Leukemia-associated NF1 inactivation in patients with pediatric T-ALL and AML lacking evidence for neurofibromatosis.
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Leukemia-associated NF1 inactivation in patients with pediatric T-ALL and AML lacking evidence for neurofibromatosis. / Balgobind, [Unbekannt]; Brian, V; Vlierberghe, Van; Pieter, [Unbekannt]; van Den, Ouweland; Ans, M W; Beverloo, [Unbekannt]; Berna, H; Terlouw-Kromosoeto, [Unbekannt]; Joan, N R; Wering, van; Elisabeth, R; Reinhardt, [Unbekannt]; Dirk, [Unbekannt]; Horstmann, Martin; Martin, [Unbekannt]; Kaspers, [Unbekannt]; Gertjan, J L; Pieters, [Unbekannt]; Rob, [Unbekannt]; Zwaan, [Unbekannt]; Michel, C; Heuvel-Eibrink, Van Den; Marry, M; Meijerink, [Unbekannt]; Jules, P P.
in: BLOOD, Jahrgang 111, Nr. 8, 8, 2008, S. 4322-4328.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Leukemia-associated NF1 inactivation in patients with pediatric T-ALL and AML lacking evidence for neurofibromatosis.
AU - Balgobind, [Unbekannt]
AU - Brian, V
AU - Vlierberghe, Van
AU - Pieter, [Unbekannt]
AU - van Den, Ouweland
AU - Ans, M W
AU - Beverloo, [Unbekannt]
AU - Berna, H
AU - Terlouw-Kromosoeto, [Unbekannt]
AU - Joan, N R
AU - Wering, van
AU - Elisabeth, R
AU - Reinhardt, [Unbekannt]
AU - Dirk, [Unbekannt]
AU - Horstmann, Martin
AU - Martin, [Unbekannt]
AU - Kaspers, [Unbekannt]
AU - Gertjan, J L
AU - Pieters, [Unbekannt]
AU - Rob, [Unbekannt]
AU - Zwaan, [Unbekannt]
AU - Michel, C
AU - Heuvel-Eibrink, Van Den
AU - Marry, M
AU - Meijerink, [Unbekannt]
AU - Jules, P P
PY - 2008
Y1 - 2008
N2 - 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.
AB - 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.
M3 - SCORING: Zeitschriftenaufsatz
VL - 111
SP - 4322
EP - 4328
JO - BLOOD
JF - BLOOD
SN - 0006-4971
IS - 8
M1 - 8
ER -