MDS is a heterogeneous clonal disorder associated with ineffective hematopoiesis, reduced blood cells, and hematopoietic cells' dysplasia. Generally, MDS is known as a preleukemic disorder and is considered an elderly disease. Indeed, the mean age of patients in our study was 66 years, with a range of 50–76 years, which is similar to MDS in the US population (67 years) (11), and close to Turkey (69 years) (12) and European countries such as Germany (70 years) (13) and Poland (14) (70 years). On the other hand, our results are significantly different from those of East Asian countries such as China (49 years) (15), India (42, 45, and 55 years) (16–18), and Japan (76 years) (19). Most of the patients were farmers or worked in petroleum jobs. It is worth noting that most of the farmers in the southwest regions of Iran, where our study was conducted, are exposed to pesticides. The association of pesticide exposure and MDS incidence was recently confirmed in a meta-analysis study (20). Moreover, many investigators reported that petroleum workers exposed to benzene had an important MDS risk factor (21, 22). The male to female ratio was 2.6:1, which was clearly higher than those reported from the US (1.9: 1) (11), Korea (1.7: 1) (23), China (1.3: 1) (15), and Pakistan (1.7: 1) (24). In Iranian culture, women do not work as much as men, especially the high-risk jobs, which might explain the higher male: female ratio in our study compared to other reports.
The mean hemoglobin level in our study on southwest Iranian patients was 9.9 g / dl, which is similar to that obtained in Turkey (9 g / dl) (12) and Greece (9.5 g / dl) (25). However, our hemoglobin data are higher than those obtained in Pakistan (7.7 g / dl), China (6.3 g / dl) (15), Singapore (7.7 g / dl) (26), and India (6.84 g / dl) (18). The difference may be due to the higher percentage of males in our study and the fact that Iran implements a national iron supplementation program. On the other hand, the mean platelet counts in our study was 103 × 103 / µl, which is similar to those obtained by Lau et al. in Singapore (101×103 / µl) (26). However, our data on platelets counts are higher than those obtained by Chen et al. in China (42×103 / µl) (15), Ehsan et al. in Pakistan (60 ×103 / µl), and Chaubey et al. in India (85 × 103 / µl)(18). Noteworthy that even higher platelet counts were reported in Turkey (163×103 µl) (12) and Greece (158 × 103 / µl) (25).
Although our study included patients from the 2014 to 2018 period, all patients were re-classified according to the 2016 revision of the World Health Organization classification of myeloid neoplasms and acute leukemia (6). Our data showed that the most common MDS subgroup was MDS-MLD (36.9%), followed by MDS-SLD (18.4%). These results are in line with those of Haase et al. in Germany (27) and Rashid et al. in Pakistan (28), who reported that MDS-MLD is the most common subtype (27.6% and 52.1%, respectively). Moreover, Pozdnyakova et al. in the USA (11) and Li et al. in China (29) reported that MDS-MLD was the most common subgroup (Respectively 32.2% and 44%) followed by MDS-EB-I. In contrast, Chauby et al. reported MDS-SLD as the most common type of MDS in India (18). The aforementioned differences might be due to the different ethnicity, population of the study, and/or sensitivity of the applied laboratory assay.
Cytogenetic abnormalities play a substantial role in the pathogenesis of MDS and are key factors in the diagnosis, classification, and prognostic scoring of the disease. However, the pathogenesis of MDS is still not well understood in Iran. The environmental, occupational, and genetic factors in Iran's southwest region are very different from western countries. This would affect the pathogenesis of MDS and may cause various chromosomal abnormalities, different frequencies, and patterns of MDS subtypes. Chromosomal abnormalities were observed in 42.7% of the patients, in accordance to other studies conducted in different parts of the world such as in Pakistan (42.3%) (28), the United States (44.5%) (11), Germany (49.8%) (27), Tunisia (51%) (30), and India (47.5%) (18). However, this was less than what was found in China (67.5%) (29). Among patients with abnormal karyotypes, 72.7% had a single abnormality, 20.5% had double abnormalities, while 6.8% had complex abnormalities (more than 3 abnormalities). The prognostic score of the studied patients was assessed according to R-IPSS. Accordingly, more than 91.3% of patients had very good, good, and intermediate prognosis. However, the poor prognosis was observed in only 9 cases, and very poor prognosis was observed in none of the patients.
In this study, the most common chromosomal abnormality was trisomy 8 (13.6% of all patients and 31.8% of patients with abnormal karyotype), followed by dell 17p (8.7% of all patients and 20.5% of patients with abnormal karyotype). Trisomy 8 was observed in 10 patients as a single chromosomal abnormality, in 2 patients with double chromosomal abnormalities, and in 2 patients with a complex karyotype. In accordance, Li et al. in China (29) and Rashid et al. in Pakistan (28) showed that the most common chromosomal abnormality was trisomy 8. In contrast, the most common chromosomal abnormality in Tunisia (30), Germany (27), Switzerland (31), Greece (25), and the United States (11) was − 5 / del (5q). Our results showed that chromosomal abnormalities in Iranian MDS patients often include changes in the copy number (except for 2 cases), including deletion of all or part of a chromosome (e.g., dell 17p or monosomy 7) or gain of a chromosome (e.g., trisomy 8), while balance abnormalities (such as translocations) have a very low incidence in patients. The changes in copy numbers result in a change in the dosage of genes, which can lead to the inactivation of tumor suppressor genes and the activation of oncogenes by various mechanisms such as haploinsufficiency and loss of heterozygosity, thus playing an essential role in the initiation and progression of the disease. For instance, it has been shown that the CUX1 gene, expressed on chromosome 7, acts as a tumor suppressor gene in myeloid precursors, decreases in MDS (and AML) with − 7 / del (7q), and is involved in the pathogenesis of the disease (32). It is worth noting that MDS cells with trisomy 8 (+ 8) express high levels of antiapoptotic proteins and have high resistance to apoptotic agents, such as gamma rays (33).
There has not been such a registry developed to capture the MDS epidemiology in Iran yet. So, we will be the pioneer to report the Clinico-Hematological and cytogenetic spectrum of adult myelodysplastic syndrome in addition to the plethora of scientific information that is already available in the western and eastern literature.