Colony-Forming Cell Assay Detecting the Co-Expression of JAK2V617F and BCR-ABL1 in the Same Clone: A Case Report

Acta Haematol. 2019;141(4):261-267. doi: 10.1159/000496821. Epub 2019 Apr 9.

Abstract

BCR-ABL1-negative myeloproliferative disorders and chronic myeloid leukaemia are haematologic malignancies characterised by single and mutually exclusive genetic alterations. Nevertheless, several patients co-expressing the JAK2V617F mutation and the BCR-ABL1 transcript have been described in the literature. We report the case of a 61-year-old male who presented with an essential thrombocythaemia phenotype and had a subsequent diagnosis of chronic phase chronic myeloid leukaemia. Colony-forming assays demonstrated the coexistence of 2 different haematopoietic clones: one was positive for the JAK2V617F mutation and the other co-expressed both JAK2V617F and the BCR-ABL1 fusion gene. No colonies displayed the BCR-ABL1 transcript alone. These findings indicate that the JAK2V617F mutation was the founding genetic alteration of the disease, followed by the acquisition of the BCR-ABL1 chimeric oncogene. Our data support the hypothesis that a heterozygous JAK2V617F clone may have favoured the bi-clonal nature of this myeloproliferative disorder, generating clones harbouring a second transforming genetic event.

Keywords: BCR-ABL1; Chronic myeloid leukaemia; Essential thrombocythaemia; JAK2V617F.

Publication types

  • Case Reports

MeSH terms

  • Amino Acid Substitution
  • Colony-Forming Units Assay
  • Fusion Proteins, bcr-abl* / biosynthesis
  • Fusion Proteins, bcr-abl* / genetics
  • Gene Expression Regulation, Enzymologic*
  • Gene Expression Regulation, Leukemic*
  • Humans
  • Janus Kinase 2* / biosynthesis
  • Janus Kinase 2* / genetics
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / enzymology
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / genetics
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / pathology
  • Male
  • Middle Aged
  • Mutation, Missense*
  • Thrombocythemia, Essential* / enzymology
  • Thrombocythemia, Essential* / genetics
  • Thrombocythemia, Essential* / pathology

Substances

  • BCR-ABL1 fusion protein, human
  • Fusion Proteins, bcr-abl
  • Jak2 protein, mouse
  • Janus Kinase 2