Expression of dominant-negative Ikaros isoforms and associated genetic alterations in Chinese adult patients with leukemia.
Dominant-negative (DN) Ikaros isoforms, having important roles in pathogenesis of leukemia, are mainly studied in pediatric patients, but little is known about Chinese adult patients. We examined 339 Chinese adult patients with leukemia and demonstrated the different findings between our results and those in several previous studies showing that DN isoforms overexpressed in Philadelphia chromosome positive acute lymphoblastic leukemia (Ph(+)ALL) and lymphoid/mixed blast crisis of chronic myelogenous leukemia. We confirmed that deletion of IKZF1 gene exons 4-7 is responsible for the generation of Ikaros 6 (Ik6). Moreover, we observed that expression of DN isoforms was dynamically consistent with BCR-ABL1 transcript levels, associated with higher incidence of relapse within 3 months or poor response to induction chemotherapy in Ph(+)ALL, correlated with high white blood cell, blast cells, CD34 positive cells, and delayed achieving complete hematological remission in ALL patients. In conclusion, this study provides a rationale for the integration of aberrant Ikaros isoforms, notably Ik6 and Ik10, in the evaluation of adult ALL, particularly in Ph(+)ALL patients.
Department of Hematology, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, 300 Guangzhou Road, Nanjing, 210029, China.
Ping
P
Liu
Zhongkun
Z
Lin
Sixuan
S
Qian
Chun
C
Qiao
Hairong
H
Qiu
Yujie
Y
Wu
Jianyong
J
Li
Zheng
Z
Ge
D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D045744:Cell Line, Tumor; D002648:Child; D015331:Cohort Studies; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D005799:Genes, Dominant / Q000235:genetics; D056726:Genetic Association Studies; D018922:HL-60 Cells; D006801:Humans; D051740:Ikaros Transcription Factor / Q000235:genetics*; D019169:Jurkat Cells; D020014:K562 Cells; D007938:Leukemia / Q000208:ethnology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010677:Philadelphia Chromosome; D020033:Protein Isoforms / Q000235:genetics; D020298:U937 Cells; D055815:Young Adult
C497239:IKZF1 protein, human; D020033:Protein Isoforms; D051740:Ikaros Transcription Factor