Secondary chronic myeloid leukemia in a patient with CALR and ASXL1-mutated primary myelofibrosis

Int J Hematol. 2022 Sep;116(3):442-445. doi: 10.1007/s12185-022-03331-x. Epub 2022 Apr 16.

Abstract

Development of secondary CML has only been casually described, with few reports attempting to analyze and explain the mechanisms behind this phenomenon. Reported cases vary with regard to presumed pathogenesis and clinical characteristics, but similarities can be observed. This report presents the case of a patient diagnosed with CALR and ASXL1-mutated primary myelofibrosis who developed CML 13 years after the initial diagnosis. In contrast with previously reported cases, this patient did not have JAK2 or ABL1 gene mutations, and also exhibited primary resistance to tyrosine kinase inhibitor (TKI) treatment. Here, we analyze the molecular evolution of CML and describe successful treatment with concomitant therapy including a TKI and JAK inhibitor. This report aims to deepen clinical experience and further broaden knowledge about chronic myeloproliferative neoplasms.

Keywords: ASXL1; BCR–ABL1; CALR; Chronic myeloid leukemia; Primary myelofibrosis.

Publication types

  • Case Reports

MeSH terms

  • Calreticulin / genetics
  • Calreticulin / metabolism
  • Chronic Disease
  • Fusion Proteins, bcr-abl / genetics
  • Humans
  • Janus Kinase 2 / genetics
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / drug therapy
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / genetics
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / pathology
  • Leukemia, Myeloid* / drug therapy
  • Mutation
  • Myeloproliferative Disorders* / genetics
  • Primary Myelofibrosis* / diagnosis
  • Protein Kinase Inhibitors / therapeutic use
  • Repressor Proteins / genetics

Substances

  • ASXL1 protein, human
  • Calreticulin
  • Protein Kinase Inhibitors
  • Repressor Proteins
  • Fusion Proteins, bcr-abl
  • Janus Kinase 2