Mutational analysis in BCR-ABL-negative classic myeloproliferative neoplasms

Impact on prognosis and therapeutic choices

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

The diagnostic value of JAK2 mutational analysis in myeloproliferative neoplasms (MPN) is now well established and endorsed by the World Health Organization classification system for hematologic malignancies. The current review is focused on the prognostic impact and therapeutic relevance of JAK2 and other MPN-associated mutations in polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Mutations involving JAK2, MPL, TET2, and ASXL1 are discussed. In general, within a specific disease category, the mere presence or absence of any one of these mutations does not appear to correlate with survival or development of blast phase disease, myelofibrosis, or thrombosis. In contrast, interesting associations between JAK2V617F allele burden and clinical outcome (e.g. lower quartile range allele burden and shorter survival in PMF and higher allele burden and fibrotic transformation in PV) have been made, but require further validation, and their impact on treatment choices is not clear. Similarly, although detection of JAK2V617F status post allogeneic hematopoietic cell transplant indicates minimal residual disease, the general use of mutant allele burden for monitoring treatment response has not been systematically studied. Current information on mutational status and response to JAK2 inhibitor drug therapy is too preliminary to draw any conclusions.

Original languageEnglish (US)
Pages (from-to)576-582
Number of pages7
JournalLeukemia and Lymphoma
Volume51
Issue number4
DOIs
StatePublished - Apr 2010

Fingerprint

Primary Myelofibrosis
Alleles
Polycythemia Vera
Mutation
Neoplasms
Blast Crisis
Essential Thrombocythemia
Residual Neoplasm
Hematologic Neoplasms
Therapeutics
Thrombosis
Transplants
Drug Therapy

Keywords

  • ASXL1
  • JAK2
  • MPL
  • Myelofibrosis
  • Polycythemia
  • TET2
  • Thrombocythemia

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

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title = "Mutational analysis in BCR-ABL-negative classic myeloproliferative neoplasms: Impact on prognosis and therapeutic choices",
abstract = "The diagnostic value of JAK2 mutational analysis in myeloproliferative neoplasms (MPN) is now well established and endorsed by the World Health Organization classification system for hematologic malignancies. The current review is focused on the prognostic impact and therapeutic relevance of JAK2 and other MPN-associated mutations in polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Mutations involving JAK2, MPL, TET2, and ASXL1 are discussed. In general, within a specific disease category, the mere presence or absence of any one of these mutations does not appear to correlate with survival or development of blast phase disease, myelofibrosis, or thrombosis. In contrast, interesting associations between JAK2V617F allele burden and clinical outcome (e.g. lower quartile range allele burden and shorter survival in PMF and higher allele burden and fibrotic transformation in PV) have been made, but require further validation, and their impact on treatment choices is not clear. Similarly, although detection of JAK2V617F status post allogeneic hematopoietic cell transplant indicates minimal residual disease, the general use of mutant allele burden for monitoring treatment response has not been systematically studied. Current information on mutational status and response to JAK2 inhibitor drug therapy is too preliminary to draw any conclusions.",
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AB - The diagnostic value of JAK2 mutational analysis in myeloproliferative neoplasms (MPN) is now well established and endorsed by the World Health Organization classification system for hematologic malignancies. The current review is focused on the prognostic impact and therapeutic relevance of JAK2 and other MPN-associated mutations in polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Mutations involving JAK2, MPL, TET2, and ASXL1 are discussed. In general, within a specific disease category, the mere presence or absence of any one of these mutations does not appear to correlate with survival or development of blast phase disease, myelofibrosis, or thrombosis. In contrast, interesting associations between JAK2V617F allele burden and clinical outcome (e.g. lower quartile range allele burden and shorter survival in PMF and higher allele burden and fibrotic transformation in PV) have been made, but require further validation, and their impact on treatment choices is not clear. Similarly, although detection of JAK2V617F status post allogeneic hematopoietic cell transplant indicates minimal residual disease, the general use of mutant allele burden for monitoring treatment response has not been systematically studied. Current information on mutational status and response to JAK2 inhibitor drug therapy is too preliminary to draw any conclusions.

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