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Unfolding the Role of Calreticulin in Myeloproliferative Neoplasm Pathogenesis

Tiffany R Merlinsky1,2, Ross L Levine3,2,4,5, Elodie Pronier1,2

  • 1Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|January 19, 2019
PubMed

Insights

Gain-of-function mutations in the Calreticulin (CALR) gene drive myeloproliferative neoplasms (MPNs) by activating the MPL-JAK-STAT pathway. This review explores CALR

Area of Science:

  • Oncology
  • Hematology
  • Molecular Biology

Background:

  • Calreticulin (CALR) is an endoplasmic reticulum (ER) chaperone protein.
  • CALR mutations were discovered in 2013 in myeloproliferative neoplasms (MPNs).
  • These mutations were found in patients negative for JAK2 and MPL mutations.

Purpose of the Study:

  • To review the role of CALR mutations in MPN pathogenesis.
  • To discuss how CALR mutations activate signaling pathways.
  • To explore potential therapeutic strategies targeting CALR mutations.

Main Methods:

  • Review of existing literature on CALR mutations in MPNs.
  • Analysis of the molecular mechanisms of CALR-driven oncogenesis.
  • Discussion of therapeutic implications.

Main Results:

  • Mutated CALR drives MPN development through constitutive activation of the MPL-JAK-STAT signaling axis.
  • CALR mutations represent a key oncogenic driver in a subset of MPN patients.
  • CALR was not previously associated with cancer or hematologic disorders.

Conclusions:

  • CALR mutations are critical in MPN pathogenesis.
  • Understanding CALR's role opens avenues for novel therapeutic approaches.
  • Targeting the MPL-JAK-STAT pathway affected by CALR mutations is a promising strategy.

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