Gain of 1q as a Potential Adverse Prognostic Marker in Myelodysplastic Syndrome: Comparison with International Prognostic Scoring System Variables
Authors: Park Hyun-Kyung , Lee Dong Soon , Lee Hye Ryun , Cho Han Ik , Kim Hyun Kyung , Yoon Sung-Soo , Kim Byoung Kook 
Published: October 2019

Abstract
The gain of the 1q region, which is a recurrent chromosomal aberration in B lymphoproliferative disorder, has been reported one of the most common anomalies in Korean myelodysplastic patients. Recently, risk based application of hypomethylating agents or tailored therapy in MDS rely on the prognostic variables of International Prognostic Scoring System (IPSS). To investigate the possibility of 1q gain as a new prognostic marker, we evaluated the prognostic impact of 1q gain, along with comparison with IPSS variables. A total of 117 patients with newly diagnosed MDS between 1997 and 2007 at the Seoul National University Hospital were investigated. Fluorescence in situ hybridization (FISH) studies with 5 specific probe(EGR1 for 5q31 deletion, D7S522 for 7q31 deletion, CEP8, D20S108 for 20q12 deletion, LSI 1p36/1q25 for 1q gain) and conventional G-banding karyotyping were performed on bone marrow aspirates. Other laboratory findings, such as hemoglobin(Hb), absolute neutrophil count(ANC), platelet count, bone marrow blast percent and IPSS score, and clinical data were collected through the individual medical records. The median age was 54 years and the male-to-female ratio was 1.4. Using WHO classification, refractory anemia(RA) was 27.4% and the other subgroups as follows: RA with ringed sideroblast(RARS), 3.4%; refractory cytopenia with multilineage dysplasia(RCMD), 8.5%; RCMD with ringed sideroblasts(RCMD-RS), 0.9%; RA with excess blasts-1(RAEB-1), 26.5%; RAEB-2, 31.6%; and 5q- syndrome, 1.7%. Cytogenetic abnormalities by FISH and G-banding were detected in 58 patients (49.6%). Most frequent anomaly was trisomy 8 occuring in 28 patients(23.9% of the 117 patients, 48.3% of the 58 patients with clonal cytogenetic abnormalities). Gain of 1q was the second common anomalies seen in 18 patients (15.4%) and other anomalies were −7/del7q (13.7%), −5/del5q (13.7%), and del20q (2.6%). G-banding showed gain of 1q in 7 cases, additional 11 patients with gain of 1q were revealed by FISH only. Patients with 1q gain showed a poor survival (median survival 23 months; n=18) compared to patients without 1q gain (median survival 60 months; p=0.02). EGR1 and D7S522 deletion by FISH also had a shorter median survival (8 months vs. 60 months p=0.0001, 16 months vs. 60 months p=0.005). The initial platelet count and blast count were found to affect overall survival, whereas CEP8 FISH, D20S108 FISH, Hb and ANC did not. Our results show that gain of 1q is associated with an adverse clinical outcome and can be considered as a poor cytogenetic risk factor of IPSS. In the Western study, the prevalence of 1q gain was low because most studies report G-banding result only. But it may be increased up to 2.5 fold higher by using FISH analysis in combination with G-banding. A gain of 1q could be a candidate as an adverse prognostic marker in clinical practice, which could help for risk-adapted therapies.
Figure 1. Kaplan-Meier survival curve for chromosomal anomalies and IPSS. (A) gain of 1q. (B) −1/del(7q). (C) del(20q). Figure 1. Kaplan-Meier survival curve for chromosomal anomalies and IPSS. (A) gain of 1q. (B) −1/del(7q). (C) del(20q).