Deregulated expression in Ph+ human leukemias of AHI-1, a gene activated by insertional mutagenesis in mouse models of leukemia

Jiang, Xiaoyan; Zhao, Yun; Chan, Wing Yiu; Vercauteren, Suzanne; Pang, Emily; Kennedy, Sean; Nicolini, Frank; Eaves, Allen C.; Eaves, Connie J.

doi:10.1182/blood-2003-11-4026

Cited by 43 publications

(51 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Notably, higher levels of AHI-1 shorter isoforms were present in Hut78 cells, as reported previously. 5 These results provide evidence of splicing perturbations affecting AHI-1 expression at RNA and protein levels in primary leukemic Sezary cells.…”

Section: Deregulated Ahi-1 Expression Is Present In Leukemic Sezary Cmentioning

confidence: 55%

“…In addition, AHI-1 transcript levels are found to be significantly increased in a chronic myeloid leukemia (CML) cell line (K562) and in primary leukemic cells with Philadelphia chromosome-positive (Ph þ ), but not Ph À leukemias, especially in highly enriched leukemic stem cells from patients with CML. 5 These results suggest that downregulation of Ahi-1/AHI-1 expression is an important conserved step in primitive normal hematopoietic cell differentiation and that perturbations in AHI-1 expression may contribute to the development of specific types of human leukemia and lymphomas.…”

Section: Introductionmentioning

confidence: 90%

“…Specific primers to detect all AHI-1 isoforms and optimal conditions for the amplification of these gene products and for normalization of the C t values of the gene of interest to that of GAPDH were described previously. 5,28 Northern blot analysis…”

Section: Quantitative Real-time Rt-pcr Analyses (Q-rt-pcr)mentioning

confidence: 99%

“…To investigate directly whether deregulated expression of AHI-1 in human leukemic cells contributes to their transformed properties, knockdown of AHI-1 expression in Hut78 cells, a cell line that shows highly deregulated AHI-1 expression, 5 was performed using retroviral-mediated RNAi. 22,23 Hut78 cells are characterized by several interesting transforming phenotypes, including growth factor independence, autocrine production of IL-2, IL-4, TNFa and interferon-g (IFN-g), and induction of tumors in mice.…”

Section: Stable Suppression Of Ahi-1 Expression Decreases Autocrine Pmentioning

confidence: 99%

“…1 We have recently demonstrated that Ahi-1/AHI-1 expression is regulated at multiple stages of hematopoiesis in a manner that is highly conserved between mouse and humans. 5 Ahi-1/AHI-1 is expressed at its highest level in the most primitive hematopoietic cells and is then rapidly downregulated as the cells begin to differentiate. Interestingly, marked deregulation of AHI-1 expression is seen in a broad spectrum of human leukemic cell lines, particularly in the cutaneous T-cell lymphoma cell (CTCL) lines, Hut78, derived from the blood of a patient with Sezary syndrome (SS), and Hut102, derived from blood of a patient with mycosis fungoides (MF), where increases in AHI-1 transcripts of 40-fold are seen.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Evidence for an oncogenic role of AHI-1 in Sezary syndrome, a leukemic variant of human cutaneous T-cell lymphomas

et al. 2006

View full text Add to dashboard Cite

Section: Deregulated Ahi-1 Expression Is Present In Leukemic Sezary Cmentioning

confidence: 55%

Section: Introductionmentioning

confidence: 90%

Section: Quantitative Real-time Rt-pcr Analyses (Q-rt-pcr)mentioning

confidence: 99%

Section: Stable Suppression Of Ahi-1 Expression Decreases Autocrine Pmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Evidence for an oncogenic role of AHI-1 in Sezary syndrome, a leukemic variant of human cutaneous T-cell lymphomas

et al. 2006

View full text Add to dashboard Cite

Association of Single-Nucleotide Variants in the Human Leukocyte Antigen and Other Loci With Childhood Hodgkin Lymphoma

