Interactions in the bone marrow (BM) between haematopoietic progenitor cells (HPC) and the BM micro environment are important for the regulation of cell adhesion, proliferation, differentiation and survival. Expression of both CD62L (L-selectin) and CD54 (ICAM-1) on HPC demonstrated to play a role in signal transduction routes for proliferation and growth regulation. Especially CD54 is involved in uncontrolled proliferation and block of apoptosis. Previously, it was described that decreased expression of CD62L in acute myeloid leukemia (AML) was associated with a poor cytogenetic risk profile and an adverse clinical outcome (Graf M et al, Eur J Haematol 2003) Myelodysplastic syndromes are a group of clonal HPC disorders characterized by ineffective hematopoiesis and a propensity to evolve into AML. The International Prognostic Scoring System (IPSS) provides information on both survival and risk of development of an AML. The purpose of our study was to evaluate CD62L and CD54 expression on CD34+ cells in MDS patients by flow cytometry and to assess the value of a CD62L/CD54 ratio for prognostication. Bone marrow samples of 30 newly diagnosed MDS patients (3 RA(RS)/18 RCMD(RS), the <5% blasts group; 5 RAEB-1, 4 RAEB-2, the >5% blasts group), 16 AML patients with prior MDS and 26 healthy volunteers were analyzed for CD62L and CD54 expression on CD34+ cells by using flow cytometry. An adhesion index was calculated as a ratio of the percentage and MFI of CD62L and CD54 positive cells (as was reported by Buccisano et al, Eur J Haematol 2007). The CD62L/CD54 ratio was significantly decreased in MDS with <5% blasts (median 79.09 p<0.0001) as compared to healthy volunteers (median 480.4) and even more decreased in high risk MDS (median 14.67 p<0.0001 and p=0.001 as compared to healthy volunteers and MDS with <5% blasts, respectively) and AML with prior MDS (median 12.54, p<0.0001 and p=0.009 as compared to healthy volunteers and MDS with <5% blasts, respectively). The MDS patients were assigned to the good, intermediate or poor IPSS cytogenetic risk category. Cytogenetics was available for 22 MDS patients. The CD62L/CD54 ratio was significantly lower in the cytogenetic poor risk category compared with the good risk category (median 5.4 and median 70.79 respectively, p=0.018). Moreover, a low CD62L/CD54 ratio correlated significantly with poor cytogenetics, p=0.006. In the group of MDS patients with <5% blasts, 4 developed a refractory anemia with excess of blasts or AML within a follow up period of 12 months. There was a trend for a lower CD62L/CD54 ratio for MDS patients who developed an AML compared with patients who did not. In conclusion, the CD62L/CD54 ratio is significantly decreased in MDS compared with healthy volunteers and even more decreased in AML with prior MDS. Both CD62L and CD54 are involved in regulation of proliferation and apoptosis of the HPC. A decreased adhesion ratio in low risk MDS patients might reflect HPC damage at an early stage of the disease with an increased proliferative capacity and a decreased apoptotic profile. Interestingly, a low CD62L/CD54 ratio showed a significant inverse correlation with the IPSS cytogenetic risk category. Due to an absence of metaphases in a proportion of MDS patients, cytogenetics is not always available. The CD62L/CD54 ratio might serve as a surrogate marker for poor prognosis cytogenetics in case no karyotype is available. Low risk MDS patients who developed an AML within 12 months tended to have a lower CD62L/CD54 ratio. Although these results are promising, sample size and follow up period needs to be extended. The CD62L/CD54 ratio might add to prognostication of MDS patients and might identify MDS patients with <5% blasts who are at risk for development of an AML.
Ossenkoppele:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding. Van de Loosdrecht:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding.
Asterisk with author names denotes non-ASH members.