Differential role of Id1 in MLL-AF9–driven leukemia based on cell of origin

Man, Na; Sun, Xiao Jian; Tan, Yurong; Garcı́a-Cao, Marta; Liu, Fan; Cheng, Guangcun; Hatlen, Megan A.; Xu, Huiling; Shah, Ronit; Chastain, Nolan; Liu, Na; Huang, Gang; Zhou, Yuan; Sheng, Mengyao; Song, Junhong; Yang, Feng Chun; Benezra, Robert; Nimer, Stephen D.; Wang, Lan

doi:10.1182/blood-2015-11-677708

Cited by 14 publications

(13 citation statements)

References 24 publications

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“…Thus, to establish the authentic first-hit impact of the cALL oncogene ETV6-RUNX1 necessitates its expression in the transcriptional context of the appropriate developmental stage. Studies of both mouse and human embryonic hematopoiesis have demonstrated unique progenitor states during development ( Boiers et al., 2013 , Notta et al., 2015 ), and it is increasingly understood that oncogenic mutations can have distinct effects on cell fate in different developmental contexts ( Horton et al., 2013 , Man et al., 2016 , Porter et al., 2016 ). Understanding the interaction of leukemia-initiating mutations with developmentally restricted cell states requires a model of the relevant stages of human fetal B lymphopoiesis.…”

Section: Introductionmentioning

confidence: 99%

A Human IPS Model Implicates Embryonic B-Myeloid Fate Restriction as Developmental Susceptibility to B Acute Lymphoblastic Leukemia-Associated ETV6-RUNX1

et al. 2018

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SummaryETV6-RUNX1 is associated with childhood acute B-lymphoblastic leukemia (cALL) functioning as a first-hit mutation that initiates a clinically silent pre-leukemia in utero. Because lineage commitment hierarchies differ between embryo and adult, and the impact of oncogenes is cell-context dependent, we hypothesized that the childhood affiliation of ETV6-RUNX1 cALL reflects its origins in a progenitor unique to embryonic life. We characterize the first emerging B cells in first-trimester human embryos, identifying a developmentally restricted CD19−IL-7R+ progenitor compartment, which transitions from a myeloid to lymphoid program during ontogeny. This developmental series is recapitulated in differentiating human pluripotent stem cells (hPSCs), thereby providing a model for the initiation of cALL. Genome-engineered hPSCs expressing ETV6-RUNX1 from the endogenous ETV6 locus show expansion of the CD19−IL-7R+ compartment, show a partial block in B lineage commitment, and produce proB cells with aberrant myeloid gene expression signatures and potential: features (collectively) consistent with a pre-leukemic state.

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Section: Introductionmentioning

confidence: 99%

A Human IPS Model Implicates Embryonic B-Myeloid Fate Restriction as Developmental Susceptibility to B Acute Lymphoblastic Leukemia-Associated ETV6-RUNX1

et al. 2018

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“…The effect of Id1 in leukemogenesis seems largely dependent on p21. The expression of p21 is extremely low in human fetal hematopoietic stem/progenitor cells, but it increases as the cells differentiate into myeloid cells [46,47]. Conclusion was also gained by researchers that low expression of Id1 was observed in most AML cell lines and human AML samples [48].…”

Section: Leukemiamentioning

confidence: 94%

“…Study shows that mice receiving MLL-AF9-transduced fetal liver cells or bone marrow cells develop AML. Loss of Id1 significantly prolonged the median survival of mice receiving fetal liver cells but accelerated leukemogenesis in recipients of bone marrow cells [46]. The effect of Id1 in leukemogenesis seems largely dependent on p21.…”

Section: Leukemiamentioning

confidence: 98%

Inhibitor of Differentiation 1 (Id1) in Cancer and Cancer Therapy

Zhao

Gong

et al. 2020

Int. J. Med. Sci.

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The inhibitor of DNA binding (Id) proteins are regulators of cell cycle and cell differentiation. Of all Id family proteins, Id1 is mostly linked to tumorigenesis, cellular senescence as well as cell proliferation and survival. Id1 is a stem cell-like gene more than a classical oncogene. Id1 is overexpressed in numerous types of cancers and exerts its promotion effect to these tumors through different pathways. Briefly, Id1 was found significantly correlated with EMT-related proteins, K-Ras signaling, EGFR signaling, BMP signaling, PI3K/Akt signaling, WNT and SHH signaling, c-Myc signaling, STAT3 signaling, RK1/2 MAPK/Egr1 pathway and TGF-β pathway, etc. Id1 has potent effect on facilitating tumorous angiogenesis and metastasis. Moreover, high expression of Id1 plays a facilitating role in the development of drug resistance, including chemoresistance, radiation resistance and resistance to drugs targeting angiogenesis. However, controversial results were also obtained. Overall, Id1 represent a promising target of anti-tumor therapeutics based on its potent promotion effect to cancer. Numerous drugs were found exerting their anti-tumor function through Id1-related signaling pathways, such as fucoidan, berberine, tetramethylpyrazine, crizotinib, cannabidiol and vinblastine.

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“…However, despite intensive investigation of the intrinsic and extrinsic factors regulating HSPC biology and their relationship to leukemogenesis, this has not been achieved so far. Several studies showed that gene fusions recurrent in pediatric leukemias can lead to divergent outcomes in terms of disease aggressiveness, latency, phenotype, and transcriptional features, according to their time of appearance during ontogeny ( Chen W. et al, 2011 ; Horton et al, 2013 ; Man et al, 2016 ; Chaudhury et al, 2018 ; Lopez et al, 2019 ; Sinha et al, 2020 ). Differences in lineage specification and disease latency have been clearly shown after the induction of Mll-Af9 in FL and adult BM HSCs.…”

Section: Models For the Study Of The Origin Of Childhood Leukemiasmentioning

confidence: 99%

Prenatal Origin of Pediatric Leukemia: Lessons From Hematopoietic Development

Cazzola

Cazzaniga

Biondi

et al. 2021

Front. Cell Dev. Biol.

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Several lines of evidence suggest that childhood leukemia, the most common cancer in young age, originates during in utero development. However, our knowledge of the cellular origin of this large and heterogeneous group of malignancies is still incomplete. The identification and characterization of their cell of origin is of crucial importance in order to define the processes that initiate and sustain disease progression, to refine faithful animal models and to identify novel therapeutic approaches. During embryogenesis, hematopoiesis takes place at different anatomical sites in sequential waves, and occurs in both a hematopoietic stem cell (HSC)-dependent and a HSC-independent fashion. Despite the recently described relevance and complexity of HSC-independent hematopoiesis, few studies have so far investigated its potential involvement in leukemogenesis. Here, we review the current knowledge on prenatal origin of leukemias in the context of recent insights in developmental hematopoiesis.

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Differential role of Id1 in MLL-AF9–driven leukemia based on cell of origin

Abstract: Key Points

Cited by 14 publications

References 24 publications

A Human IPS Model Implicates Embryonic B-Myeloid Fate Restriction as Developmental Susceptibility to B Acute Lymphoblastic Leukemia-Associated ETV6-RUNX1

A Human IPS Model Implicates Embryonic B-Myeloid Fate Restriction as Developmental Susceptibility to B Acute Lymphoblastic Leukemia-Associated ETV6-RUNX1

Inhibitor of Differentiation 1 (Id1) in Cancer and Cancer Therapy

Prenatal Origin of Pediatric Leukemia: Lessons From Hematopoietic Development

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