Btk and NFκB as prognostic biomarkers and potential therapeutic targets in B cell acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL) is a malignant disorder of lymphoid progenitor cells characterized by diverse cytogenetic and molecular abnormalities. Although chemotherapy can cure a major proportion of ALL patients, some may relapse and develop serious complications including death. Bruton tyrosine kinase (Btk), a cytoplasmic protein mainly expressed in hematopoietic cells, and nuclear factor kappa B (NFκB), a transcription factor that can bind to Btk promoters to induce its transcription. Both Btk and NFκB are involved in lymphoma, multiple myeloma, acute myeloid leukemia, breast cancer, non-small cell lung cancer, thyroid cancer and other tumors. Here we report that Btk and NFκB are widely expressed in bone marrow mononuclear cells of ALL patients and leukemia cell lines. We observed that Btk and NFκB expression were upregulated in newly diagnosed patients’ samples, reduced to lower levels in complete remission patients’ samples, and elevated again upon disease relapse. Furthermore, we found that patients with overexpression of Btk and NFκB have poor prognosis. Our findings show that Btk and NFκB are involved in the pathogenesis, development, progression and prognosis of ALL, and may shed light on targeting therapy for ALL treatment.