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.
Highlights
Azacitidine (AZA) is the reference treatment for most higher-risk myelodysplastic syndromes (MDS) patients [1] which improves overall survival (OS) in elderly acute myeloid leukemia (AML) patients ineligible for intensive chemotherapy (IC) [2]
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 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 IPSSrevised (IPSS-R)
Summary
Azacitidine (AZA) is the reference treatment for most higher-risk myelodysplastic syndromes (MDS) patients [1] which improves overall survival (OS) in elderly acute myeloid leukemia (AML) patients ineligible for intensive chemotherapy (IC) [2]. The French Prognostic Scoring System (FPSS) is based on ECOG, presence of circulating blasts, red blood cell transfusion dependence and cytogenetic risk group. These scores can predict response and OS to AZA treatment [3,4,5,6]. Several genomic alterations detected by single nucleotide polymorphism (SNP) array and methylation profiles-such as TET2 mutations-have been reported to predict better response to hypomethylating agents (HMA) Most of those results were not reproducible, did not allow to predict survival or were hardly applicable in routine practice [7,8,9,10,11]. An exception is the consistently poor prognosis associated with TP53 mutation, but this mutation is largely correlated with the presence of a complex karyotype [12]
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