Asian Population Is More Prone to Develop High-Risk Myelodysplastic Syndrome, Concordantly with Their Propensity to Exhibit High-Risk Cytogenetic Aberrations

Abstract

This study explores the hypothesis that genetic differences related to an ethnic factor may underlie differences in phenotypic expression of myelodysplastic syndrome (MDS). First, to identify clear ethnic differences, we systematically compared the epidemiology, and the clinical, biological and genetic characteristics of MDS between Asian and Western countries over the last 20 years. Asian MDS cases show a 2- to 4-fold lower incidence and a 10-year younger age of onset compared to the Western cases. A higher proportion of Western MDS patients fall into the very low- and low-risk categories while the intermediate, high and very high-risk groups are more represented in Asian MDS patients according to the Revised International Prognostic Scoring System. Next, we investigated whether differences in prognostic risk scores could find their origin in differential cytogenetic profiles. We found that 5q deletion (del(5q)) aberrations and mutations in TET2, SF3B1, SRSF2 and IDH1/2 are more frequently reported in Western MDS patients while trisomy 8, del(20q), U2AF1 and ETV6 mutations are more frequent in Asian MDS patients. Treatment approaches differ between Western and Asian countries owing to the above discrepancies, but the overall survival rate within each prognostic group is similar for Western and Asian MDS patients. Altogether, our study highlights greater risk MDS in Asians supported by their cytogenetic profile.

Should We Look beyond Revised International Prognostic Scoring System: A Retrospective Observational Study of Progression of Myelodysplastic Syndrome to Acute Leukemia

“…Maximum number of cases belonged to MDS-EB category accounting to 48 cases (76.1%) and 37 cases (68.5%) belonged to high or very high risk group which is supported by an Asian study which discusses the regional differences in CG. 24 Cytogenetic information plays crucial role along with degree of dysplasia and blast percentage in risk stratification of de novo MDS by using IPSS-R scoring system and is able to predict the risk of progression to AL ( Table 3 ). From a total of 15 cases which progressed to AL, 13 cases belonged to high and very high risk groups, but interestingly 10 cases (66.67%) belonged to good cytogenetic group and consisted of normal karyotyping (eight cases) and del 5q (two cases) and these findings were supported by the Indian study as well.…”

TP53 in Myelodysplastic Syndromes

“…MDS occurs mainly in the elderly. At diagnosis, the median age is ~76 years old in Europe and almost 10 years younger in Asian MDS patients [ 12 ]. About 44% of healthy individuals at 50 years of age may have at least one hematopoietic stem/progenitor cell (HSPC) that carries a randomly generated functional TP53 mutation.…”

“…However, as for all classification systems, variables outside the current parameters prompt further refinements in prognostic scoring systems, in which gene variants have been identified in recent studies, contributing to the clinical heterogeneity of the disease course and influencing the prognosis of patients [ 10 , 11 ]. Notably, TP53 mutations, with an overall incidence of about 10% in de novo MDS and 40% in therapy-related MDS (t-MDS patients) [ 12 , 13 ], is independently associated with resistance to conventional therapies, rapid transformation to AML, and a poor outcome [ 14 ]. Of note, in MDS cases with five or more karyotype abnormalities, the absence of TP53 mutations is associated with a much better survival compared to those with TP53 mutations [ 15 ].…”

Is race important in genomic classification of hematological neoplasms?

“…[4][5][6] For example, it is well known that there are racial differences in cytogenetic and mutational topographies of persons with MDS. [7][8][9][10][11] It is generally believed that del (5q) and mutations in SF3B1, TET2 and SRSF2 are more common in…”

“…These frequencies are like prior reports in Asians. 9,11 These distributions are displayed in Figure S2. Compared with the EuroMDS cohort, fewer of our subjects were classified as groups 1 (4% vs.17%; p < 0.001) and 6 (6% vs. 18%; p < 0.001; Table 1) in which the most common genetic abnormalities were SF3B1 mutation and/or del(5q).…”