EGAGenomicsExome Sequencinghttps://ega-archive.org/studies/EGAS00001006187EGAEGA study EGAS00001006187Exome sequencing from a child with neurofibromatosis and relapsed refractory acute lymphoblastic leukaemiaEGArestrictedneurofibromatosis type 4, cHILD, "Neurofibromatosis" EXACT [ICD9CM_2006:237.7], "Neurofibromatosis" EXACT [SNOMEDCT_2005_07_31:154642000], young adult, pediatric interstitial lung disease, Predictive Medicine, Multiple Neurofibroma, Individualized Medicine, Progress Reports, "neurofibromatosis" EXACT [CSP2005:2012-7338]., "Neurofibromatosis" EXACT [NCI2004_11_17:C6727], Personalized, neurofibromatosis, neurofibromatosis type 1 microdeletion syndrome, Investigative, Investigative Report, Personalized Medicine, Summary Report, type I, CHILD, Recklinghausen's disease, Research Reports, Precision, Neurofibromatosis, Neurofibromatosis 3, interstitial lung disease of childhood, Summary Reports, peripheral type, child, Neurofibromatosis Syndromes, Neurofibromatosis 3s, Neurofibromatosis Type 3s, neurofibromatosis type IV, Individualized, Progress Report, ILD specific to childhood, Neurofibromatosis Syndrome, Field, chILD syndrome, type 1 neurofibromatosis, Von Recklinghausen disease, Theranostic, Type 3, Neurofibromas, Children, paediatric interstitial lung disease, chILD, Progress, juvenile stage, Multiple, Report, Field Reports, "Neurofibromatosis syndrome (disorder)" EXACT [SNOMEDCT_2005_07_31:19133005], Syndromes, Reports, P-Health, children's interstitial lung disease, Theranostics, childhood interstitial lung disease, Syndrome, Medicine, P Health, Multiple Neurofibromas, Predictive, Investigative Reports, Summary, Neurofibromatosis Type 3, neurofibromatosis type 2, von Reklinghausen disease, Field Report, "Neurofibromatosis (morphologic abnormality)" EXACT [SNOMEDCT_2005_07_31:81669005], NeurofibromaKinase Kinases, Ras1/RAs85D, B Cells, RAS, Ras, l(1)G0098, precursor lymphoblastic lymphoma/leukemia, DSORT, "Neurofibromatosis" EXACT [ICD9CM_2006:237.7], dsor1, MAP-ERK Kinase, JTP74057, Bursa-Dependent Lymphocytes, Individualized Medicine, B cell, B acute lymphoblastic leukaemia, D-MEK/Dsor, c-rasHa, E(sev)3C, MEK1/2, Ras-1, PRKMK7, B-cell lymphoblastic leukaemia, CG11485, PD325901, Mutations, Relative, DmelCG8318, ras, relapse, c-ras2, type I, Su(Raf)34B, Kinase, Relapses, Neurofibromatosis, D-Ras1, peripheral type, Neurofibromatosis Syndromes, increased, B-cell acute lymphoblastic leukaemia, RTK, E030030H24Rik, MAPK-ERK Kinases, acute B-cell lymphocytic leukemia, trametinibum, l(1)G0436, Recurrences, type 1 neurofibromatosis, ras85B, ras85D, DSor1, DSOR1, B-cell acute lymphoblastic leukemia, allergic reaction, Map Kinase, Map Kinase Kinase, D-ras-2, B lymphocyte, signaling process, Medicine, B cell acute lymphocytic leukaemia, dSor1, Neurofibromatosis Type 3, B-cell acute lymphocytic leukaemia, CG1799, single organism signaling, PD0325901, Relapse, l(3)s1747, B acute lymphoblastic leukemia, Ras2, RAS2, SAPKK4, sor/MEK1, B Lymphocytes, Ras1, RAS1, D-sor-1, Ki-ras, acute B cell lymphocytic leukaemia, CG8318, DSor, DRODSOR1, Acute onset, Recrudescence, Personalized Medicine, MAPK, Recklinghausen's disease, Relative Risks, dRas85D, MAP Kinase Kinases, p21[Ras1], DMEK-1, dRas1, dRAS1, ras1, dNF1, Dras85D, ras2, Mitogen Activated Protein Kinase Kinase, dSor, ras-2, BcDNA:RE36103, child, EK1-1, Neurofibromatosis Type 3s, B-ALL, neurofibromatosis type IV, l(1)G0351, LD02673, MAP ERK Kinase, Risk, DmelCG1799, c-Ha-ras, D-ras1, l(1)G0238, D-ras2, trametinib, Hras-1, C-ras1, Dm Ras1, Dras64B, Type 3, PD 0325901, Children, C-ras2, l(3)06677, loss