Development of embryonic and adult leukemia mouse models driven by MLL-ENL translocation

Sinha, Roshani; Porcheri, Cristina; D’Altri, Teresa; González, Jéssica; Ruiz-Herguido, Cristina; Rabbitts, Terry; Espinosa, Lluís; Bigas, Anna

doi:10.1016/j.exphem.2020.04.008

Cited by 8 publications

(12 citation statements)

References 24 publications

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“…We, and others, have previously reported that pediatric leukemia driver mutations have different effects on HSC and HPC fates at different ages [58,105−110]. For example, the MLL −ENL fusion protein induces acute myeloid leukemia more efficiently during neonatal stages of development than during fetal or adult stages [106,111]. The CBFA2T3−GLIS2 fusion similarly transforms fetal HSCs/HPCs more efficiently than adult HSCs/HPCs [107].…”

Section: Neonatal Hsc/hpc Ontogeny and Childhood Leukemia Initiationmentioning

confidence: 99%

Transcriptional reprogramming in neonatal hematopoietic stem and progenitor cells

Magee

2021

Experimental Hematology

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Section: Neonatal Hsc/hpc Ontogeny and Childhood Leukemia Initiationmentioning

confidence: 99%

Transcriptional reprogramming in neonatal hematopoietic stem and progenitor cells

Magee

2021

Experimental Hematology

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“…The induction of the Mll-Enl translocation in FL HSPCs at E12.5 led to an overt, more aggressive AML form than the one triggered in adults, and to a transplantable disease in secondary recipients (Sinha et al, 2020). Overall, these studies suggested that childhood leukemias originating from the FL possess unique features that differentiate them from the ones resulting from the same genetic lesions occurring in the adult.…”

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

confidence: 84%

“…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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“…This observation suggests that infant and adult leukemias are biologically distinct but the underlying molecular mechanisms for these differences are not understood. Sinha et al have developed a novel MLL-ENL embryonic leukemia model in mice that can be used to study some aspects of infant leukemia ontogeny [35].…”

Section: Discussionmentioning

confidence: 99%

Exome sequencing of glioblastoma-derived cancer stem cells reveals rare clinically relevant frameshift deletion in MLLT1 gene

et al. 2022

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Background Glioblastoma multiforme (GBM) is a heterogeneous CNS neoplasm which causes significant morbidity and mortality. One reason for the poor prognostic outcome of GBM is attributed to the presence of cancer stem cells (CSC) which confer resistance against standard chemo- and radiotherapeutics modalities. Two types of GBM-associated CSC were isolated from the same patient: tumor core- (c-CSC) and peritumor tissue-derived cancer stem cells (p-CSC). Our experiments are focused on glioblastoma–IDH-wild type, and no disease-defining alterations were present in histone, BRAF or other genes. Methods In the present study, potential differences in genetic variants between c-CSC versus p-CSC derived from four GBM patients were investigated with the aims of (1) comparing the exome sequences between all the c-CSC or p-CSC to identify the common variants; (2) identifying the variants affecting the function of genes known to be involved in cancer origin and development. Results By comparative analyses, we identified common gene single nucleotide variants (SNV) in all GBM c-CSC and p-CSC, a potentially deleterious variant was a frameshift deletion at Gln461fs in the MLLT1 gene, that was encountered only in p-CSC samples with different allelic frequency. Conclusions We discovered a potentially harmful frameshift deletion at Gln461fs in the MLLT1 gene. Further investigation is required to confirm the presence of the identified mutations in patient tissue samples, as well as the significance of the frameshift mutation in the MLLT1 gene on GBM biology and response to therapy based on genomic functional experiments.

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Development of embryonic and adult leukemia mouse models driven by MLL-ENL translocation

Cited by 8 publications

References 24 publications

Transcriptional reprogramming in neonatal hematopoietic stem and progenitor cells

Transcriptional reprogramming in neonatal hematopoietic stem and progenitor cells

Prenatal Origin of Pediatric Leukemia: Lessons From Hematopoietic Development

Exome sequencing of glioblastoma-derived cancer stem cells reveals rare clinically relevant frameshift deletion in MLLT1 gene

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