G2Cdb::Human Disease report

Disease id
D00000089
Name
Childhood acute lymphoblastic leukaemia
Nervous system disease
no

Genes (2)

Gene Name/Description Mutations Found Literature Mutations Type Genetic association?
G00000031 HRAS
v-Ha-ras Harvey rat sarcoma viral oncogene homolog
Y (16533526) Unknown (?) Y
G00001453 PTPN11
protein tyrosine phosphatase, non-receptor type 11
Y (14982869) Microinsertion (MI) Y
G00001453 PTPN11
protein tyrosine phosphatase, non-receptor type 11
Y (16533526) Microinsertion (MI) Y

References

  • PTPN11, RAS and FLT3 mutations in childhood acute lymphoblastic leukemia.

    Yamamoto T, Isomura M, Xu Y, Liang J, Yagasaki H, Kamachi Y, Kudo K, Kiyoi H, Naoe T and Kojma S

    Departments of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan. tomotomo@med.nagoya-u.ac.jp

    PTPN11, the gene which encodes protein tyrosine phosphatase SHP-2, plays an important role in regulating intracellular signaling. Germline mutations in PTPN11 were first observed in Noonan syndrome, while somatic mutations were identified in hematological myeloid malignancies. Recently, PTPN11 mutations have been reported in children with acute lymphoblastic leukemia (ALL). In the present study, we investigated the prevalence of mutations in PTPN11, RAS and FLT3 in samples from 95 Japanese children with ALL. We observed exon 3 and 8 missense mutations of PTPN11 in 6 children with B precursor ALL. One patient with Down syndrome and ALL had PTPN11 mutation. We also identified RAS mutations in ten patients and FLT3 internal tandem duplication (FLT3/ITD) in one patient. None of the patients had simultaneous mutations in PTPN11 and RAS, while one patient had both PTPN11 and FLT3 mutations. These data suggest that PTPN11 mutation may play an important role for leukemogenesis in a proportion of children with ALL, particularly B precursor ALL.

    Leukemia research 2006;30;9;1085-9

  • Genetic evidence for lineage-related and differentiation stage-related contribution of somatic PTPN11 mutations to leukemogenesis in childhood acute leukemia.

    Tartaglia M, Martinelli S, Cazzaniga G, Cordeddu V, Iavarone I, Spinelli M, Palmi C, Carta C, Pession A, Aricò M, Masera G, Basso G, Sorcini M, Gelb BD and Biondi A

    Dipartimento di Biologia cellulare e Neuroscienze, Istituto Superiore di Sanità, Viale Regina Elena, 299-00161 Rome, Italy. mtartaglia@iss.it

    SHP-2 is a protein tyrosine phosphatase functioning as signal transducer downstream to growth factor and cytokine receptors. SHP-2 is required during development, and germline mutations in PTPN11, the gene encoding SHP-2, cause Noonan syndrome. SHP-2 plays a crucial role in hematopoietic cell development. We recently demonstrated that somatic PTPN11 mutations are the most frequent lesion in juvenile myelomonocytic leukemia and are observed in a smaller percentage of children with other myeloid malignancies. Here, we report that PTPN11 lesions occur in childhood acute lymphoblastic leukemia (ALL). Mutations were observed in 23 of 317 B-cell precursor ALL cases, but not among 44 children with T-lineage ALL. In the former, lesions prevalently occurred in TEL-AML1(-) cases with CD19(+)/CD10(+)/cyIgM(-) immunophenotype. PTPN11, NRAS, and KRAS2 mutations were largely mutually exclusive and accounted for one third of common ALL cases. We also show that, among 69 children with acute myeloid leukemia, PTPN11 mutations occurred in 4 of 12 cases with acute monocytic leukemia (FAB-M5). Leukemia-associated PTPN11 mutations were missense and were predicted to result in SHP-2 gain-of-function. Our findings provide evidence for a wider role of PTPN11 lesions in leukemogenesis, but also suggest a lineage-related and differentiation stage-related contribution of these lesions to clonal expansion.