of, l(1)G0002, dMEK, Multiple, RasI, l(1)G0482, Syndromes, Patient, MAPK-ERK, antagonists and inhibitors, Specificity and Sensitivity, B-Lymphocyte, c-H-ras, l(1)G0127, Theranostics, Dsor, Multiple Neurofibromas, WSS, acute B cell lymphocytic leukemia, neurofibromatosis type 2, GSK1120212, Harvey-ras, MAPK Kinase, "Neurofibromatosis (morphologic abnormality)" EXACT [SNOMEDCT_2005_07_31:81669005], accessory, Hras1, MAPK Kinases, "neurofibromatosis" EXACT [CSP2005:2012-7338], MEKs, biological signaling, MAPKK7, neurofibromatosis type 4, "Neurofibromatosis" EXACT [SNOMEDCT_2005_07_31:154642000], JTP-74057, young adult, RasV12, Multiple Neurofibroma, dRas, MAPK-ERK Kinase, Kras2, CG1167, H-ras, DRAS1, acute lymphoblastic leukaemia, DRas2, "Neurofibromatosis" EXACT [NCI2004_11_17:C6727], DmelCG9375, IMPDH, neurofibromatosis, PD-0325901, B-cell lymphoblastic leukemia, supernumerary, LD06825, D-mek, Dras2, Dras1, l(1)G0388, D-Ras, B-cell type acute leukaemia, sensitive, JTP 74057, Dmek, Kras-2, Precision, IMPdH, JNKK2, juvenile, Ha-ras, l(1)G0380, sensitivity, CG15793, MAP, Map, Dras, p21B, Neurofibromatosis 3s, ras 1, B-cell, MAPK ERK Kinase, dras1, Dm-ras-64B, Individualized, MAPKKs, Recrudescences, raspberry/impd, MKK7, inhibiteur, MEK 7, Nf-1, NFNS, Ras[V12], D-sor, Neurofibromas, l(1)G0391, EK3-4, VRNF, B-cell acute lymphocytic leukemia, DRas, DRas85D/Ras, juvenile stage, Ras 85D, Dmras64B, inhibidor, Kinase Kinase, Clients, Syndrome, Sensitivity, ras-l, SOR, Sor, Predictive, NF1, NF-1, nf1, von Reklinghausen disease, D-Mek, D-MEK, B-cell acute lymphoblastic leukemia., l(1)G0056, ALL, inhibitors, GSK 1120212, B cell acute lymphocytic leukemia, Mitogen-Activated Protein Kinase Kinase, MAP-ERK, CG9375, Predictive Medicine, B-cell type acute leukemia, inhibitor, K-ras, sor, function, D-ras-1, Personalized, Client, Cell, MK, E(faf), neurofibromatosis type 1 microdeletion syndrome, MEK/Dsor1, GSK-1120212, DmelCG1167, fs(3)05703, Cytokine, MAPK ERK Kinases, EP(X)1093, S35097, MEK, Mek, MAP Kinase, Neurofibromatosis 3, AI929937, acute lymphocytic leukaemia, Relative Risk, D-SOR, D-Sor, antagonists, DmelCG15793, acute B-cell lymphocytic leukaemia, RAS85D, Dmras85D, MAPKK, l(1)9Eb, Mitogen Activated Protein Kinase Kinases, Kinases, increased number, Neurofibromatosis Syndrome, Risks, mek, Specificity, SAPKK-4, Von Recklinghausen disease, Bursa-Equivalent Lymphocyte, patient, Theranostic, Su(tor)3-2, signalling, present in greater numbers in organism, "Neurofibromatosis syndrome (disorder)" EXACT [SNOMEDCT_2005_07_31:19133005], signalling process, P-Health, PD 325901, AW494271, P Health, PD-325901, B-lymphocyte, NeurofibromafalseCase Report: Precision medicine target revealed by in-vitro modelling of relapsed, refractory ALL from a child with neurofibromatosisChildren with neurofibromatosis have a higher risk of developing juvenile myelomonocytic leukaemia and acute myeloid leukaemia, but rarely develop B-cell acute lymphoblastic leukaemia (B-ALL). Through in-vitro modelling, a novel NF1 p.L2467 frameshift (fs) mutation identified in a relapsed/refractory Ph-like B-ALL patient with neurofibromatosis demonstrated cytokine independence and increased RAS signalling, indicative of leukaemic transformation. Furthermore, these cells were sensitive to the MEK inhibitors trametinib and mirdametinib. Bi-allelic NF1 loss of function may be a contributing factor to relapse and with sensitivity to MEK inhibitors, suggests a novel precision medicine target in the setting of neurofibromatosis patients with B-ALL.2022-04-08 10:22:21EGAS000010061879606EGAD00001008702EGAC00001002637