Distinct clinical and biological characteristics of acute myeloid leukemia with higher expression of long noncoding RNA
- PDF / 1,715,140 Bytes
- 12 Pages / 595.276 x 790.866 pts Page_size
- 73 Downloads / 209 Views
ORIGINAL ARTICLE
Distinct clinical and biological characteristics of acute myeloid leukemia with higher expression of long noncoding RNA KIAA0125 Yu-Hung Wang 1,2 & Chien-Chin Lin 1,2,3 & Chia-Lang Hsu 4 & Sheng-Yu Hung 5 & Chi-Yuan Yao 3,5 & Sze-Hwei Lee 1,6 & Cheng-Hong Tsai 2 & Hsin-An Hou 2 & Wen-Chien Chou 2,3 & Hwei-Fang Tien 2 Received: 9 September 2020 / Accepted: 18 November 2020 # The Author(s) 2020
Abstract Expression of long non-coding RNA KIAA0125 has been incorporated in various gene expression signatures for prognostic prediction in acute myeloid leukemia (AML) patients, yet its functions and clinical significance remain unclear. This study aimed to investigate the clinical and biological characteristics of AML bearing different levels of KIAA0125. We profiled KIAA0125 expression levels in bone marrow cells from 347 de novo AML patients and found higher KIAA0125 expression was closely associated with RUNX1 mutation, but inversely correlated with t(8;21) and t(15;17) karyotypes. Among the 227 patients who received standard chemotherapy, those with higher KIAA0125 expression had a lower complete remission rate, shorter overall survival (OS) and disease-free survival (DFS) than those with lower expression. The prognostic significance was validated in both TCGA and GSE12417 cohorts. Subgroup analyses showed that higher KIAA0125 expression also predicted shorter DFS and OS in patients with normal karyotype or non-M3 AML. In multivariable analysis, higher KIAA0125 expression remained an adverse risk factor independent of age, WBC counts, karyotypes, and mutation patterns. Bioinformatics analyses revealed that higher KIAA0125 expression was associated with hematopoietic and leukemic stem cell signatures and ATP-binding cassette transporters, two predisposing factors for chemoresistance. Keywords Long non-coding RNA . KIAA0125 . Acute myeloid leukemia . Chemoresistance . Leukemic stem cell signatures
Introduction Yu-Hung Wang and Chien-Chin Lin contributed equally to this work. * Wen-Chien Chou [email protected] * Hwei-Fang Tien [email protected] 1
Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
2
Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, No. 7, Chung-Shan S. Rd, Taipei City 10002, Taiwan
3
Department of Laboratory Medicine, National Taiwan University Hospital, No. 7, Chung-Shan S. Rd, Taipei City 10002, Taiwan
4
Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
5
Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan
6
Tai-Cheng Stem Cell Therapy Center, National Taiwan University, Taipei, Taiwan
Long non-coding RNAs (lncRNAs) are non-protein coding RNAs that are longer than 200 nucleotides. Comparing to other classes of ncRNAs, lncRNAs exhibit a wide range of structures and functions [1]. Recently, lncRNAs have emerged as important regulators for gene expression via remodeling nuclear
Data Loading...