et al. 2022

View full text Add to dashboard Cite

IMPORTANCEStudies focusing on genetic susceptibility of childhood Hodgkin lymphoma (HL) are limited. OBJECTIVES To identify genetic variants associated with childhood-onset HL vs adult-onset HL. DESIGN, SETTING, AND PARTICIPANTS This genetic association study was performed with 3 cohorts: the St Jude Lifetime Cohort Study (SJLIFE), initiated in 2007 with ongoing follow-up, and the original and expansion cohorts of the Childhood Cancer Survivor Study (CCSS), initiated in the 1990s with ongoing follow-up. Results of these genome-wide association studies (GWASs) were combined via meta-analysis. Data were analyzed from June 2021 to June 2022. MAIN OUTCOMES AND MEASURES Childhood HL was the focused outcome. Single-nucleotide variant (SNV, formerly single-nucleotide polymorphism) array genotyping and imputation were conducted for the CCSS original cohort, and whole-genome sequencing was performed for the SJLIFE and CCSS expansion cohort.RESULTS A total of 1286 HL cases (mean diagnosis [SD] age, 14.6 [3.9] years), 6193 non-HL childhood cancer cases, and 369 noncancer controls, all of European ancestry, were included in the analysis. Using step-wise conditional logistic regression, the odds ratios (ORs) for each of the 3 independent SNVs identified in the human leukocyte antigen (HLA) locus were 1.80 (95% CI, 1.59-2.03;

show abstract

Genome‐Wide Association Meta‐Analysis Reveals Novel Juvenile Idiopathic Arthritis Susceptibility Loci

McIntosh

Marion

Sudman

et al. 2017

Arthritis & Rheumatology

View full text Add to dashboard Cite

Objective Juvenile idiopathic arthritis (JIA) is the most common childhood rheumatic disease and has a strong genomic component. To date, JIA genetic association studies have had limited sample sizes, used heterogeneous patient populations, or included only candidate regions. The aim of this study was to identify new associations between JIA patients with oligoarticular disease and those with IgM rheumatoid factor (RF)–negative polyarticular disease, which are clinically similar and the most prevalent JIA disease subtypes. Methods Three cohorts comprising 2,751 patients with oligoarticular or RF-negative polyarticular JIA were genotyped using the Affymetrix Genome-Wide SNP Array 6.0 or the Illumina HumanCoreExome-12+ Array. Overall, 15,886 local and out-of-study controls, typed on these platforms or the Illumina HumanOmni2.5, were used for association analyses. High-quality single-nucleotide polymorphisms (SNPs) were used for imputation to 1000 Genomes prior to SNP association analysis. Results Meta-analysis showed evidence of association (P < 1 × 10−6) at 9 regions: PRR9_LOR (P = 5.12 × 10−8), ILDR1_CD86 (P = 6.73 × 10−8), WDFY4 (P = 1.79 × 10−7), PTH1R (P = 1.87 × 10−7), RNF215 (P = 3.09 × 10−7), AHI1_LINC00271 (P = 3.48 × 10−7), JAK1 (P = 4.18 × 10−7), LINC00951 (P = 5.80 × 10−7), and HBP1 (P = 7.29 × 10−7). Of these, PRR9_LOR, ILDR1_CD86, RNF215, LINC00951, and HBP1 were shown, for the first time, to be autoimmune disease susceptibility loci. Furthermore, associated SNPs included cis expression quantitative trait loci for WDFY4, CCDC12, MTP18, SF3A1, AHI1, COG5, HBP1, and GPR22. Conclusion This study provides evidence of both unique JIA risk loci and risk loci overlapping between JIA and other autoimmune diseases. These newly associated SNPs are shown to influence gene expression, and their bounding regions tie into molecular pathways of immunologic relevance. Thus, they likely represent regions that contribute to the pathology of oligoarticular JIA and RF-negative polyarticular JIA.

show abstract

Deregulated expression in Ph+ human leukemias of AHI-1, a gene activated by insertional mutagenesis in mouse models of leukemia

Cited by 43 publications

References 37 publications

Evidence for an oncogenic role of AHI-1 in Sezary syndrome, a leukemic variant of human cutaneous T-cell lymphomas

Evidence for an oncogenic role of AHI-1 in Sezary syndrome, a leukemic variant of human cutaneous T-cell lymphomas

Association of Single-Nucleotide Variants in the Human Leukocyte Antigen and Other Loci With Childhood Hodgkin Lymphoma

Genome‐Wide Association Meta‐Analysis Reveals Novel Juvenile Idiopathic Arthritis Susceptibility Loci

Contact Info

Product

Resources

About