The DOI matches its Crossref record; 73 of the 73 references it cites were found in a registry or an index.
FLT3-ITD Knockin Impairs Hematopoietic Stem Cell Quiescence/Homeostasis, Leading to Myeloproliferative Neoplasm
Abstract
SUMMARY Internal tandem duplication (ITD) mutations within the FMS-Like Tyrosine Kinase gene (FLT3) render the receptor constitutively active, driving proliferation and survival in leukemic blasts. Expression of Flt3-ITD from the endogenous promoter in a murine knock-in model results in progenitor expansion and a myeloproliferative neoplasm. In this study, we show that this expansion begins with over-proliferation within a compartment of normally quiescent long-term hematopoietic stem cells (LT-HSCs), which become rapidly depleted. This depletion is reversible upon treatment with the small molecule inhibitor Sorafenib, which also ablates the disease. Although the normal LT-HSC has been defined as Flt3-negative by flow cytometric detection, we demonstrate that Flt3 is capable of playing a role within this compartment by examining the effects of constitutively activated Flt3-ITD. This indicates an important link between stem cell quiescence/homeostasis and myeloproliferative disease while also giving novel insight into the emergence of FLT3-ITD mutations in the evolution of leukemic transformation.
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“Older mice carrying loss of function alleles in Tet2 or Dnmt3a manifest an expanded HSPC pool, including a hematopoietic stem cell (HSC)-enriched fraction defined by cell surface markers Lineage-/Sca-1+/c-Kit+ (LSK).”
From Inhibition of Inflammatory Signaling in Tet2 Mutant Preleukemic Cells Mitigates Stress-Induced Abnormalities and Clonal Hematopoiesis (2018) · cites this paper as Chu et al., 2012
Experimental — accuracy not yet measuredIn the citing paper
“Some of these genetically modified mice go on to develop CMML or MPN with modest penetration when aged (Challen et al., 2012; Chu et al., 2012; Ko et al., 2011; Li et al., 2011; Moran-Crusio et al., 2011; Quivoron et al., 2011).”
From Inhibition of Inflammatory Signaling in Tet2 Mutant Preleukemic Cells Mitigates Stress-Induced Abnormalities and Clonal Hematopoiesis (2018) · cites this paper as Chu et al., 2012
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Citations
Cites
Sorafenib in Advanced Clear-Cell Renal-Cell Carcinoma
Escudier, B., Eisen, T., Stadler, W. M., Szczylik, C., Oudard, S., Siebels, M., Negrier, S., Chevreau, C., Solska, E., Desai, A. A., et al. (2007) · New England Journal of Medicine · doi:10.1056/nejmoa060655 · Cited by 4,802
A cell initiating human acute myeloid leukaemia after transplantation into SCID mice
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Purification and Characterization of Mouse Hematopoietic Stem Cells
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Long-Term Lymphohematopoietic Reconstitution by a Single CD34-Low/Negative Hematopoietic Stem Cell
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The roles of FLT3 in hematopoiesis and leukemia
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Kottaridis, P. D., Gale, R. E., Frew, M. E., Harrison, G., Langabeer, S. E., Belton, A. A., Walker, H., Wheatley, K., Bowen, D. T., Burnett, A. K., et al. (2001) · Blood · doi:10.1182/blood.v98.6.1752 · Cited by 1,551
Internal tandem duplication of the flt3 gene found in acute myeloid leukemia.
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Cited by
Cai, Z., Kotzin, J. J., Ramdas, B., Chen, S., Nelanuthala, S., Palam, L. R., Pandey, R., Mali, R. S., Liu, Y., Kelley, M. R., et al. (2018) · Cell Stem Cell · doi:10.1016/j.stem.2018.10.013 · Cited by 394
Li, L., Osdal, T., Ho, Y., Chun, S., McDonald, T., Agarwal, P., Lin, A., Chu, S., Qi, J., Li, L., et al. (2014) · Cell stem cell · doi:10.1016/j.stem.2014.08.001 · Cited by 234
Self-citationShih, A. H., Jiang, Y., Meydan, C., Shank, K., Pandey, S., Barreyro, L., Antony-Debre, I., Viale, A., Socci, N., Sun, Y., et al. (2015) · Cancer Cell · doi:10.1016/j.ccell.2015.03.009 · Cited by 236
“This is in contrast to reported FLT3 inhibition in Flt3ITD mice where aberrant differentiation is effectively reversed (Chu et al., 2012).”
ResultOgawara, Y., Katsumoto, T., Aikawa, Y., Shima, Y., Kagiyama, Y., Soga, T., Matsunaga, H., Seki, T., Araki, K., & Kitabayashi, I. (2015) · Cancer Research · doi:10.1158/0008-5472.can-14-2200 · Cited by 58
Pawar, A. S., Somers, P., Alex, A., Grana, J., Feist, V. K., George, S. S., Jalnapurkar, S. S., Antony, C., Verner, R., White-Brown, S. K., et al. (2025) · Genes & Development · doi:10.1101/gad.352602.125 · Cited by 3
Metadata
- Authors
- Chu, S. H., Heiser, D., Li, L., Kaplan, I., Collector, M., Huso, D., Sharkis, S. J., Civin, C., & Small, D.
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2012-09
- Volume
- 11
- Issue
- 3
- Pages
- 346-358
- ISSN
- 1934-5909
- PMC
- PMC3725984
- Cited by
- 79
- References
- 73
- Language
- en
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 374 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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