, Pierre Hirsch7,8, Emmanuel Raffoux9, Anne Marie Nloga10, Rose Ann Padua1, Hervé Dombret9, Pierre Rohrlich3, Lionel Ades1,10, Christine Chomienne1, Patrick Auberger2,3, Pierre Fenaux1,10 and Thomas Cluzeau1,2,3

1INSERM U1131, Institut Universitaire d’hématologie, Paris, France

2INSERM U1065, Centre Méditerranéen de Médecine Moléculaire, Nice, France

3Cote d'azur University, Nice Sophia Antipolis University, CHU of Nice, Nice, France

4Centre Antoine Lacassagne, Service d’oncologie, Nice, France

5CH Princesse Grace, Service de Médecine Interne, Monaco, Monaco

6Hôpital Avicenne, Paris 13 University, APHP, Bobigny, France

7Hôpital Saint Antoine, Service d'Hématologie Clinique et de Thérapie Cellulaire, Paris, France

8Sorbonne Universités, UPMC Univ Paris 6, UMRS 938, CDR Saint-Antoine, Paris, France

9Hôpital Saint Louis, Paris 7 University, Service d’Hématologie Adulte, APHP, Paris, France

10Hôpital Saint Louis, Paris 7 University, Service d’Hématologie Sénior, APHP, Paris, France

Correspondence to:

Thomas Cluzeau, email: [email protected]

Keywords: MDS, AML, BCL2L10, IPSS, IPSS-R

Received: November 22, 2016     Accepted: April 14, 2017     Published: April 27, 2017

ABSTRACT

Azacitidine (AZA), the reference treatment for most higher-risk myelodysplastic (MDS) patients can also improve overall survival (OS) in elderly acute myeloid leukemia (AML) patients ineligible for intensive chemotherapy, but reliable biological markers predicting response and OS in patients treated with AZA are lacking. In a preliminary study, we found that an increase of the percentage of BCL2L10, an anti-apoptotic member of the bcl-2 family, was correlated with AZA resistance. In this study, we assessed prospectively by flow cytometry the prognostic value of BCL2L10 positive bone marrow mononuclear cells in 70 patients (42 MDS and 28 AML), prior to AZA treatment.

In patients with baseline marrow blasts below 30%, the baseline percentage of bone marrow BCL2L10 positive cells inversely correlated with response to AZA and OS independently of the International Prognostic Scoring System (IPSS) and IPSS-revised (IPSS-R). Specifically, OS was significantly lower in patients with more than 10% BCL2L10 positive cells (median 8.3 vs 22.9 months in patients with less than 10% positivity, p = 0,001). In summary, marrow BCL2L10 positive cells may be a biomarker for azacitidine response and OS, with a potential impact in clinical practice.


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