title: Targeting of heme oxygenase-1 attenuates the negative impact of Ikaros isoform 6 in adult BCR-ABL1-positive B-ALL.
abstract: The correlation between Heme oxygenase-1 (HO-1) and dominant-negative Ikaros isoform 6 (IK6) is unclear. Firstly, we detected that IK6 existed in 20 of 42 (47.6%) adult BCR-ABL1-positive B-lineage acute lymphoblastic leukemia (BCR-ABL1-positive B-ALL) by using reverse transcribed polymerase chain reaction (PCR) and nucleotide sequencing. IK6-positive patients had an unfavorable outcome compared with IK6-negative ones. Further study showed that the level of HO-1 expression was higher in IK6-positive patients' samples than that in IK6-negative ones. And there was a strong correlation between the expression of IK6 and HO-1. The growth of primary CD34+ leukemic cells derived from our IK6-positive patients' pool was prohibited by silencing HO-1, further promoting their apoptosis. Furthermore, primary CD34+ leukemic cells derived from IK6-positive patients shown poor responses to imatinib in comparison with wild-type (IK1) patients, suggesting that the expression of IK6 resisted to imatinib in adult BCR-ABL1-positive B-ALL. Importantly, inhibition of HO-1 also increased their sensitivity to tyrosine kinase inhibitors (TKIs). Finally, we found that IK6 activated downstream STAT5, and HO-1 was one of the downstream target genes of STAT5. In conclusion, HO-1 is an essential survival factor in BCR-ABL1-positive B-ALL with IK6, and targeting HO-1 can attenuate the negative impact of IK6.
authors.affiliation: Clinical Medicine, Guizhou Medical University, Guiyang 550004, China.|Department of Hematology, The Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Hematology, The Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China.
authors.forename: Xingli
authors.initials: X
authors.lastname: Zou
authors.affiliation: Department of Hematology, The Affiliated Hospital of Guizhou Medical University, Guiyang 550004, China.|Department of Hematology, Guizhou Provincial Laboratory of Hematopoietic Stem Cell Transplantation Center, Guiyang 550004, China.
authors.forename: Ziming
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, The Affiliated Baiyun Hospital of Guizhou Medical University, Guiyang 550004, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Fang
authors.affiliation: Clinical Medicine, Guizhou Medical University, Guiyang 550004, China.|Department of Hematology, The Affiliated Hospital of Guizhou Medical University, Guiyang 550004, China.|Department of Hematology, Guizhou Provincial Laboratory of Hematopoietic Stem Cell Transplantation Center, Guiyang 550004, China.
authors.forename: Shuya
authors.initials: S
authors.lastname: Chen
authors.affiliation: Clinical Medicine, Guizhou Medical University, Guiyang 550004, China.|Department of Hematology, The Affiliated Hospital of Guizhou Medical University, Guiyang 550004, China.|Department of Hematology, Guizhou Provincial Laboratory of Hematopoietic Stem Cell Transplantation Center, Guiyang 550004, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Huang
authors.affiliation: Clinical Medicine, Guizhou Medical University, Guiyang 550004, China.|Department of Hematology, The Affiliated Hospital of Guizhou Medical University, Guiyang 550004, China.|Department of Hematology, Guizhou Provincial Laboratory of Hematopoietic Stem Cell Transplantation Center, Guiyang 550004, China.
authors.forename: Nana
authors.initials: N
authors.lastname: Zhe
authors.affiliation: Clinical Medicine, Guizhou Medical University, Guiyang 550004, China.|Department of Hematology, The Affiliated Hospital of Guizhou Medical University, Guiyang 550004, China.|Department of Hematology, Guizhou Provincial Laboratory of Hematopoietic Stem Cell Transplantation Center, Guiyang 550004, China.
authors.forename: Meisheng
authors.initials: M
authors.lastname: Yu
authors.affiliation: Department of Hematology, The Affiliated Hospital of Guizhou Medical University, Guiyang 550004, China.|Department of Hematology, Guizhou Provincial Laboratory of Hematopoietic Stem Cell Transplantation Center, Guiyang 550004, China.
authors.forename: Yaming
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Clinical Medicine, Guizhou Medical University, Guiyang 550004, China.|Department of Hematology, The Affiliated Hospital of Guizhou Medical University, Guiyang 550004, China.|Department of Hematology, Guizhou Provincial Laboratory of Hematopoietic Stem Cell Transplantation Center, Guiyang 550004, China.
authors.forename: Jishi
authors.initials: J
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018572:Disease-Free Survival; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006801:Humans; D051740:Ikaros Transcription Factor / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000378:metabolism* / Q000401:mortality; D055815:Young Adult
chemical_list: C586512:Ikaros 6 protein, human; D051740:Ikaros Transcription Factor; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D016044:Fusion Proteins, bcr-abl
keywords: BCR-ABL1-positive; IKZF1; STAT5; acute lymphoblastic leukemia; heme oxygenase-1