BCR/ABL preleukemic fusion gene in subpopulations of hematopoietic stem and progenitor cells from human UCB.

L Jakl,J Jakubikova,P Kosik,M Kubes,E Markova,M Holop,M Durdik,K Beresova,I Belyaev,M Skorvaga,L Zastko

doi:10.4149/neo_2019_190925n965

Abstract

The BCR/ABL preleukemic fusion gene (PFG) is one of the most frequent fusion genes in acute lymphoblastic leukemia (ALL) and was also detected in hematopoietic cells from umbilical cord blood (UCB) of healthy newborns. Since hematopoietic stem/progenitor cells (HSPC) are considered to be a critical cellular target for origination of leukemia, we have studied the presence of BCR/ABL PFG in expanded subpopulations of HSPC and differentiated cells from UCB of those healthy newborns, who have previously been tested positive for BCR/ABL by screening of their UCB mononuclear cells using RT-qPCR and FISH methods. We isolated cells from human UCB samples positive for BCR/ABL and negative controls. The isolated cells were sorted into 5 hematopoietic and progenitor cell subpopulations. We analyzed BCR/ABL in sorted and expanded subpopulations of UCB using FISH and RT-qPCR. We found that the number of BCR/ABL positive cells was similar in each studied subpopulation and the same as in differentiated lymphocytes. Our data showed that there is no specific subpopulation of hematopoietic and progenitor stem cells with an increased leukemogenic potential due to the presence of higher copies of BCR/ABL.

Highlights

break cluster region (BCR)/ABL preleukemic fusion gene (PFG) is one of the most frequent fusion genes in acute lymphoblastic leukemia (ALL) and was detected in hematopoietic cells from umbilical cord blood (UCB) of healthy newborns
Since hematopoietic stem/progenitor cells (HSPC) are considered to be a critical cellular target for origination of leukemia, we have studied the presence of BCR/ABL PFG in expanded subpopulations of HSPC and differentiated cells from UCB of those healthy newborns, who have previously been tested positive for BCR/ABL by screening of their UCB mononuclear cells using RTqPCR and FISH methods
We analyzed BCR/ABL in sorted and expanded subpopulations of UCB using FISH and reverse transcription (RT)-qPCR Results: We found that the number of BCR/ABL positive cells was similar in each studied subpopulation and the same as in differentiated lymphocytes

Summary

Introduction

BCR/ABL preleukemic fusion gene (PFG) is one of the most frequent fusion genes in acute lymphoblastic leukemia (ALL) and was detected in hematopoietic cells from umbilical cord blood (UCB) of healthy newborns. PFG may arise predominantly in utero during fetal/embryonic development, producing a persistent, but clinically covert preleukemic clone [1, 3,4,5] These clones were detected in umbilical cord blood (UCB) of newborns, usually at frequencies 100-fold higher incidence of leukemia suggesting relatively late origin and possible elimination of most preleukemic clones further in development [6]. Identification of specific HSPC subpopulation(s) in which the PFG is originated can help refine the target cells for therapy leading to a more specific and more effective therapy of primarily diagnosed and/or relapsed leukemia These aspects are highly significant, especially for PFG-associated leukemias with a poor prognosis, including t(9;22)(q34;q11) reciprocal translocation resulting into the Philadelphia (Ph) chromosome and formation of the BCR/ABL fusion gene. This PFG is one of the most frequent (3-5%) and prognostically important PFG associated with pediatric acute lymphoid leukemia (ALL)

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