    Funded by: NHLBI NIH HHS: HL71207; NICHD NIH HHS: HD01294

    Blood 2004;104;2;307-13

Literature (2)

Pubmed - human_disease

  • PTPN11, RAS and FLT3 mutations in childhood acute lymphoblastic leukemia.

    Yamamoto T, Isomura M, Xu Y, Liang J, Yagasaki H, Kamachi Y, Kudo K, Kiyoi H, Naoe T and Kojma S

    Departments of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan. tomotomo@med.nagoya-u.ac.jp

    PTPN11, the gene which encodes protein tyrosine phosphatase SHP-2, plays an important role in regulating intracellular signaling. Germline mutations in PTPN11 were first observed in Noonan syndrome, while somatic mutations were identified in hematological myeloid malignancies. Recently, PTPN11 mutations have been reported in children with acute lymphoblastic leukemia (ALL). In the present study, we investigated the prevalence of mutations in PTPN11, RAS and FLT3 in samples from 95 Japanese children with ALL. We observed exon 3 and 8 missense mutations of PTPN11 in 6 children with B precursor ALL. One patient with Down syndrome and ALL had PTPN11 mutation. We also identified RAS mutations in ten patients and FLT3 internal tandem duplication (FLT3/ITD) in one patient. None of the patients had simultaneous mutations in PTPN11 and RAS, while one patient had both PTPN11 and FLT3 mutations. These data suggest that PTPN11 mutation may play an important role for leukemogenesis in a proportion of children with ALL, particularly B precursor ALL.

    Leukemia research 2006;30;9;1085-9

Pubmed - other

  • Genetic evidence for lineage-related and differentiation stage-related contribution of somatic PTPN11 mutations to leukemogenesis in childhood acute leukemia.

    Tartaglia M, Martinelli S, Cazzaniga G, Cordeddu V, Iavarone I, Spinelli M, Palmi C, Carta C, Pession A, Aricò M, Masera G, Basso G, Sorcini M, Gelb BD and Biondi A

    Dipartimento di Biologia cellulare e Neuroscienze, Istituto Superiore di Sanità, Viale Regina Elena, 299-00161 Rome, Italy. mtartaglia@iss.it

    SHP-2 is a protein tyrosine phosphatase functioning as signal transducer downstream to growth factor and cytokine receptors. SHP-2 is required during development, and germline mutations in PTPN11, the gene encoding SHP-2, cause Noonan syndrome. SHP-2 plays a crucial role in hematopoietic cell development. We recently demonstrated that somatic PTPN11 mutations are the most frequent lesion in juvenile myelomonocytic leukemia and are observed in a smaller percentage of children with other myeloid malignancies. Here, we report that PTPN11 lesions occur in childhood acute lymphoblastic leukemia (ALL). Mutations were observed in 23 of 317 B-cell precursor ALL cases, but not among 44 children with T-lineage ALL. In the former, lesions prevalently occurred in TEL-AML1(-) cases with CD19(+)/CD10(+)/cyIgM(-) immunophenotype. PTPN11, NRAS, and KRAS2 mutations were largely mutually exclusive and accounted for one third of common ALL cases. We also show that, among 69 children with acute myeloid leukemia, PTPN11 mutations occurred in 4 of 12 cases with acute monocytic leukemia (FAB-M5). Leukemia-associated PTPN11 mutations were missense and were predicted to result in SHP-2 gain-of-function. Our findings provide evidence for a wider role of PTPN11 lesions in leukemogenesis, but also suggest a lineage-related and differentiation stage-related contribution of these lesions to clonal expansion.

    Funded by: NHLBI NIH HHS: HL71207; NICHD NIH HHS: HD01294

    Blood 2004;104;2;307-13

© G2C 2014. The Genes to Cognition Programme received funding from The Wellcome Trust and the EU FP7 Framework Programmes:
EUROSPIN (FP7-HEALTH-241498), SynSys (FP7-HEALTH-242167) and GENCODYS (FP7-HEALTH-241995).

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