First Cytogenetic Profile of Omani Patients with de novo Myelodysplastic Syndromes Comparison with data from Asia , Africa , Europe and North and South America *

Clonal cytogenetic abnormalities have been reported among 30–80% of patients with myelodysplastic syndromes (MDS); however, 20–70% of patients with MDS show a normal karyotype that may nevertheless harbour a cryptic genetic alteration. Earlier reports have suggested that the distribution of specific chromosomal aberrations varies among Western and Asian countries, with geographical and ethnic differences in the frequency of specific chromosomal aberrations. This article compared the cytogenetic data of 36 adult Omani patients with MDS to previously reported data from other populations. Differences were noted between the percentages of clonal aberrations and the median age of Omani subjects at presentation in comparison to individuals of different ethnicities and from various geographical locations. To the best of the authors’ knowledge, this is the first report to describe the cytogenetic data of patients with MDS from Oman.

M yelodysplastic syndromes (mds) are a group of clonal haematopoietic stem cell diseases characterised by cytopaenia, dysplasia in one or more of the major myeloid cell lines, ineffective haematopoiesis and an increased risk of developing acute myeloid leukaemia (AML). 1 Cytogenetic and molecular abnormalities are key elements in the diagnosis of MDS.Clonal chromosomal abnormalities in MDS have been observed in 30-80% of patients, depending on the subtype and whether it is de novo or mutageninduced. 2,3][9] Over time, MDS has been increasingly recognised as a cause of bone marrow failure; however, the precise incidence of de novo MDS is unknown. 10Jacobs et al. have suggested that the distribution of specific chromosomal aberrations in MDS varies between Western and Asian countries. 11Another report also indicated geographical and ethnic differences in the frequency of specific chromosomal aberrations. 12he incidence of chromosomal abnormalities in Indian population has been reported to vary from 37.5-88%. 13In addition, the frequency of chromosomal abnormalities varies between 37-50% in China, Thailand, Hong Kong and Japan. 13,14Complex aberrations have been more frequently observed in Indian patients as compared to those from other Asian countries. 13s such, ethnic and/or geographical differences could be heterogeneous and contribute to clinical, cytogenetic or molecular events leading to MDS.6][17][18][19][20][21][22] To the best of the authors' knowledge, this is the first report detailing the cytogenetic profile of Omani patients with MDS.In order to analyse ethno-geographical differences in the pathogenesis of MDS, the current article aimed to compare the cytogenetic findings of Omani patients with de novo MDS with available data from Europe, North and South America, Africa and other Asian countries.

Methods
Data were collected from all patients with MDS presenting between 2006-2013 to the Department of Haematology at the Sultan Qaboos University Hospital (SQUH), a tertiary care centre in Muscat, Oman.A diagnosis of MDS was made as per the criteria of the World Health Organization (WHO). 23atients who did not fulfill the WHO criteria were excluded.All eligible subjects subsequently had their peripheral blood count recorded.In addition, bone marrow samples were obtained prior to the initiation of any therapy.
Cytogenetic analysis of the bone marrow samples was performed using GTG banding, with karyotypes reported according to the International System for Human Cytogenomic Nomenclature. 24At least 20 metaphases were karyotyped and analysed from 24-and 48-hour bone marrow cultures.Clonal    1].The median follow-up period was 28 months (range: 3-70 months).Table 2 shows the distribution of MDS subtypes according to age and gender.
Overall, 26 patients (72.2%) had normal karyotypes which indicated a good prognosis according to the Revised International Prognostic Scoring System (IPSS-R) [Table 3]. 25 One patient had a normal variant and another had a non-clonal abnormality.Eight patients had abnormal karyotypes (22.2%), of which two patients had clones which had trisomy 8 and one patient each had trisomy 21, a del(5)(q15q31) abnormality, a del(11)(q23) abnormality, an i(17)(q10) abnormality, a del(18)(p11) abnormality and an absent Y chromosome [Table 4].Six of these eight patients also showed normal clones along with abnormal clones.

Comparison of Omani Data with Other Populations
]26,28,31 The median age of the patients in Tunisia was 60 years old. 22Brazilian patients had the youngest median age (29 years old). 27mong Omani patients, the male-to-female ratio was 1:1, which was in accordance with a sample from Thailand and close to ratios reported from Brazil (1.2:1) and Germany (1.3:1); 3,26,27 however, this finding was contrary to many other Asian countries and certain European, North American and African countries in which males outnumbered females. 7,11,13,15,22,28,30,31urther research is needed to determine a possible cause for this gender difference between populations.
The majority of Omani patients showed normal karyotypes (62.2%) and were believed to have a good prognosis according to IPSS-R classifications. 25nly published data on the frequency of abnormal karyotypes from Japan (23.9%) and China (37.1%) were close to the data from Oman. 16,28Chromosomal abnormalities such as i(17q), trisomy 21 and the absence of the Y chromosome were seen in one each of the Omani patients (2.8% each).Studies from Germany, Japan and Argentina also reported patients with loss of the Y chromosome (7.0%,1.1% and 2.7%, respectively); 3,15,29 however, this abnormality was not observed among patients from Thailand, Switzerland or Brazil. 7,26,27Similarly, trisomy 21 was not observed

Table 1 :
Characteristics of Omani patients with myelodysplastic syndromes presenting to the Sultan Qaboos University Hospital, Muscat, Oman (N = 36) First Cytogenetic Profile of Omani Patients with de novo Myelodysplastic Syndromes Comparison with data from Asia, Africa, Europe and North and South America e288 | SQU Medical Journal, August 2017, Volume 17, Issue 3 abnormalities were defined as two or more cells with the same whole chromosome gain/chromosome rearrangement or three or more cells with the same chromosome loss.A complex karyotype was defined as three or more cytogenetic abnormalities.

Table 2 :
Age/gender distribution across subtypes of Omani patients with myelodysplastic syndromes presenting to the Sultan Qaboos University Hospital, Muscat, Oman (N = 36)

Table 3 :
Cytogenetic prognosis of Omani patients with myelodysplastic syndromes presenting to the Sultan Qaboos University Hospital, Muscat, Oman (N = 36)

Table 4 :
23normal karyotypes among Omani patients with myelodysplastic syndromes presenting to the Sultan Qaboos University Hospital, Muscat, Oman (N = 36) Defined as per the criteria of the World Health Organization.23FirstCytogeneticProfile of Omani Patients with de novo Myelodysplastic SyndromesComparison with data from Asia, Africa, Europe and North and South America *e290 | SQU Medical Journal, August 2017, Volume 17, Issue 3