Coexpression of Bmi-1 and Interleukin-3 Receptor Alpha Chain (CD123) Correlate with Poor Prognosis In Acute Myeloid Leukemia
Authors: Dybko Jaroslaw , Urbaniak-Kujda Donata , Kapelko-Slowik Katarzyna , Kuliczkowski Kazimierz 
Published: October 2019

Abstract
Abstract 4324

Introduction
Acute myeloid leukemia (AML) is characterized by the accumulation of immature cells due to disturbed differentiation and proliferation of the myeloid lineage. The traditional AML classification based on morphology, immunophenotyping, and cytogenetic abnormalities is not perfect, in part, because the leukemic population is functionally heterogeneous. AML cells comprise leukemic stem cells (LSCs) and mature leukemia cells that have differentiated abnormally. There has been a recent effort to identify new markers underlying this functional heterogeneity. Bmi-1 is a member of the Polycomb-group (PcG) proteins and is thought to inhibit inhibits cellular senescence and apoptosis. Bmi-1 was also recognized as an essential regulator of the self-renewal capabilities of both hematopoietic stem cells (HSCs) and leukemic stem cells (LSCs). Additional markers of LSCs have been described recently. One of these, interleukin-3 receptor alpha chain (CD123) expressed on AML cells caused higher cycling activity and resistance to apoptosis induced by the lack of growth factor. Coexpression of Bmi-1 and CD123 might be indicative of poor prognosis and might identify patients requiring aggressive therapeutic schedules.

Patients and methods
Cells lines used included two AML lines (HL-60 and KG-1a), one chronic myeloid leukemia in blast crisis (K562), and one pre-B acute lymphoblastic leukemia (SD-1). A cohort of 58 patients newly diagnosed with AML during the previous five years at our center. Patient BM samples were obtained during routine diagnostic procedures before antineoplastic chemotherapy was started. Diagnosis was based on morphology, cytochemistry, and expression of leukocyte differentiation antigens. All patients were characterized by cytogenetics. Flow-cytometry was used to analyze bone marrow samples to identify Bmi-1+CD123+ population.

Results
Patient samples were divided into 2 groups. Patients in FAB subtypes M0 and M1 comprised group A (N = 20), and patients in all other subtypes comprised group B (N = 38). The median percentages of Bmi-1 positive cells and CD123 positive cells were higher in group A than in group B and healthy controls. There were significant differences in Bmi-1 expression between groups A and B (p = 0.002) and between healthy controls and all AML patients (p = 0.0007). There were no significance differences in CD123 expression between groups A and B but the percentage of CD123 positive cells in healthy controls was significantly lower than in all AML patients (p = 0.0001). Among all AML patients Bmi-1 expression and CD123 expression in CD34+ cells were highly correlated (R = 0.76, p = 0.001).

Conclusions
We thought it important to test coexpression of Bmi-1 and CD123 in the CD34 BM population of AML patients as these markers were both prognostic factors in AML. Our results showed that expression of these markers correlated and together provided an important predictor of prognosis in AML. The criteria of AML stratification are commonly known. However, CD123 and Bmi-1 could become “new” prognostic factors in AML as well as targets for therapeutic approaches. The facts that Bmi-1 is localized in the nucleus (Gil, et al 2005) and is expressed in both hematopoietic and leukemic stem cells (Lessard, et al 2003) makes the hypothetical use of Bmi-1-targeted inhibitors more complex. Thus, further investigation to refine prognosis and to optimize therapy of AML based on Bmi-1 expression in combination with other markers is needed.

Disclosures:
No relevant conflicts of interest to declare.