Deleterious and Oncogenic Mutations in the IL7RA

Author(s)

Campos, Livia Weijenborg ; Pissinato, Leonardo Granato ; Yunes, Jose Andres

• Document type: Journal article
• Source: CANCERS; v. 11, n. 12, p. 18-pg., 2019-12-01.

Abstract

Interleukin 7 (IL-7) is a critical cytokine that plays a fundamental role in B- and T-cell development and in acute lymphoblastic leukemia (ALL). Its receptor (IL7R) is a transmembrane heterodimer formed by the IL7R alpha and the IL2R gamma chain (gamma c). The IL7R signals through the JAK/STAT pathway. Loss-of-function mutations and some polymorphisms of the IL7R alpha were associated to immunodeficiency and inflammatory diseases, respectively. Gain-of-function mutations were described in T-cell ALL and in high risk precursor B-cell ALL. Most confirmed loss-of-function mutations occur in the extracellular part of the IL7R alpha while oncogenic mutations are exclusively found in the extracellular juxtamembrane (EJM) or transmembrane regions. Oncogenic mutations promote either IL7R alpha/IL7R alpha homodimerization and constitutive signaling, or increased affinity to gamma c or IL-7. This work presents a review on IL7R alpha polymorphisms/mutations and attempts to present a classification based on their structural consequences and resulting biological activity. (AU)

• FAPESP's process: 12/12802-1 - Cooperating mutations, functional studies and antibodies against the mutant IL7R in acute lymphoblastic leukemia
• Grantee: José Andrés Yunes
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/20015-5 - Aberrant IL7R signaling in leukemogenesis: from the basics to potential therapeutics
• Grantee: José Andrés Yunes
• Support Opportunities: Regular Research Grants