Study of CD123 (interleukin-3 receptor alpha Chain) and nuclear factor kappa B in adult acute myeloid leukemia patients

Abstract

Background: The genomic alterations in acute myeloid leukemia (AML) affect the function of signaling molecules, transcription factors, and growth factor receptors besides they influence the response to treatment. Interleukin-3 receptor alpha chain (CD123) is overexpressed in about 45% of AML, this phenomenon was associated with high blast cell counts at diagnosis, with a worse prognosis. The transcription nuclear factor kappa B (NF-κB) can intervene in oncogenesis through its capacity to regulate the expression of a large number of genes that regulate apoptosis, cell proliferation, and differentiation. This study aimed to assess the relationship between CD123 expression and NF-κB level, in adult patients with AML at presentation and after induction therapy together with a well-known diagnostic and prognostic factors in AML. The study was conducted on forty adult newly diagnosed AML (group A) as well as twenty adult subjects who were hemato-oncologically free, as a control group (group B). Bone marrow (BM) examination and immunophenotyping by flow cytometry (FCM) on BM aspirate, for CD123 and quantitation of NF-κB in BM samples using ELISA (at three levels: Plasma, cytoplasmic and nuclear fraction of blasts, accordingly cytoplasmic/nuclear ratio) were performed for all studied subjects. In addition, levels of CD123 on blast cells and NF-κB were evaluated at D28 for remitted and resistant cases. All patients were positive for CD123 by FCM on BM blasts at time of diagnosis. The median cell counts expressing CD123 was 52.9 (34.4-75.6). Positive expression of CD123 was ≥20%, while in the control subjects CD123 expression was 25.1 (16.9-59.3), with significant decrease in CD123 expression after therapy, Besides, CD123 was also significantly higher in resistant patients compared to remitted patients (P = 0.009). As regard NF-κB, it was significantly higher in AML patients compared to control subjects at the three levels (plasma - cytoplasmic fraction - nuclear fraction) with a significant decrease after therapy. It was found that those NF-κB levels detected at follow-up (D28) on BM expression were significantly higher in resistant patients compared to remitted patients. While only The follow-up results, showed a highly significant positive correlation between CD123 expression on blast cells level and NF-κB plasma level alone (r = 0.587, P = 0.007) while there was not any correlation between CD123 and other two NF-κB levels neither at diagnosis nor at the follow-up. Conclusion: These data suggest that the correlation between CD123 and NF-κB was identified in variable results, and further elucidation of this role is likely to have important implications.

Keywords

• Acute myeloid leukemia
• CD123
• nuclear factor kappa B