Tumor-specific HSP90 inhibition as a therapeutic approach in JAK-mutant acute lymphoblastic leukemias Academic Article uri icon

Overview

MeSH Major

  • Benzodioxoles
  • HSP90 Heat-Shock Proteins
  • Janus Kinase 1
  • Janus Kinase 2
  • Neoplasm Proteins
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Purines

abstract

  • The development of the dual Janus kinase 1/2 (JAK1/2) inhibitor ruxolitinib for the treatment of myeloproliferative neoplasms (MPNs) has led to studies of ruxolitinib in other clinical contexts, including JAK-mutated acute lymphoblastic leukemia (ALL). However, the limited ability of JAK inhibition to induce molecular or clinicopathological responses in MPNs suggests a need for development of better therapies for JAK kinase-dependent malignancies. Here, we demonstrate that heat shock protein 90 (HSP90) inhibition using a purine-scaffold HSP90 inhibitor in early clinical development is an effective therapeutic approach in JAK-dependent ALL and can overcome persistence to JAK-inhibitor therapy in ALL cells.

publication date

  • November 26, 2015

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4661170

Digital Object Identifier (DOI)

  • 10.1182/blood-2015-03-635821

PubMed ID

  • 26443624

Additional Document Info

start page

  • 2479

end page

  • 83

volume

  • 126

number

  • 22