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.