Expression of CD271 in Normal and Malignant Hematopoietic Progenitor and Stem Cells.

Abstract

The relationship between mesenchymal (MSC) and hematopoietic stem cells (HSC) involves close interaction in the marrow microenvironment. They also may share certain phenotypic features and even possibly a multipotent common precursor. CD271 (also known as LNGFR, p75NTR) has been reported to be a suitable marker of resting primitive MSCs. CD271 and its ligands, neurotrophins (NTs, e.g. nerve growth factor) also play important roles in hematopoiesis, such as enhancement of colony formation by human bone marrow progenitor cells. Dysregulated expression or mutations of NT receptors were associated with the initiation and progression of various malignancies. Based on expression of CD271 in the mesenchymal stem cell compartment, we have hypothesized that this antigen may also be present on a specific subset of normal or malignant hematopoietic progenitor and stem cells. First, we investigated the expression and function of CD271 in normal bone marrow. In controls (n=11), expression of surface CD271 was present on 1.67 ± 1.26% and 2.78 ± 4.50% of CD45+ and CD45− cell populations, respectively. Within the immature hematopoietic compartment, CD271 was expressed on 2.16 ± 1.16% cells defined by CD45 and CD34 expression. When the properties of CD271-expressing CD34 cells were studied in methylcellulose colony assays, those sorted for CD271 antigen showed a much lower clonogenic potential as compared to the CD271-CD34+ cell fractions (10.5 ± 2.12 vs. 183.5 ± 17.68). Subsequently, we investigated whether leukemic cell lines express CD271. We have analyzed HL60, U937, UT7, KG1, K562, HEL, MKN95, NB4 and Kasumi cells using flow cytometry. CD271 was found to be strongly expressed (72.8%) on KG1 AML. Smaller but clearly distinct subpopulations of HEL cells (7.8%) and NB4 cells (5.2%, APL cells) expressed CD271 suggesting either aberrant differentiation in some subpopulations of these cells or the presence of an early precursor population. We then assessed whether CD271 is expressed by CD34+ blasts in patients with myelodysplastic syndrome (MDS n=9) and AML (n=9). CD271 antigen was found on blast cells in 5/9 MDS (1 CMML, 1 RARS, 2 MDS-derived sAML, 1 RA) patients (7.16 ± 1.97% of CD271+ cells within blasts) and 3/9 AML patients (9.70 ± 3.65% of CD271+ cells within blast gate) suggesting that this fraction may differ functionally from the remaining majority of blasts. This is the first report that relates CD271 expression to MDS. The properties of a distinct CD34+ cell population expressing CD271 in myeloid malignancies are currently under investigation. Results of these studies may point towards the presence of a specific subset of precursor/stem cells with clinical and prognostic implications.