Decreased L‐selectin expression in CD34‐positive cells from patients with chronic myelocytic leukaemia

Abstract

Abnormal adhesive interaction between bone marrow stroma and progenitors, one of the causes of unregulated proliferation in chronic myelocytic leukaemia (CML), may be caused by some alterations in adhesion molecules on CML progenitors. We investigated the expression of adhesion molecules (CD44, VLA-5, VLA-4, LFA-1, ICAM-1, L-selectin and c-kit) on bone marrow CD34++ cells from 16 CML patients by three-colour flow cytometry. The mean percentage of cells expressing L-selectin in the CD34++CD38+(or)++ fraction from untreated CML patients was significantly lower, and that in the CD34++CD38- fraction tended to be lower than that from normal controls. Among 11 CML patients treated with interferon-alpha (IFN-alpha), the mean percentage of the cells expressing L-selectin in the CD34++CD38- fraction from three patients with a low percentage of Ph1(+) cells in bone marrow was significantly higher than that from five patients with a high percentage of Ph1(+) cells. In addition, L-selectin expression rate was inversely correlated to the percentage of Ph1(+) cells. There was no significant difference between the untreated patients and normal controls with regard to the expression rates of the other adhesion molecules in each CD34++ fraction except LFA-1. These data suggest that decreased L-selectin expression in CML CD34++ cells reflects one of the features of malignant CML progenitors.

BCR/ABL-mediated downregulation of genes implicated in cell adhesion and motility leads to impaired migration toward CCR7 ligands CCL19 and CCL21 in primary BCR/ABL-positive cells

“…[31][32][33][34][35][36][37] Decreased mRNA levels for L-selectin in p210 UCB and early CP CML CD34 þ cells is consistent with published reports demonstrating decreased expression of L-selectin on BM CD34 þ cells derived from CML patients. [38][39][40] We observed populations of CD34 þ cells with higher and lower levels of L-selectin protein expression in primary cells as well as in the UCB transduction model possibly based on subpopulations. Hence, it is possible that the decreased levels of ICAM1 and L-selectin in CML samples is due to skewing of the population away from the population expressing higher numbers of these adhesion molecules.…”

Four-Color Flow Cytometry Identifies Virtually All Cytogenetically Abnormal Bone Marrow Samples in the Workup of Non-CML Myeloproliferative Disorders

“…By comparing patterns of antigen expression on a given cell population with the patterns identified on normal cells of that type, one potentially can identify abnormalities that, if sufficiently great, may substitute for clonality studies in identifying malignancy. A small number of studies during the past decade have reported abnormalities of one or a few myeloid antigens in CML, including decreased CD16, 4-6 decreased CD32, 5 decreased L-selectin expression on CD34+ cells, 7 aberrant expression of CD56 on blasts and myeloid cells, 8,9 and aberrant expression of lymphoid antigens such as CD2, CD5, and CD7 on the blasts in CML blast crisis. 10 Reported flow cytometric abnormalities among the NCMPDs have included the Particularly useful combinations of antibodies were those that identified antigens expressed over a wide range of intensities in the population of interest.…”

Evaluation of the prognostic relevance of l‐selectin and ICAM1 expression in myelodysplastic syndromes

“…All these reports lead to the conclusion that the abnormal expression of antigens is not a mere surface abnormality but is related to the intrinsic process generating myelodysplasia. Moving from these acquisitions, we have considered that, if MDS arises from a progressive genetic damage within the haematopoietic stem cell compartment (12,(30)(31)(32)(33)(34)(35)(36)(37)(38)(39), it is also conceivable that other extrinsic or intrinsic mechanisms may contribute to the biology of disease and progression toward sAML. Ratio >1 Ratio <1 P = 0.002 64% 11% Figure 4 The value of L-selectin ⁄ ICAM1 ratio and the risk of disease progression.…”