Vidal Valérie, Robert Guillaume, Goursaud Laure, Durand Laetitia, Ginet Clemence, Karsenti Jean Michel, Luciano Frederic, Gastaud Lauris, Garnier Georges, Braun Thorsten, Hirsch Pierre, Raffoux Emmanuel, Nloga Anne Marie, Padua Rose Ann, Dombret Hervé, Rohrlich Pierre, Ades Lionel, Chomienne Christine, Auberger Patrick, Fenaux Pierre, Cluzeau Thomas
INSERM U1131, Institut Universitaire d'hématologie, Paris, France.
INSERM U1065, Centre Méditerranéen de Médecine Moléculaire, Nice, France.
Oncotarget. 2017 Jul 18;8(29):47103-47109. doi: 10.18632/oncotarget.17482.
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.
阿扎胞苷（AZA）是大多数高危骨髓增生异常综合征（MDS）患者的参考治疗药物，对于不符合强化化疗条件的老年急性髓系白血病（AML）患者，它也能改善总生存期（OS），但缺乏预测接受AZA治疗患者的反应和总生存期的可靠生物学标志物。在一项初步研究中，我们发现bcl-2家族的抗凋亡成员BCL2L10的百分比增加与AZA耐药相关。在本研究中，我们在AZA治疗前，通过流式细胞术前瞻性评估了70例患者（42例MDS和28例AML）中BCL2L10阳性骨髓单个核细胞的预后价值。在基线骨髓原始细胞低于30%的患者中，骨髓BCL2L10阳性细胞的基线百分比与对AZA的反应和总生存期呈负相关，且独立于国际预后评分系统（IPSS）和IPSS修订版（IPSS-R）。具体而言，BCL2L10阳性细胞超过10%的患者总生存期显著更低（阳性率低于10%的患者中位生存期为22.9个月，而阳性率超过10%的患者中位生存期为8.3个月，p = 0.001）。总之，骨髓BCL2L10阳性细胞可能是阿扎胞苷反应和总生存期的生物标志物，对临床实践可能有影响。
