Indication

Target/marker/pathway

Summary

Licensing status

Publication and contact information

Hematology

Myeloproliferative disorder

Calreticulin (CALR)

Genetic studies suggest neutralizing CALR mutations associated with myeloproliferative neoplasms could help treat the disease. Mutations in Janus kinase-2 (JAK-2) and other genes cause the majority of myeloproliferative neoplasms, but genetic causes for about 30%-45% of cases are unknown. In the first study, exome sequencing identified frameshift mutations in CALR that altered the C-terminal peptide in all six patients lacking known mutations. The CALR mutations were confirmed in 67% of patients with thrombocythemia and 88% of patients with myelofibrosis in a validation cohort. In the second study, exome sequencing identified CALR mutations in 70%-84% of samples from 151 patients with myeloproliferative neoplasms that lacked JAK-2 mutations but not in patients with other cancers. In mouse B cells, expression of the most common Calr mutant increased cell proliferation compared with wild-type Calr expression. Next steps include designing mAbs targeting the new C-terminal peptide sequence of mutant CALR. Authors from the first study plan to start a company to develop anti-CALR antibodies.

SciBX 7(3); doi:10.1038/scibx.2014.89
Published online Jan. 23, 2014

For findings in first study, patent application filed for diagnostic applications and for mutant CALR as a therapeutic target; diagnostic applications available for licensing

Patent and licensing status unavailable for findings in second study

Klampfl, T. et al. N. Eng. J. Med.; published online Dec. 10, 2013;
doi:10.1056/NEJMoa1311347
Contact: Robert Kralovics, Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
e-mail:
robert.kralovics@cemm.oeaw.ac.at

Nangalia, J. et al. N. Eng. J. Med.; published online Dec. 10, 2013;
doi:10.1056/NEJMoa1312542
Contact: Anthony R. Green, Cambridge Institute for Medical Research, Cambridge, U.K.
e-mail:
arg1000@cam.ac.uk