Mutations in CBL occur frequently in juvenile myelomonocytic leukemia

Mignon L. Loh; Debbie S. Sakai; Christian Flotho; Michelle Kang; Manfred Fliegauf; Sophie Archambeault; Charles G. Mullighan; Leslie Chen; Eva Bergstraesser; Carlos E. Bueso-Ramos; Peter D. Emanuel; Henrik Hasle; Jean Pierre Issa; Marry M. Van Den Heuvel-Eibrink; Franco Locatelli; Jan Starý; Monica Trebo; Marcin Wlodarski; Marco Zecca; Kevin M. Shannon; Charlotte M. Niemeyer

doi:10.1182/blood-2009-01-198416

Mutations in CBL occur frequently in juvenile myelomonocytic leukemia

Mignon L. Loh, Debbie S. Sakai, Christian Flotho, Michelle Kang, Manfred Fliegauf, Sophie Archambeault, Charles G. Mullighan, Leslie Chen, Eva Bergstraesser, Carlos E. Bueso-Ramos, Peter D. Emanuel, Henrik Hasle, Jean Pierre Issa, Marry M. Van Den Heuvel-Eibrink, Franco Locatelli, Jan Starý, Monica Trebo, Marcin Wlodarski, Marco Zecca, Kevin M. ShannonCharlotte M. Niemeyer

Hematopathology

Research output: Contribution to journal › Article › peer-review

237 Scopus citations

Abstract

Juvenile myelomonocytic leukemia is an aggressive myeloproliferative disorder characterized by malignant transformation in the hematopoietic stem cell compartment with proliferation of differentiated progeny. Seventy-five percent of patients harbor mutations in the NF1, NRAS, KRAS, or PTPN11 genes, which encode components of Ras signaling networks. Using single nucleotide polymorphism arrays, we identified a region of 11q isodisomy that contains the CBL gene in several JMML samples, and subsequently identified CBL mutations in 27 of 159 JMML samples. Thirteen of these mutations alter codon Y371. In this report, we also demonstrate that CBL and RAS/PTPN11 mutations were mutually exclusive in these patients. Moreover, the exclusivity of CBL mutations with respect to other Ras pathway-associated mutations indicates that CBL may have a role in deregulating this key pathway in JMML.

Original language	English (US)
Pages (from-to)	1859-1863
Number of pages	5
Journal	Blood
Volume	114
Issue number	9
DOIs	https://doi.org/10.1182/blood-2009-01-198416
State	Published - 2009

ASJC Scopus subject areas

Biochemistry
Immunology
Hematology
Cell Biology

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Loh, M. L., Sakai, D. S., Flotho, C., Kang, M., Fliegauf, M., Archambeault, S., Mullighan, C. G., Chen, L., Bergstraesser, E., Bueso-Ramos, C. E., Emanuel, P. D., Hasle, H., Issa, J. P., Van Den Heuvel-Eibrink, M. M., Locatelli, F., Starý, J., Trebo, M., Wlodarski, M., Zecca, M., ... Niemeyer, C. M. (2009). Mutations in CBL occur frequently in juvenile myelomonocytic leukemia. Blood, 114(9), 1859-1863. https://doi.org/10.1182/blood-2009-01-198416

Loh, ML, Sakai, DS, Flotho, C, Kang, M, Fliegauf, M, Archambeault, S, Mullighan, CG, Chen, L, Bergstraesser, E, Bueso-Ramos, CE, Emanuel, PD, Hasle, H, Issa, JP, Van Den Heuvel-Eibrink, MM, Locatelli, F, Starý, J, Trebo, M, Wlodarski, M, Zecca, M, Shannon, KM & Niemeyer, CM 2009, 'Mutations in CBL occur frequently in juvenile myelomonocytic leukemia', Blood, vol. 114, no. 9, pp. 1859-1863. https://doi.org/10.1182/blood-2009-01-198416

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title = "Mutations in CBL occur frequently in juvenile myelomonocytic leukemia",

abstract = "Juvenile myelomonocytic leukemia is an aggressive myeloproliferative disorder characterized by malignant transformation in the hematopoietic stem cell compartment with proliferation of differentiated progeny. Seventy-five percent of patients harbor mutations in the NF1, NRAS, KRAS, or PTPN11 genes, which encode components of Ras signaling networks. Using single nucleotide polymorphism arrays, we identified a region of 11q isodisomy that contains the CBL gene in several JMML samples, and subsequently identified CBL mutations in 27 of 159 JMML samples. Thirteen of these mutations alter codon Y371. In this report, we also demonstrate that CBL and RAS/PTPN11 mutations were mutually exclusive in these patients. Moreover, the exclusivity of CBL mutations with respect to other Ras pathway-associated mutations indicates that CBL may have a role in deregulating this key pathway in JMML.",

author = "Loh, {Mignon L.} and Sakai, {Debbie S.} and Christian Flotho and Michelle Kang and Manfred Fliegauf and Sophie Archambeault and Mullighan, {Charles G.} and Leslie Chen and Eva Bergstraesser and Bueso-Ramos, {Carlos E.} and Emanuel, {Peter D.} and Henrik Hasle and Issa, {Jean Pierre} and {Van Den Heuvel-Eibrink}, {Marry M.} and Franco Locatelli and Jan Star{\'y} and Monica Trebo and Marcin Wlodarski and Marco Zecca and Shannon, {Kevin M.} and Niemeyer, {Charlotte M.}",

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AU - Fliegauf, Manfred

AU - Archambeault, Sophie

AU - Mullighan, Charles G.

AU - Chen, Leslie

AU - Bergstraesser, Eva

AU - Bueso-Ramos, Carlos E.

AU - Emanuel, Peter D.

AU - Hasle, Henrik

AU - Issa, Jean Pierre

AU - Van Den Heuvel-Eibrink, Marry M.

AU - Locatelli, Franco

AU - Starý, Jan

AU - Trebo, Monica

AU - Wlodarski, Marcin

AU - Zecca, Marco

AU - Shannon, Kevin M.

AU - Niemeyer, Charlotte M.

PY - 2009

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Mutations in CBL occur frequently in juvenile myelomonocytic leukemia

Abstract

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