Work

Unfolding the Role of Calreticulin in Myeloproliferative Neoplasm Pathogenesis

Year: 2019

Type: article

Abstract: In 2013, two seminal studies identified gain-of-function mutations in the Calreticulin (CALR) gene in a subset of JAK2/MPL-negative myeloproliferative neoplasm (MPN) patients. CALR is an endoplasmic reticulum (ER) chaperone protein that normally binds misfolded proteins in the ER and prevents their export to the Golgi and had never previously been reported mutated in cancer or to be associated with hematologic disorders. Further investigation determined that mutated CALR is able to achieve oncogenic transformation primarily through constitutive activation of the MPL–JAK–STAT signaling axis. Here we review our current understanding of the role of CALR mutations in MPN pathogenesis and how these insights can lead to innovative therapeutics approaches.

Source: Clinical Cancer Research

DOI: 10.1158/1078-0432.ccr-18-3777

Authors: Tiffany R. Merlinsky, Ross L. Levine, Elodie Pronier

Institution: Memorial Sloan Kettering Cancer Center

Language: English

Topic: Myeloproliferative Neoplasms: Diagnosis and Treatment

Subfield: Genetics

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funder: National Cancer Institute