Genetic analysis of Ikaros target genes and tumor suppressor function in BCR-ABL1+ pre–B ALL

Schjerven, Hilde; Ayongaba, Etapong F.; Aghajanirefah, Ali; McLaughlin, Jami; Cheng, Donghui; Geng, Huimin; Boyd, Joseph R.; Eggesbø, Linn M; Lindeman, Ida; Heath, Jessica L.; Park, Eugene; Witte, Owen N.; Smale, Stephen T.; Frietze, Seth; Müschen, Markus

doi:10.1084/jem.20160049

Cited by 42 publications

(62 citation statements)

References 86 publications

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“…There is emerging evidence that targeting IKAROS family proteins is feasible, mainly through post-translation modification, and is effective in therapeutic applications [102]. IKAROS has shown tumor suppressor activity in the lymphoid lineage in mouse models [103,105]. The mechanisms by which IKAROS functions as tumor suppressor in pre-B ALL remain poorly understood [105].…”

Section: Ikaros Protein and Ikzh1 Genementioning

confidence: 99%

“…IKAROS has shown tumor suppressor activity in the lymphoid lineage in mouse models [103,105]. The mechanisms by which IKAROS functions as tumor suppressor in pre-B ALL remain poorly understood [105]. Also, the mechanism by which deletion of IKZF1 gene influences the pathogenesis of pre-B ALL is still unclear [106].…”

Section: Ikaros Protein and Ikzh1 Genementioning

confidence: 99%

“…Also, the mechanism by which deletion of IKZF1 gene influences the pathogenesis of pre-B ALL is still unclear [106]. Inactivation of the tumor suppressor gene IKZF1 encoding the transcriptional regulator IKAROS is the hallmark of BCR-ABL1 positive pre-B ALL [105]. Genetic depletion of different IKAROS targets including CTNND1 and the early hematopoietic cell surface marker CD34 has resulted in reduced leukemic growth [105].…”

Section: Ikaros Protein and Ikzh1 Genementioning

confidence: 99%

“…Inactivation of the tumor suppressor gene IKZF1 encoding the transcriptional regulator IKAROS is the hallmark of BCR-ABL1 positive pre-B ALL [105]. Genetic depletion of different IKAROS targets including CTNND1 and the early hematopoietic cell surface marker CD34 has resulted in reduced leukemic growth [105]. Elevated CTNND1 expression contributes to maintenance of murine B-ALL cells with compromised IKAROS function [105].…”

Section: Ikaros Protein and Ikzh1 Genementioning

confidence: 99%

“…Genetic depletion of different IKAROS targets including CTNND1 and the early hematopoietic cell surface marker CD34 has resulted in reduced leukemic growth [105]. Elevated CTNND1 expression contributes to maintenance of murine B-ALL cells with compromised IKAROS function [105].…”

Section: Ikaros Protein and Ikzh1 Genementioning

confidence: 99%

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Cytogenetics, Molecular Genetics and Epigenetics and Their Impact on The Management of Acute Lymphoblastic Leukemia

Wk¹,

Dridi²,

Ka³

2017

J Mol Genet Med

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The recent improvements in the outcomes of patients with acute lymphoblastic leukemia reflect the progress in the field of diagnostics and the achievements in therapeutic interventions. In particular, the availability of more advanced technology in the cytogenetic and molecular laboratories has resulted in the stratification of patients into specific risk groups and thus several novel agents as well as targeted therapies have been introduced. Additionally, precision medicine will be applicable in the near future and thus the recent developments will facilitate the provision of safer modalities of therapy that may ultimately yield not only higher responses but also improved survival rates.This review represents a recent update on the role of various cytogenetic assays and molecular techniques in patients with acute lymphoblastic leukemia. It is composed of a number of sections including: history of cytogenetics, disease etiology and pathophysiology, utilization of various cytogenetic assays diagnostically, disease-specific cytogenetic and molecular abnormalities, common disease genetic subtypes, prognosis and risk stratification, refractory and relapsed disease, novel therapies, precision medicine and drug repurposing.

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Section: Ikaros Protein and Ikzh1 Genementioning

confidence: 99%

Section: Ikaros Protein and Ikzh1 Genementioning

confidence: 99%

Section: Ikaros Protein and Ikzh1 Genementioning

confidence: 99%

Section: Ikaros Protein and Ikzh1 Genementioning

confidence: 99%

Section: Ikaros Protein and Ikzh1 Genementioning

confidence: 99%

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Cytogenetics, Molecular Genetics and Epigenetics and Their Impact on The Management of Acute Lymphoblastic Leukemia

Wk¹,

Dridi²,

Ka³

2017

J Mol Genet Med

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High CD34 surface expression in BCP‐ALL predicts poor induction therapy response and is associated with altered expression of genes related to cell migration and adhesion

et al. 2022

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Puppet masters of B‐cell progenitor acute lymphoblastic leukemia: The preB cell receptor and the interleukin 7 receptor α

Gupta

Lohoff

2023

Eur J Immunol

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B‐cell progenitor acute lymphoblastic leukemia (BCP‐ALL) is enriched for a preB cell phenotype, hinting at a specific vulnerability of this cell stage. Two signaling pathways via the preB cell receptor (preBCR) and the interleukin 7 receptor α (IL‐7Rα) chain govern the balance between differentiation and proliferation at this stage and both receptor pathways are routinely altered in human BCP‐ALL. Here, we review the immunobiology of both the preBCR as well as the IL‐7Rα and analyze the human BCP‐ALL spectrum in the light of these signaling complexes. Finally, we present a terminology for preBCR signaling modules that distinguishes a pro‐proliferative “phase‐I” module from a pro‐differentiative “phase‐II” module. This terminology might serve as a framework to better address shared oncogenic mechanics of preB cell stage BCP‐ALL.

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Genetic analysis of Ikaros target genes and tumor suppressor function in BCR-ABL1+ pre–B ALL

Cited by 42 publications

References 86 publications

Cytogenetics, Molecular Genetics and Epigenetics and Their Impact on The Management of Acute Lymphoblastic Leukemia

Cytogenetics, Molecular Genetics and Epigenetics and Their Impact on The Management of Acute Lymphoblastic Leukemia

High CD34 surface expression in BCP‐ALL predicts poor induction therapy response and is associated with altered expression of genes related to cell migration and adhesion

Puppet masters of B‐cell progenitor acute lymphoblastic leukemia: The preB cell receptor and the interleukin 7 receptor α

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