Development of paroxysmal nocturnal hemoglobinuria in CALR-positive myeloproliferative neoplasm

Yarden S. Fraiman, Nathan Cuka, Denise Batista, Milena V. Vuica-Ross, Alison R. Moliterno

Research output: Contribution to journalArticle

Abstract

Paroxysmal nocturnal hemoglobinuria (PNH), a disease characterized by intravascular hemolysis, thrombosis, and bone marrow failure, is associated with mutations in the PIG-A gene, resulting in a deficiency of glycosylphosphatidylinositol-anchored proteins. Many hypotheses have been posed as to whether PNH and PIG-A mutations result in an intrinsic survival benefit of CD55−/CD59− cells or an extrinsic permissive environment that allows for their clonal expansion within the bone marrow compartment. Recent data have identified the concurrence of PIG-A mutations with additional genetic mutations associated with myeloproliferative disorders, suggesting that some presentations of PNH are the result of a stepwise progression of genetic mutations similar to other myelodysplastic or myeloproliferative syndromes. We report for the first time in the literature the development of clinically significant PNH in a patient with JAK2V617F-negative, CALR-positive essential thrombocythemia, providing further support to the hypothesis that the development of PNH is associated with the accumulation of multiple genetic mutations that create an intrinsic survival benefit for clonal expansion. This case study additionally highlights the utility of genomic testing in diagnosis and the understanding of disease progression in the clinical setting.

Original languageEnglish (US)
Pages (from-to)107-110
Number of pages4
JournalJournal of Blood Medicine
Volume7
DOIs
StatePublished - May 30 2016

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Paroxysmal Hemoglobinuria
Mutation
Neoplasms
Bone Marrow
Essential Thrombocythemia
Myeloproliferative Disorders
Glycosylphosphatidylinositols
Hemolysis
Disease Progression
Thrombosis
Genes
Proteins

Keywords

  • Calreticulin
  • Myelofibrosis
  • PIGA deletion
  • SNP array

ASJC Scopus subject areas

  • Hematology

Cite this

Development of paroxysmal nocturnal hemoglobinuria in CALR-positive myeloproliferative neoplasm. / Fraiman, Yarden S.; Cuka, Nathan; Batista, Denise; Vuica-Ross, Milena V.; Moliterno, Alison R.

In: Journal of Blood Medicine, Vol. 7, 30.05.2016, p. 107-110.

Research output: Contribution to journalArticle

Fraiman, Yarden S.; Cuka, Nathan; Batista, Denise; Vuica-Ross, Milena V.; Moliterno, Alison R. / Development of paroxysmal nocturnal hemoglobinuria in CALR-positive myeloproliferative neoplasm.

In: Journal of Blood Medicine, Vol. 7, 30.05.2016, p. 107-110.

Research output: Contribution to journalArticle

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