Distinct mutation profile and prognostic relevance in patients with hypoplastic myelodysplastic syndromes (h-MDS)

// Chi-Yuan Yao 1, * , Hsin-An Hou 1, * , Tzung-Yi Lin 1 , Chien-Chin Lin 1, 2 , Wen-Chien Chou 1, 2 , Mei-Hsuan Tseng 1 , Ying-Chieh Chiang 1 , Ming-Chih Liu 3 , Chia-Wen Liu 3 , Yuan-Yeh Kuo 4 , Shang-Ju Wu 1 , Xiu-Wen Liao 5 , Chien-Ting Lin 1, 5 , Bor-Shen Ko 1 , Chien-Yuan Chen 1 , Szu-Chun Hsu 2 , Chi-Cheng Li 5 , Shang-Yi Huang 1 , Ming Yao 1 , Jih-Luh Tang 1, 5 , Woei Tsay 1 , Chieh-Yu Liu 6 , Hwei-Fang Tien 1 1 Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan 2 Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan 3 Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan 4 Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan 5 Tai-Cheng Stem Cell Therapy Center, National Taiwan University, Taipei, Taiwan 6 Biostatistics Consulting Laboratory, Department of Nursing, National Taipei College of Nursing, Taipei, Taiwan * These authors have contributed equally to this work Correspondence to: Hwei-Fang Tien, email: hftien@ntu.edu.tw Keywords: myelodysplastic syndromes, bone marrow hypocellularity, revised international prognostic scoring system, gene mutation, prognosis Received: April 14, 2016 Accepted: July 10, 2016 Published: August 4, 2016 ABSTRACT Myelodysplastic syndromes (MDS) are a heterogeneous group of hematologic malignancies. Although most MDS patients have normal or increased BM cellularity (NH-MDS), some have hypocellular BM (h-MDS). The reports concerning the differences in genetic alterations between h-MDS and NH-MDS patients are limited. In this study, 369 MDS patients diagnosed according to the WHO 2008 criteria were recruited. h-MDS patients had lower PB white blood cell and blast counts, and lower BM blast percentages, than those with NH-MDS. h-MDS was closely associated with lower-risk MDS, defined by the International Prognostic Scoring System (IPSS) and revised IPSS (IPSS-R). IPSS-R could properly predict the prognosis in h-MDS ( P <0.001) as in NH-MDS patients. The h-MDS patients had lower incidences of RUNX1, ASXL1, DNMT3A, EZH2 and TP53 mutations than NH-MDS patients. The cumulated incidence of acute leukemic transformation at 5 years was 19.3% for h-MDS and 40.4% for NH-MDS patients ( P= 0.001). Further, the patients with h-MDS had longer overall survival (OS) than those with NH-MDS ( P= 0.001), and BM hypocellularity remains an independent favorable prognostic factor for OS irrespective of age, IPSS-R, and gene mutations. Our findings provide evidence that h-MDS indeed represent a distinct clinico-biological subgroup of MDS and can predict better leukemia-free survival and OS.