Distinct clinical and biological characteristics of acute myeloid leukemia with higher expression of long noncoding RNA KIAA0125
Journal
Annals of hematology
Journal Volume
100
Journal Issue
2
Pages
487 - 498
Date Issued
2021-02
Author(s)
Wang, Yu-Hung
Lee, Sze-Hwei
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.
Subjects
Acute myeloid leukemia; Chemoresistance; KIAA0125; Leukemic stem cell signatures; Long non-coding RNA
SDGs
Other Subjects
ABC transporter; cytarabine; idarubicin; long untranslated RNA; transcription factor RUNX1; long untranslated RNA; RNA; acute myeloid leukemia; adolescent; adult; aged; aging; Article; bioinformatics; bone marrow cell; cancer chemotherapy; cancer prognosis; cohort analysis; controlled study; disease free survival; drug megadose; drug resistance; female; gene expression; gene mutation; genetic association; hematopoietic stem cell; human; human cell; karyotype; KIAA0125 gene; leukemia remission; leukocyte count; major clinical study; male; overall survival; pathogenesis; priority journal; risk factor; RUNX1 gene; tumor suppressor gene; acute myeloid leukemia; biosynthesis; clinical trial; gene expression regulation; metabolism; middle aged; mortality; survival rate; very elderly; Adolescent; Adult; Aged; Aged, 80 and over; Disease-Free Survival; Female; Gene Expression Regulation, Leukemic; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; RNA, Long Noncoding; RNA, Neoplasm; Survival Rate
Publisher
SPRINGER
Type
journal article