Activating FLT3 mutations are rare in children with juvenile myelomonocytic leukemia

Pediatric Blood & Cancer
Eric J GratiasPeter D Emanuel

Abstract

Activating mutations of FLT3 have been identified in multiple myeloid malignancies. Two types of activating mutations have been described: (1) the internal tandem duplication (FLT3-ITD) and (2) point mutations within the activating loop (FLT3-ALM). Juvenile myelomonocytic leukemia (JMML) is a rare myelodysplastic/myeloproliferative disorder of early childhood. Mutations and other genetic abnormalities of RAS, NF1, and PTPN11 have been implicated as causative events in JMML, but approximately 25% of JMML patients harbor none of these abnormalities. We investigated whether FLT3 mutations might also contribute to JMML pathogenesis, and if present, whether FLT3 status would correlate with disease natural history and prognosis. Genomic DNA was isolated from peripheral blood and bone marrow samples of 60 patients meeting international JMML diagnostic criteria. Samples were analyzed for FLT3-ITD and FLT3-ALM using polymerase chain reaction and restriction endonuclease digestion. FLT3-ALM was found in 1/60 (1.7%) patients analyzed. Direct sequencing confirmed a C836G mutation. Clinical and laboratory characteristics of the JMML patient with the FLT3-ALM did not differ from the remainder of the cohort. No FLT3-ITD mutations were detecte...Continue Reading

References

Feb 11, 1988·Nucleic Acids Research·S A MillerH F Polesky
Jul 10, 2001·British Journal of Haematology·F M Abu-DuhierJ T Reilly
Dec 3, 2003·Blood·Mignon L LohKevin M Shannon

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Citations

Sep 7, 2007·Journal of Pediatric Hematology/oncology·Akira ShimadaYasuhide Hayashi
Feb 9, 2010·Haematologica·Andrica C H de VriesMarry M van den Heuvel-Eibrink
Dec 14, 2011·Advances in Hematology·Xiaoling LiuCheng-Kui Qu
Apr 14, 2006·Mayo Clinic Proceedings·Ayalew TefferiAnimesh Pardanani
May 17, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Mignon L Loh, Charles G Mullighan
Jan 26, 2020·Blood Reviews·Sonia Meynier, Frédéric Rieux-Laucat

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