Successful Preservation of Native BCR::ABL1 in Chronic Myeloid Leukemia Primary Leukocytes Reveals a Reduced Kinase Activity

Christian Boni, Massimiliano Bonifacio, Marzia Vezzalini, Luigi Scaffidi, Luisa Tomasello, Laurie L. Parker, Diego Boscarino, Dino Paladin, Mauro Krampera, Claudio Sorio

Research output: Contribution to journalArticlepeer-review


Chronic myeloid leukemia (CML) is a myeloproliferative disease caused by the acquisition of t(9;22) generating the fusion tyrosine kinase BCR::ABL1. However, despite the crucial role of this protein in the dysregulation of numerous signal transduction pathways, a direct measure of BCR::ABL1 kinase activity in chronic phase (CP) CML was never accomplished due to intense degradative activity present in mature leukocytes. Therefore, we developed a procedure suitable to preserve BCR::ABL1 protein under non-denaturing, neutral pH conditions in primary, chronic phase (CP)-CML samples. As a result, specific kinase activity was detected utilizing a biotinylated peptide substrate highly selective for c-ABL1. Furthermore, through this approach, BCR::ABL1 kinase activity was barely detectable in CP-CML compared to Ph+ acute lymphoblastic leukemia primary samples, where kinase activity is comparable to those measured in Ph+ cell lines. These in vitro findings provide the first direct measure of BCR::ABL1 kinase activity in primary CP-CML and reveal the presence of a still uncharacterized inhibitory mechanism that maintains BCR::ABL1 in a low activity state in CP-CML despite its overexpression.

Original languageEnglish (US)
Article number904510
JournalFrontiers in Oncology
StatePublished - Jun 8 2022

Bibliographical note

Funding Information:
Funding were provided by University of Verona-Joint Project 2016-2017 and by a research grant from AB Analitica, Padova, Italy.

Publisher Copyright:
Copyright © 2022 Boni, Bonifacio, Vezzalini, Scaffidi, Tomasello, Parker, Boscarino, Paladin, Krampera and Sorio.


  • Bcr Abl
  • acute lymphocytic leukemia
  • chronic myelogenous leukemia
  • imatinib (Gleevec)
  • kinase activity
  • kinase assay
  • philadelphia chromosome
  • tyrosine kinase

PubMed: MeSH publication types

  • Journal Article


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