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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Oncol. | doi: 10.3389/fonc.2018.00555

THE POLYCOMB BMI1 PROTEIN IS CO-EXPRESSED WITH CD26+ IN LEUKEMIC STEM CELLS OF CHRONIC MYELOID LEUKEMIA

 Sara Galimberti1*,  Susanna Grassi1,  Claudia Baratè2, Francesca Guerrini1, Elena Ciabatti1,  Francesca Perutelli1, Federica Ricci1,  Giada Del Genio1,  Marina Montali1, Serena Barachini1, Cecilia Giuliani2, Maria I. Ferreri2,  Elisabetta Abruzzese3,  Chiara Ippolito1,  Alessandra Iurlo4,  Monica Bocchia5,  Anna Sicuranza5, Bruno Martino6,  Lorenzo Iovino1, Gabriele Buda1,  Mario Petrini1,  Antonello Di Paolo1 and  Letizia Mattii1
  • 1Università degli Studi di Pisa, Italy
  • 2Azienda Ospedaliera Universitaria Pisana, Italy
  • 3Azienda Sanitaria Locale Roma 2, Italy
  • 4Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IRCCS), Italy
  • 5Università degli Studi di Siena, Italy
  • 6Mediterranea University of Reggio Calabria, Italy

The Polycomb gene BMI1 expression exerts a negative predictive impact on several hematological malignancies, such as acute and chronic myeloid leukemia (CML), myelofibrosis, and follicular lymphoma. As already demonstrated in CML, BMI1 is responsible for the resistance to the tyrosine kinase inhibitors (TKIs) in a BCR-ABL1-independent way. Even if, it is unknown where BMI1 in CML is expressed (in progenitors or more mature cells).
We decided, therefore, to evaluate if and where the BMI1 protein is located, focusing mainly on the CD34+/CD38-/CD26+ CML progenitors.
To begin we measured, by flow cytometry, the proportion of CD34+/CD26+ cells in 31 bone marrow samples from 20 CML patients, at diagnosis and during treatment with imatinib. After that the bone marrow blood smears were stained with antibodies anti-CD26, BCR-ABL1 and BMI1. These smears were observed by a confocal laser microscope and a 3D reconstruction was then performed.
At diagnosis, CD34+/CD26+ cells median value/μL was 0.48; this number increased from diagnosis to the third month of therapy and then reduced during treatment with imatinib.
The number and behavior of the CD26+ progenitors were independent from the BCR-ABL1 expression, but they summed up what previously observed about the BMI1 expression modulation.
In this work we demonstrate for the first time that in CML the BMI1 protein is co-expressed with BCR-ABL1 only in the cytoplasm of the CD26+ precursors; on the contrary, in other hematological malignancies where BMI1 is commonly expressed (follicular lymphoma, essential thrombocytemia, acute myeloid leukemia), it was not co-localized with CD26 or, obviously, with BCR-ABL1. Once translated into the clinical context, if BMI1 is a marker of stemness, our results would suggest the combination of the BMI1 inhibitors with TKIs as an interesting object of research, and, probably, as a promising way to overcome resistance in CML patients.

Keywords: CML - chronic myelogenous leukemia, polycomb, BMI1, BCR / ABL, CD26 antigen

Received: 13 Jul 2018; Accepted: 08 Nov 2018.

Edited by:

Naval Daver, University of Texas MD Anderson Cancer Center, United States

Reviewed by:

Vikram Mathews, Christian Medical College & Hospital, India
Alice Mims, Comprehensive Cancer Center, The Ohio State University, United States  

Copyright: © 2018 Galimberti, Grassi, Baratè, Guerrini, Ciabatti, Perutelli, Ricci, Del Genio, Montali, Barachini, Giuliani, Ferreri, Abruzzese, Ippolito, Iurlo, Bocchia, Sicuranza, Martino, Iovino, Buda, Petrini, Di Paolo and Mattii. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Sara Galimberti, Università degli Studi di Pisa, Pisa, Italy, sara.galimberti@med.unipi.it