Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.11 (CD10)
 9,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The leukemias of infancy, characterized by an equal distribution of lymphoid and myeloid subtypes, account for 2.5-5% of the acute lymphoblastic leukemias (ALL) and 6-14% of the acute myeloid leukemias (AML) of childhood. Rearrangements of the MLL gene on chromosome 11q23 are the most common genetic abnormalities in both ALL and AML, occurring in 70-80% and approximately 60% of cases, respectively. Infants with ALL and a rearrangement of MLL typically present with hyperleukocytosis, massive organomegaly, CNS involvement, CD10- B-lineage phenotype and myeloid-associated antigen (CD15) expression. Prognosis in these cases is uniformly poor, whereas in similar cases without the genetic defect, it is good to intermediate. The presenting features of infant AML include monoblastic or myelomonoblastic morphology, hyperleukocytosis and extramedullary involvement. Expected outcome approximates that for ALL (approximately 30% long-term survival rate). Rare congenital forms of lymphoid or myeloid leukemia, manifested at birth or during the first month of life, carry a dismal prognosis, especially when a MLL/11q23 rearrangement is present; such cases should be carefully distinguished by chromosomal/molecular analysis and cell culture techniques from transient myeloproliferative disorders which require only supportive care but close follow-up for subsequent development of leukemia. Juvenile chronic myeloid leukemia also can occur in infants and may be responsive to chemotherapy alone. Rapid progress has been made over the past decade in understanding the biology of infant leukemias. The biggest challenge now is to develop more effective treatment, especially for patients with MLL rearrangements.
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PMID:Biology and treatment of infant leukemias. 776 37

We studied a patient with juvenile chronic myelogenous leukemia (JCML) whose terminal course was characterized by transformation to acute lymphoblastic leukemia. Karyotypic studies identified monosomy 7 in leukemic myelomonocytic marrow cells during the chronic phase and in the lymphoblasts during the transformation phase. Our ability to sustain the transformed lymphoblasts in culture allowed us to characterize them further. CD19, HLA-DR, and CD10 were present, consistent with a pre-B acute lymphoblastic leukemia phenotype. CD14 (My-4) and CD13 (My-7) were negative. Rearrangement of immunoglobulin heavy- and light-chain genes identified monoclonal populations of cells of the B lineage. This case provides further evidence that JCML is a clonal disease of pluripotent stem-cell origin.
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PMID:Lymphoid blast crisis of B-lineage phenotype with monosomy 7 in a patient with juvenile chronic myelogenous leukemia (JCML). 818 49

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.
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PMID:Genetic evidence for lineage-related and differentiation stage-related contribution of somatic PTPN11 mutations to leukemogenesis in childhood acute leukemia. 1498 69

Ras-associated autoimmune leukoproliferative disorder (RALD) is a chronic, nonmalignant condition that presents with persistent monocytosis and is often associated with leukocytosis, lymphoproliferation, and autoimmune phenomena. RALD has clinical and laboratory features that overlap with those of juvenile myelomonocytic leukemia (JMML) and chronic myelomonocytic leukemia (CMML), including identical somatic mutations in KRAS or NRAS genes noted in peripheral blood mononuclear cells. Long-term follow-up of these patients suggests that RALD has an indolent clinical course whereas JMML is fatal if left untreated. Immunophenotyping peripheral blood from RALD patients shows characteristic circulating activated monocytes and polyclonal CD10(+) B cells. Distinguishing RALD from JMML and CMML has implications for clinical care and prognosis.
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PMID:JMML and RALD (Ras-associated autoimmune leukoproliferative disorder): common genetic etiology yet clinically distinct entities. 2569 Nov 60