The specific distribution pattern of IKZF1 mutation in acute myeloid leukemia
JOURNAL OF HEMATOLOGY & ONCOLOGY
Authors: Zhang, Xiang; Zhang, Xuewu; Li, Xia; Lv, Yunfei; Zhu, Yanan; Wang, Jinghan; Jin, Jie; Yu, Wenjuan
Abstract
IKZF1 belongs to the IKAROS family of transcription factors, and its deletion/mutation frequently affects acute lymphoblastic leukemia. In acute myeloid leukemia, IKZF1 deletion has been demonstrated recurrent, but whether IKZF1 mutation also exists in AML remained largely unknown. Herein, we analyzed the IKZF1 mutation in AML. In our cohort, the frequency of IKZF1 mutation was 2.6% (5/193), and 5 frameshift/nonsense mutations as well as 2 missense mutations were identified in total. Molecularly, IKZF1 mutation was absent in fusion gene-positive AML, but it was demonstrated as the significant concomitant genetic alteration with SF3B1 or bi-alleleCEBPA mutation in AML. Clinically, two IKZF1, PTPN11 and SF3B1-mutated AML patients exhibited one aggressive clinical course and showed primary resistant to chemotherapy. Furthermore, we confirmed the recurrent IKZF1 mutation in AML with cBioPortal tool from OHSU, TCGA and TARGET studies. Interestingly, OHSU study also showed that SF3B1 mutation was the significant concomitant genetic alteration with IKZF1 mutation, indicating their strong synergy in leukemogenesis. In conclusion, IKZF1 mutation recurrently affected AML.
Clinicopathological and prognostic significance of SHP2 and Hook1 expression in patients with thyroid carcinoma
HUMAN PATHOLOGY
Authors: Cao, Jun; Huang, Yu-Qing; Jiao-Sun; Lan, Xia-Bin; Ge, Ming-Hua
Abstract
Some thyroid carcinomas (TCs) have an aggressive biological behavior and poor prognosis, and lacking of effective molecular markers is still the main obstacle for clinical stratified diagnosis and treatment of TC. The aim of the study was to discover the clinicopathological and prognostic implications of Src homology region 2-containing protein tyrosine phosphatase 2 (SHP2) and Hook microtubule tethering protein I (Hook1) expression in TC. The expression of SHP2 and Hook1 was detected by immunohistochemistry on tissue microarrays from 313 primary TCs who underwent surgery in January 2006 and January 2010 in Zhejiang Cancer Hospital. The chi(2) test, Kaplan-Meier method, and Cox proportional-hazards regression models were used to analyze the associations between their expressions and clinicopathological features and prognosis. The expression rates of SHP2 and Hook1 in TC were 57.5% (180/313) and 22.0% (69/313), respectively. SHP2 was positively correlated with Hook1 in TC. SHP2 expression differed significantly by age, histologic variants, maximal tumor diameter, intrathyroidal dissemination, metastases, and disease stage (P < .05). Moreover, patients with high SHP2 expression had reduced risk for death of disease compared with those with low SHP2 expression (hazard ratio, 0.267; 95% confidence interval, 0.105-0.684; P = .006) in univariate analysis, but that multivariate analysis failed to suggest that SHP2 was an independent prognostic factor. Hook1 expression differed significantly by histologic variants, maximal tumor diameter, and intrathyroidal dissemination (P < .05). However, there was no significant correlation between Hook1 expression and outcome in TC (P > .05). Our results suggested that SHP2 may be a favorable indicator of prognosis in TC. (C) 2018 Elsevier Inc. All rights reserved.