JAK3 pathway is constitutively active in B-lineage acute lymphoblastic leukemia.
In this article, we report that primary leukemic B-cell precursors from B-lineage acute lymphoblastic leukemia (ALL) patients overexpress multiple JAK3-activating cytokines as well as their receptors. We also show that amplified expression of JAK3 pathway genes in B-lineage ALL is associated with steroid resistance and relapse. Our findings further demonstrate that several different diagnostic classes of B-lineage lymphoid malignancies exhibit upregulated expression of JAK3 pathway genes, which are associated with an overexpression of genes for JAK3-stimulatory cytokines with concomitant deficiency of JAK3-inhibitory signaling molecules. Thus, despite the rare occurrence of activating JAK3 mutations, JAK3 appears to be constitutively active and represents a viable molecular target in the treatment of a broad range of B-lineage lymphoid malignancies, including B-lineage ALL.
Division of Hematology-Oncology, Department of Pediatrics, Children's Center for Cancer and Blood Diseases, University of Southern California, Keck School of Medicine, Los Angeles, CA 90027-0367, USA. fmuckun@chla.usc.edu
Fatih M
FM
Uckun
Jason
J
Pitt
Sanjive
S
Qazi
D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D006801:Humans; D053616:Janus Kinase 3 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D058990:Molecular Targeted Therapy / Q000379:methods; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018121:Receptors, Cytokine / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
D016207:Cytokines; D018121:Receptors, Cytokine; C507933:JAK3 protein, human; D053616:Janus Kinase 3