Expression of JAK/STAT Signaling Proteins at Diagnosis and Remission in Patients with Acute Myeloid Leukemia

Abstract

Objectives: Acute myeloid leukemia (AML), among other malignancies, has been linked to the deregulation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway, which is essential for cell growth, proliferation, and differentiation. This study aimed to investigate the expression of JAK/STAT proteins at diagnosis and remission and how it affects overall survival (OS).

Methods: This is a prospective study conducted in the College of Medicine, Sultan Qaboos University. Using the enzyme-linked immunosorbent assay assay, we estimated the expression levels of JAK/STAT pathway proteins, including pJAK2, pJAK1, JAK1, pSTAT3, pSTAT5, and STAT5, in peripheral blood and bone marrow samples at diagnosis and remission and normalized to the total protein content. Twenty-three adult AML patients (median age = 47) and seven healthy volunteers, who were used as controls, were included in the study. A total of 68 cell lysates were extracted from samples using peripheral blood mononuclear cells isolation assay.

Results: OS was estimated using the Kaplan-Meier curve, and groups were compared with the COX regression model. The overexpression percent was calculated using the chi-square test (p > 0.050). The study revealed that the expression of JAK1, pJAK1, pJAK2, pSTAT3, STAT5, and pSTAT5 in peripheral blood was lower during the diagnosis phase compared to the remission phase (p > 0.050). All these proteins were overexpressed at diagnosis. These proteins did not impact the OS of AML.

Conclusions: The expression levels of these proteins at the time of diagnosis do not significantly influence the OS of patients with AML. The study is limited in sample size and needs to be confirmed in future studies with a larger sample size.

Keywords: Janus Kinases; Leukemia, Myeloid, Acute; STAT Transcription Factors.

Figure 1

Protein expression of (a) JAK1 (b) pJAK1, (c) pJAK2, (d) pSTAT3, (e) STAT5, (f) pSTAT5 in peripheral blood and bone marrow of acute myeloid leukemia at diagnosis and remission.

Figure 2

Overall survival of acute myeloid leukemia patients based on (a) pJAK2 expression levels in peripheral blood, (b) pJAK2 expression levels in bone marrow, (c) pSTAT3 expression levels in peripheral blood, (d) pSTAT3 expression levels in bone marrow, (e) STAT5 expression levels in peripheral blood, (f) STAT5 expression levels in bone marrow, (g) pSTAT5 expression levels in peripheral blood, and (h) OS of AML patients based on pSTAT5 expression levels in bone marrow.