Lack of CD45 in FLT3-ITD mice results in a myeloproliferative phenotype, cortical porosity, and ectopic bone formation

Oncogene
Anne KresinskyJörg P Müller

Abstract

The receptor tyrosine kinase FLT3 is expressed in myeloid and lymphoid progenitor cells. Activating mutations in FLT3 occur in 25-30% of acute myeloid leukaemia (AML) patients. Most common are internal tandem duplications of sequence (ITD) leading to constitutive FLT3-ITD kinase activity with an altered signalling quality promoting leukaemic cell transformation. Here, we observed the attenuating role of the receptor-like protein tyrosine phosphatase (RPTP) CD45/Ptprc in FLT3 signalling in vivo. Low level expression of this abundant RPTP correlates with a poor prognosis of FLT3-ITD-positive AML patients. To get a further insight into the regulatory role of Ptprc in FLT3-ITD activity in vivo, Ptprc knock-out mice were bred with FLT3-ITD knock-in mice. Inactivation of the Ptprc gene in FLT3-ITD mice resulted in a drastically shortened life span and development of severe monocytosis, a block in B-cell development and anaemia. The myeloproliferative phenotype was associated with extramedullary haematopoiesis, splenohepatomegaly and severe alterations of organ structures. The phenotypic alterations were associated with increased transforming signalling of FLT3-ITD, including activation of its downstream target STAT5. These data revea...Continue Reading

References

Aug 8, 1998·Seminars in Immunology·A L DeFrancoC A Lowell
Feb 23, 1999·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·P R EbelingA P Grigg
Aug 6, 2000·Osteoporosis International : a Journal Established As Result of Cooperation Between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA·C SchulteK Mann
Aug 15, 2002·Blood·D Gary Gilliland, James D Griffin
Sep 3, 2003·Nature Reviews. Cancer·Derek L Stirewalt, Jerald P Radich
Jun 10, 2004·Cell·Andres AlonsoTomas Mustelin
Apr 16, 2005·Molecular and Cellular Biology·Dirk-E Schmidt-ArrasFrank-D Böhmer
Mar 25, 2006·Nature Reviews. Cancer·Arne OstmanFrank D Böhmer
Nov 3, 2006·Leukemia Research·Ronald Feitosa PinheiroMaria de Lourdes L F Chauffaille
Aug 19, 2007·Cell·Na Kyung LeeGerard Karsenty
Oct 27, 2009·Molecular Cell·Chunaram ChoudharyHubert Serve
Jan 26, 2011·The Journal of Biological Chemistry·Deepika AroraJörg P Müller
Jun 12, 2012·The FEBS Journal·Frank BöhmerJeroen den Hertog
May 28, 2013·Biochimica Et Biophysica Acta·Wiljan J A J Hendriks, Rafael Pulido
Mar 5, 2016·Journal of Leukocyte Biology·Irina Voronov, Morris F Manolson
Jun 9, 2016·The New England Journal of Medicine·Elli PapaemmanuilPeter J Campbell

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Citations

Oct 3, 2020·Cancers·Jörg P Müller, Dirk Schmidt-Arras
May 28, 2021·Journal of Clinical Pathology·Maryam Ahmed Al BarashdiKen Mills

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Datasets Mentioned

BETA
GPL570

Methods Mentioned

BETA
profiler
dot blot
fluorescence-activated cell sorting
flow cytometry
transgenic
electrophoresis

Software Mentioned

SigmaPlot
Survival Analysis
R

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