Megakaryocytic and Platelet Dysplasia in MDS Patients as Detected by Multiparameter Flow Cytometry Immunophenotyping

Introduction: Multiparameter flow cytometry immunophenotyping (FC) has shown the presence of phenotypic abnormalities in both CD34 precursors and maturing myeloid and erythorid cells in patients with myelodysplastic syndromes (MDS). However, detection of megakaryocytic dysplasia by FC still remains a challenge.

Aims: To evaluate the potential utility of FC analysis of megakaryopoesis and platelet immunophenotype in MDS patients for the diagnosis and prognostic evaluation of the disease.

Methods: A total of 54 peripheral blood (PB) samples corresponding to 39 patients with MDS and 15 controls (6 healthy subjects, 3 reactive cytopenias, 3 patients with May-Heglin syndrome and 3 myeloproliferative disorders) were collected in sodium citrate. In all cases, the median amount of expression of CD31, CD34, CD36, CD41a, CD41b, CD42a, CD42b, CD61, CD62P, CD63, PAC-1 and Fibrinogen receptor was evaluated on circulating platelets as refleted by the median fluorescence intensity (MFI). Morphologic megakaryocytic dysplasia was evaluated in parallel in bone marrow samples from the same MDS individuals.

Results: Morphological megakaryocytic dysplasia was detected in 49% of MDS patients who showed a shorter median overall survival (50 ± 8 vs 107 ± 12 months; p = 0.04). The following FC abnormalities were detected in circulating PB platelets of MDS patients: increased FSC and SSC (36%), overexpression of CD36 (18%), CD31 (36%), CD41b (20%), CD42b (2.5%) and CD61 (20%) and underexpression of CD36 (10%) and CD61 (5%). One case of aberrant CD34 expression was detected. A total of 27 (69.2%) patients presented at least one of these abnormalities by FC. Eighty percent of patients with morphological dysplasia and 64% without showed immunophenotypic abnormalities. According to IPSS, 6 patients constituted a high risk group (HRG) (Int-2 and High) and 28 a low risk group (LRG) (Int-1 and Low). Platelet phenotypic aberrations were detected in 83% of the HRG and in 75% of the LRG. Immunophenotypic abnormalities were not detected in myeloproliferative disorders. All May-Heglin cases and 2 reactive cytopenias presented overexpression of at least one of the following: FSC, SSC, CD31, CD36, CD41a, CD41b, CD42b and CD61. Deficient expression of CD36, CD61 and aberrant expression of CD34 were unique to MDS.

Conclusion: Our results show the presence of immunophenotypic abnormalities in PB platelets from MDS patients, the abnormally decreased reactivity for CD36 and CD61 together with aberrant CD34 expression being of potential diagnostic utility in MDS.