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Acute Leukemias

Incidence and prognostic impact of c-Kit, FLT3, and Ras gene mutations in core binding factor acute myeloid leukemia (CBF-AML)

Leukemia volume 20, pages 965–970 (2006)Cite this article

Abstract

In core binding factors (CBF) acute myeloid leukemia (AML), the disruption of CBFα/β genes impairs normal hematopoietic differentiation and is supposed to cooperate with additional mutations promoting proliferation. The incidence and the prognosis of receptor tyrosine kinase (RTK) c-Kit and FLT3 mutations and Ras mutations were evaluated in 103 pediatric and adult patients with CBF-AML. c-Kit mutations were present in 17% patients. c-Kit exon 8 mutations were more frequent in inv(16) than in t(8;21) subset (20 versus 6%). Only one patient had FLT3-ITD but FLT3-D835 was as frequent as reported in AML population (7%). Ras mutations were significantly more frequent in inv(16) than in t(8;21) subset (36 versus 8%, P=0.001). RTK mutations were associated with a higher white blood cell count (WBC) (36 versus 21 G/L, P=0.05). FLT3 mutations were significantly associated with a shorter EFS and survival (P<0.0001 and P=0.0002) owing to an excess of early events. c-Kit mutations were associated with a shorter EFS and RFS (P=0.002 and P=0.003) in t(8;21) but not inv(16) patients. As previously observed, Ras mutations did not affect prognosis. Screening for RTK mutations may help to identify patients with a more adverse outcome and thus susceptible to benefit from intensified protocols or RTK inhibitors.

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Acknowledgements

This work was supported by the Canceropole Nord-ouest (Axe onco-hématologie) and by The STIC 2005.

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Authors and Affiliations

  1. Service d'Hématologie Adulte, Hôpital Saint-Louis, Paris, France

    N Boissel, E Raffoux & H Dombret

  2. Laboratoire d'Hématologie A, Hôpital Calmettes, Lille, France

    H Leroy, N Philippe & C Preudhomme

  3. Service d'Hématologie Pédiatrique, Hôpital Saint-Louis, Paris, France

    B Brethon, T Leblanc & A Baruchel

  4. Service des Maladies du Sang, CHU de Lille, Lille, France

    S de Botton & B Quesnel

  5. Service d'Onco-hématologie pédiatrique, Hôpital Trousseau, Paris, France

    A Auvrignon & G Leverger

  6. Service d'Hématologie Clinique, Hôpital Edouard Herriot, Lyon, France

    X Thomas

  7. Service d'Hématologie, Hôpital Necker, Paris, France

    O Hermine

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for the Acute Leukemia French Association (ALFA) and the Leucémies Aiguës Myéloblastiques de l'Enfant (LAME) Cooperative Groups

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Correspondence to C Preudhomme.

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Boissel, N., Leroy, H., Brethon, B. et al. Incidence and prognostic impact of c-Kit, FLT3, and Ras gene mutations in core binding factor acute myeloid leukemia (CBF-AML). Leukemia 20, 965–970 (2006). https://doi.org/10.1038/sj.leu.2404188

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