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Deciphering KRAS and NRAS mutated clone dynamics in MLL-AF4 paediatric leukaemia by ultra deep sequencing analysis
by
Giarin, Emanuela
, Bresolin, Silvia
, Basso, Giuseppe
, Fais, Franco
, Trentin, Luca
, Accordi, Benedetta
, Serafin, Valentina
, Kronnie, Geertruy te
, Tenca, Claudya
, De Lorenzo, Paola
, Cazzaniga, Giovanni
, Valsecchi, Maria Grazia
, Bardini, Michela
in
38
/ 38/61
/ 45/47
/ 631/67/1990/283/2125
/ 692/4017
/ 82
/ 82/79
/ Acute lymphoblastic leukemia
/ AF4 protein
/ Cloning
/ Female
/ Fusion protein
/ GTP Phosphohydrolases - genetics
/ GTP Phosphohydrolases - metabolism
/ High-Throughput Nucleotide Sequencing
/ Humanities and Social Sciences
/ Humans
/ K-Ras protein
/ Leukemia
/ Leukemia - genetics
/ Leukemia - metabolism
/ Leukemia - pathology
/ Lymphocytes B
/ Male
/ Membrane Proteins - genetics
/ Membrane Proteins - metabolism
/ multidisciplinary
/ Mutation
/ Myeloid-Lymphoid Leukemia Protein
/ Oncogene Proteins, Fusion
/ Proto-Oncogene Proteins p21(ras) - genetics
/ Proto-Oncogene Proteins p21(ras) - metabolism
/ Science
/ Transcription
2016
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Deciphering KRAS and NRAS mutated clone dynamics in MLL-AF4 paediatric leukaemia by ultra deep sequencing analysis
by
Giarin, Emanuela
, Bresolin, Silvia
, Basso, Giuseppe
, Fais, Franco
, Trentin, Luca
, Accordi, Benedetta
, Serafin, Valentina
, Kronnie, Geertruy te
, Tenca, Claudya
, De Lorenzo, Paola
, Cazzaniga, Giovanni
, Valsecchi, Maria Grazia
, Bardini, Michela
in
38
/ 38/61
/ 45/47
/ 631/67/1990/283/2125
/ 692/4017
/ 82
/ 82/79
/ Acute lymphoblastic leukemia
/ AF4 protein
/ Cloning
/ Female
/ Fusion protein
/ GTP Phosphohydrolases - genetics
/ GTP Phosphohydrolases - metabolism
/ High-Throughput Nucleotide Sequencing
/ Humanities and Social Sciences
/ Humans
/ K-Ras protein
/ Leukemia
/ Leukemia - genetics
/ Leukemia - metabolism
/ Leukemia - pathology
/ Lymphocytes B
/ Male
/ Membrane Proteins - genetics
/ Membrane Proteins - metabolism
/ multidisciplinary
/ Mutation
/ Myeloid-Lymphoid Leukemia Protein
/ Oncogene Proteins, Fusion
/ Proto-Oncogene Proteins p21(ras) - genetics
/ Proto-Oncogene Proteins p21(ras) - metabolism
/ Science
/ Transcription
2016
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Deciphering KRAS and NRAS mutated clone dynamics in MLL-AF4 paediatric leukaemia by ultra deep sequencing analysis
by
Giarin, Emanuela
, Bresolin, Silvia
, Basso, Giuseppe
, Fais, Franco
, Trentin, Luca
, Accordi, Benedetta
, Serafin, Valentina
, Kronnie, Geertruy te
, Tenca, Claudya
, De Lorenzo, Paola
, Cazzaniga, Giovanni
, Valsecchi, Maria Grazia
, Bardini, Michela
in
38
/ 38/61
/ 45/47
/ 631/67/1990/283/2125
/ 692/4017
/ 82
/ 82/79
/ Acute lymphoblastic leukemia
/ AF4 protein
/ Cloning
/ Female
/ Fusion protein
/ GTP Phosphohydrolases - genetics
/ GTP Phosphohydrolases - metabolism
/ High-Throughput Nucleotide Sequencing
/ Humanities and Social Sciences
/ Humans
/ K-Ras protein
/ Leukemia
/ Leukemia - genetics
/ Leukemia - metabolism
/ Leukemia - pathology
/ Lymphocytes B
/ Male
/ Membrane Proteins - genetics
/ Membrane Proteins - metabolism
/ multidisciplinary
/ Mutation
/ Myeloid-Lymphoid Leukemia Protein
/ Oncogene Proteins, Fusion
/ Proto-Oncogene Proteins p21(ras) - genetics
/ Proto-Oncogene Proteins p21(ras) - metabolism
/ Science
/ Transcription
2016
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Deciphering KRAS and NRAS mutated clone dynamics in MLL-AF4 paediatric leukaemia by ultra deep sequencing analysis
Journal Article
Deciphering KRAS and NRAS mutated clone dynamics in MLL-AF4 paediatric leukaemia by ultra deep sequencing analysis
2016
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Overview
To induce and sustain the leukaemogenic process, MLL-AF4+ leukaemia seems to require very few genetic alterations in addition to the fusion gene itself. Studies of infant and paediatric patients with MLL-AF4+ B cell precursor acute lymphoblastic leukaemia (BCP-ALL) have reported mutations in
KRAS
and
NRAS
with incidences ranging from 25 to 50%. Whereas previous studies employed Sanger sequencing, here we used next generation amplicon deep sequencing for in depth evaluation of
RAS
mutations in 36 paediatric patients at diagnosis of MLL-AF4+ leukaemia.
RAS
mutations including those in small sub-clones were detected in 63.9% of patients. Furthermore, the mutational analysis of 17 paired samples at diagnosis and relapse revealed complex RAS clone dynamics and showed that the mutated clones present at relapse were almost all originated from clones that were already detectable at diagnosis and survived to the initial therapy. Finally, we showed that mutated patients were indeed characterized by a
RAS
related signature at both transcriptional and protein levels and that the targeting of the RAS pathway could be of beneficial for treatment of MLL-AF4+ BCP-ALL clones carrying somatic
RAS
mutations.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 38/61
/ 45/47
/ 692/4017
/ 82
/ 82/79
/ Acute lymphoblastic leukemia
/ Cloning
/ Female
/ GTP Phosphohydrolases - genetics
/ GTP Phosphohydrolases - metabolism
/ High-Throughput Nucleotide Sequencing
/ Humanities and Social Sciences
/ Humans
/ Leukemia
/ Male
/ Membrane Proteins - genetics
/ Membrane Proteins - metabolism
/ Mutation
/ Myeloid-Lymphoid Leukemia Protein
/ Proto-Oncogene Proteins p21(ras) - genetics
/ Proto-Oncogene Proteins p21(ras) - metabolism
/ Science
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