Abstract
BackgroundChildhood pre-B acute lymphoblastic leukemia (ALL) is a bone marrow (BM) derived disease, which often disseminates out of the BM cavity, where malignant cells to a variable degree can be found circulating in the peripheral blood (PB). Normal pre-B cells are absolutely dependent on BM stroma for survival and differentiation. It is not known whether transformed pre-B ALL cells retain any of this dependence, which possibly could impact on drug sensitivity or MRD measurements.ResultsPre-B ALL cells, highly purified by a novel method using surface expression of CD19 and immunoglobulin light chains, from BM and PB show a very high degree of similarity in gene expression patterns, with differential expression of vascular endothelial growth factor (VEGF) as a notable exception. In addition, the cell sorting procedure revealed that in 2 out of five investigated patients, a significant fraction of the malignant cells had matured beyond the pre-B cell stage.ConclusionThe transition of ALL cells from the BM into the circulation does not demand, or result in, major changes of gene expression pattern. This might indicate an independence of BM stroma on the part of transformed pre-B cells, which contrasts with that of their normal counterparts.
Highlights
Childhood pre-B acute lymphoblastic leukemia (ALL) is a bone marrow (BM) derived disease, which often disseminates out of the BM cavity, where malignant cells to a variable degree can be found circulating in the peripheral blood (PB)
In order to establish the relationship between ALL cells in the BM and in the PB, and to resolve how the anatomical location is reflected in the overall gene expression pattern of a pre-B ALL cell, we developed a purification approach based on the presumption that the transformed cells express the lineage marker CD19, but due to the developmental block lack the expression of Immunoglobulin light chain (IgL) protein, normally not expressed until later stages of development [7], on the cell surface
In order to achieve this we used the fact that IgL typically is not rearranged, and not expressed on the cell surface, until the immature B-cell stage [7] (Figure 1A), and since pre-B ALL cells are blocked in their differentiation prior to that stage they would not be expected to display any IgL on the cell surface
Summary
Childhood pre-B acute lymphoblastic leukemia (ALL) is a bone marrow (BM) derived disease, which often disseminates out of the BM cavity, where malignant cells to a variable degree can be found circulating in the peripheral blood (PB). In addition to leading to an uncontrolled cell growth of preB ALL cells, transformation results in a pronounced block of cell differentiation. This developmental disturbance is reflected in the primary anatomical location of the leukemic cells being the bone marrow (BM), which is the primary site for normal progenitor B-lymphocytes. Given the requirement of stroma signalling for normal pre-B cells, it is not obvious that ALL cells residing in the BM are similar to ALL cells in the circulation Malignant cells in these two locations could differ with regard to differentiation stage, cell cycle status or proneness to apoptosis, which might influence drug sensitivity and minimal residual disease (MRD) measurements
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
