Leukemia-associated NF1 inactivation in patients with pediatric T-ALL and AML lacking evidence for neurofibromatosis
- Author
- Brian V Balgobind, Pieter Van Vlierberghe (UGent) , Ans MW van den Ouweland, H Berna Beverloo, Joan NR Terlouw-Kromosoeto, Elisabeth R van Wering, Dirk Reinhardt, Martin Horstmann, Gertjan JL Kaspers, Rob Pieters, C Michel Zwaan, Marry M Van den Heuvel-Eibrink and Jules PP Meijerink
- Organization
- Abstract
- Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder caused by mutations in the NF1 gene. Patients with NF1 have a higher risk to develop juvenile myelomonocytic leukemia (JMML) with a possible progression toward acute myeloid leukemia (AML). In an oligo array comparative genomic hybridization-based screening of 103 patients with pediatric T-cell acute lymphoblastic leukemia (T-ALL) and 71 patients with MLL-rearranged AML, a recurrent cryptic deletion, del(17)(q11.2), was identified in 3 patients with T-ALL and 2 patients with MLL-rearranged AML. This deletion has previously been described as a microdeletion of the NF1 region in patients with NF1. However, our patients lacked clinical NF1 symptoms. Mutation analysis in 4 of these del(17)(q11.2)-positive patients revealed that mutations in the remaining NF1 allele were present in 3 patients, confirming its role as a tumor-suppressor gene in cancer. In addition, NF1 inactivation was confirmed at the RNA expression level in 3 patients tested. Since the NF1 protein is a negative regulator of the RAS pathway (RAS-GTPase activating protein), homozygous NF1 inactivation represent a novel type I mutation in pediatric MLL-rearranged AML and T-ALL with a predicted frequency that is less than 10%. NF1 inactivation may provide an additional proliferative signal toward the development of leukemia.
- Keywords
- NUCLEOTIDE POLYMORPHISM ANALYSIS, ACUTE LYMPHOBLASTIC-LEUKEMIA, UNIPARENTAL DISOMY, SOMATIC RECOMBINATION, ACUTE MYELOID-LEUKEMIA, JUVENILE MYELOMONOCYTIC LEUKEMIA, MOLECULAR-GENETICS, TYPE-1, ACTIVATION, CHILDREN
Downloads
-
BLOOD 2008 VanVlierberghe.full.pdf
- full text
- |
- open access
- |
- |
- 753.29 KB
Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-5646968
- MLA
- Balgobind, Brian V., et al. “Leukemia-Associated NF1 Inactivation in Patients with Pediatric T-ALL and AML Lacking Evidence for Neurofibromatosis.” BLOOD, vol. 111, no. 8, 2008, pp. 4322–28, doi:10.1182/blood-2007-06-095075.
- APA
- Balgobind, B. V., Van Vlierberghe, P., van den Ouweland, A. M., Beverloo, H. B., Terlouw-Kromosoeto, J. N., van Wering, E. R., … Meijerink, J. P. (2008). Leukemia-associated NF1 inactivation in patients with pediatric T-ALL and AML lacking evidence for neurofibromatosis. BLOOD, 111(8), 4322–4328. https://doi.org/10.1182/blood-2007-06-095075
- Chicago author-date
- Balgobind, Brian V, Pieter Van Vlierberghe, Ans MW van den Ouweland, H Berna Beverloo, Joan NR Terlouw-Kromosoeto, Elisabeth R van Wering, Dirk Reinhardt, et al. 2008. “Leukemia-Associated NF1 Inactivation in Patients with Pediatric T-ALL and AML Lacking Evidence for Neurofibromatosis.” BLOOD 111 (8): 4322–28. https://doi.org/10.1182/blood-2007-06-095075.
- Chicago author-date (all authors)
- Balgobind, Brian V, Pieter Van Vlierberghe, Ans MW van den Ouweland, H Berna Beverloo, Joan NR Terlouw-Kromosoeto, Elisabeth R van Wering, Dirk Reinhardt, Martin Horstmann, Gertjan JL Kaspers, Rob Pieters, C Michel Zwaan, Marry M Van den Heuvel-Eibrink, and Jules PP Meijerink. 2008. “Leukemia-Associated NF1 Inactivation in Patients with Pediatric T-ALL and AML Lacking Evidence for Neurofibromatosis.” BLOOD 111 (8): 4322–4328. doi:10.1182/blood-2007-06-095075.
- Vancouver
- 1.Balgobind BV, Van Vlierberghe P, van den Ouweland AM, Beverloo HB, Terlouw-Kromosoeto JN, van Wering ER, et al. Leukemia-associated NF1 inactivation in patients with pediatric T-ALL and AML lacking evidence for neurofibromatosis. BLOOD. 2008;111(8):4322–8.
- IEEE
- [1]B. V. Balgobind et al., “Leukemia-associated NF1 inactivation in patients with pediatric T-ALL and AML lacking evidence for neurofibromatosis,” BLOOD, vol. 111, no. 8, pp. 4322–4328, 2008.
@article{5646968, abstract = {{Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder caused by mutations in the NF1 gene. Patients with NF1 have a higher risk to develop juvenile myelomonocytic leukemia (JMML) with a possible progression toward acute myeloid leukemia (AML). In an oligo array comparative genomic hybridization-based screening of 103 patients with pediatric T-cell acute lymphoblastic leukemia (T-ALL) and 71 patients with MLL-rearranged AML, a recurrent cryptic deletion, del(17)(q11.2), was identified in 3 patients with T-ALL and 2 patients with MLL-rearranged AML. This deletion has previously been described as a microdeletion of the NF1 region in patients with NF1. However, our patients lacked clinical NF1 symptoms. Mutation analysis in 4 of these del(17)(q11.2)-positive patients revealed that mutations in the remaining NF1 allele were present in 3 patients, confirming its role as a tumor-suppressor gene in cancer. In addition, NF1 inactivation was confirmed at the RNA expression level in 3 patients tested. Since the NF1 protein is a negative regulator of the RAS pathway (RAS-GTPase activating protein), homozygous NF1 inactivation represent a novel type I mutation in pediatric MLL-rearranged AML and T-ALL with a predicted frequency that is less than 10%. NF1 inactivation may provide an additional proliferative signal toward the development of leukemia.}}, author = {{Balgobind, Brian V and Van Vlierberghe, Pieter and van den Ouweland, Ans MW and Beverloo, H Berna and Terlouw-Kromosoeto, Joan NR and van Wering, Elisabeth R and Reinhardt, Dirk and Horstmann, Martin and Kaspers, Gertjan JL and Pieters, Rob and Zwaan, C Michel and Van den Heuvel-Eibrink, Marry M and Meijerink, Jules PP}}, issn = {{0006-4971}}, journal = {{BLOOD}}, keywords = {{NUCLEOTIDE POLYMORPHISM ANALYSIS,ACUTE LYMPHOBLASTIC-LEUKEMIA,UNIPARENTAL DISOMY,SOMATIC RECOMBINATION,ACUTE MYELOID-LEUKEMIA,JUVENILE MYELOMONOCYTIC LEUKEMIA,MOLECULAR-GENETICS,TYPE-1,ACTIVATION,CHILDREN}}, language = {{eng}}, number = {{8}}, pages = {{4322--4328}}, title = {{Leukemia-associated NF1 inactivation in patients with pediatric T-ALL and AML lacking evidence for neurofibromatosis}}, url = {{http://doi.org/10.1182/blood-2007-06-095075}}, volume = {{111}}, year = {{2008}}, }
- Altmetric
- View in Altmetric
- Web of Science
- Times cited: