The relationship of cytometric abnormalities and cytogenetic aberrancies in patients with myelodysplastic syndromes

Summary

Diagnosis of myelodysplastic syndromes (MDS) could be a challenge, especially in the absence of obvious morphological features of MDS such as excess of blasts and ring sideroblasts (≥15%). Therefore, it is recommended to carry out cytogenetic, histological and multicolor flow cytometric (MFC) studies of bone marrow (BM). However, there is not enough data on the relationship of cytogenetic aberrations (CGA) and cytometric abnormalities. Our aim was to evaluate sensitivity and specificity of MFC in the MDS without excess of blasts and ring sideroblasts and to study the MFC abnormalities depending on the CGA.

Patients and methods

The study included 41 MDS patients (M/F ratio of 1:1.9; median age, 62 years): 8 MDS cases with 5q-, 4 – MDS with single lineage dysplasia; 29 had MDS with multilineage dysplasia. Of these, there were 19 patients without CGA; 8, with isolated del(5q); 7, with recurrent typical abnormalities (-7/del (7q), del(13q) , t(1; 3), or del(5q) in complex karyotype), and 7 showed non-specific aberrancies (-Y, t (2; 3), del (20q), +8). The control group included 83 patients with cytopenia (aplastic anemias, PNH, iron-deficient anemias, immune thrombocytopenias etc.). MFC examination of BM was performed according to European Leukemia Net recommendations on BD FACSCanto II. The reference values were obtained from BM data of 35 healthy donors. The final conclusion was made in accordance with the integrated flow cytometric scale (iFCS), i.e.: A, no signs of MDS; B, some signs of MDS; C, corresponds to MDS.

Results

The frequencies of B and C were higher in all MDS compared with control group, but there were no significant differences depending on CGA (Fig. 1). The sensitivity and specificity of MFC were 73.2% and 86.7%, respectively. In compartment of early precursors proportions of CD34+ and CD117+ myeloid cells were higher in MDS with typical CGA than in control group. The normal proportion of CD34+ B-cell precursors was preserved in MDS without CGA and with non-specific chromosomal aberrancies. The proportion of CD7+CD34+ was higher in MDS with typical CGA and in MDS with 5q- compared to controls, and in MDS with 5q- compared to MDS without CGA.

Figure 1. Distribution of “ABC” scores according to an integrated flow cytometry scale

The smallest proportion of granulocytes was observed in MDS with typical GCA. The lower granularity index and increased proportion of CD10+ granulocytes, were more typical for MDS with 5q-. Abnormal maturation patterns and high expression of CD56 in granulocytes were more intrinsic for MDS with typical GCA (Table 1). There were no differences in the monocytes.

Conclusion

Even with MDS free of obvious morphological signs of MDS, MFC retains a fairly high sensitivity, regardless of CGA. MDS with 5q- was characterized by a low number of CD34+ B-cell precursors, a high proportion of CD7+ and CD117+ cells and a low granularity index. MDS with typical CGA was characterized by high proportion of CD34+ and CD117+ cells, a low proportion of granulocytes with pronounced abnormal cytometric abnormalities. This indicates that there is probably a relationship between the CGA and the MFC dysplastic features.

Keywords

Myelodysplastic syndrome, cytogenetic aberrancies, flow cytometry, dysplasia assessment.