General AML

Overexpression of ABCG2 and CD200 is associated with poor outcome in AML patients in the ELN-favorable risk group

On 15th June 2017, in an article published in the European Journal of Haematology, Mario Tiribelli and colleagues from Azienda Sanitaria Universitaria Integrata, Udine, Italy, reported results from their retrospective study which aimed to identify factors that are associated with poor outcomes in Acute Myeloid Leukemia (AML) patients with favorable risk according to the European LeukemiaNet (ELN) classification including patients with Core Binding Factor (CBF) positive or Fms Like Tyrosine Kinase 3 (FLT3) Negative / Nucleophosmin-1 positive (FLT3-/NPM1+) Cytogenetically Normal (CN) AML.

Over expression of ABCG2 (Multidrug Resistance [MDR] protein) and CD200 (transmembrane protein of the immunoglobulin superfamily) has been shown to be associated with poor outcomes in AML patients. However, there is a paucity of studies that have investigated the roles of these factors on the outcomes of patients with CBF+ or FLT3-/NPM1+ CN AML patients, hence the rationale for this study.

Sixty-five adult AML patients (median age = 57 years) with CBF+ (n = 16) or FLT3-/NPM1+ CN who were treated at the Azienda Sanitaria Universitaria Integrata between 2008–2015, were included in this retrospective study.  Bone Marrow (BM) samples from patients were analyzed for their expression of ABCG2 and CD200.

The key results of the study were:
  • ABCG2 and CD200 were expressed in 36 (55%) and 33 (51%) patients respectively
  • 3-year Leukemia Free Survival (LFS) in ABCG2+ and ABCG2- patients; 51% vs 82%, Relapse Risk (RR) = 3.3, P = 0.0038
  • 3-year LFS in CD200+ and CD200- patients; 49% vs 82%, RR = 4.4, P = 0.0014
  • 3-year Overall Survival (OS) in ABCG2+ and ABCG2- patients; 39% vs 71%, RR = 2.6, P = 0.02
  • 3-year OS in CD200+ and CD200- patients; 39% vs 68%, RR = 2.5, P = 0.03

In conclusion, the study found that overexpression of ABCG2 and CD200 in ENL-favorable AML patients had a negative impact on outcome.

The authors suggested that their study could aid in treatment decision and new therapies for patients in this ELN-favourable subgroup if their results can be confirmed in a large prospective clinical study.

Abstract

OBJECTIVE: Overexpression of ABCG2 and CD200 has been independently associated with poor outcome in acute myeloid leukemia (AML). However, no data are available on the role of these two factors in patients with core-binding factor (CBF)-positive or FLT3-negative/NPM1-mutated cytogenetically normal (CN) AML.

METHODS: We analyzed 65 adult AML patients with CBF+ (n=16) or FLT3-/NPM1+ CN (n=49), evaluating clinical and biological factors associated with complete remission attainment, leukemia-free survival (LFS) and overall survival (OS).

RESULTS: ABCG2 was expressed in 36 (55%) cases, and CD200 was positive in 33 (51%) cases, six at high levels. Both ABCG2 and CD200 positivity have a negative impact on relapse risk: 3-year LFS was 51% vs 82% in ABCG2+ cases (RR 3.3), 49% vs 82% in CD200+ patients (RR=4.4), and 25% in CD200- high cases (RR=17.1). ABCG2 and CD200 affected also OS with 3-year OS of 39% in ABCG2+ (compared to 71% in ABCG2-; RR=2.6) and CD200+ (compared to 68% in CD200-; RR=2.5) patients.

CONCLUSIONS: Our data confirm a negative impact of ABCG2 and CD200 overexpression also in AML patients considered at favorable risk according to ELN cytogenetic/molecular classification.

References
  1. Tiribelli M. et al. ABCG2 and CD200 define patients at high risk of relapse in ELN favorable subgroup of AML. Eur J Haematol. 2017 Jun 15. DOI: 10.1111/ejh.12915. [Epub ahead of print].